Sex differences in hippocampal slice excitability: role of testosterone.
In vivo fluctuations in gonadal hormones alter hippocampal excitability and modulate both physiological and pathological hippocampal processes. To assess hormonal effects on excitability within a functional hippocampal circuit, extracellular CA1 field responses were compared in slices from intact male, intact female, orchidectomized male, and ovariectomized female rats. Secondly, the effects of in vitro applications of 17-beta estradiol, progesterone, or testosterone on baseline excitability of slices from gonadectomized rats were assessed versus pre-hormone baseline measures. Finally, using the in vitro kindling model of slice epileptogenesis, steroid hormone effects on interictal-like activity were also examined. Significant sex differences in excitatory postsynaptic potential amplitude were observed, with slices from males having larger excitatory postsynaptic potential amplitudes than those from females. Gonadectomy significantly decreased excitatory postsynaptic potential amplitude in slices from male rats. Slices from gonadectomized male and female rats also showed a decreased dendritic excitatory postsynaptic potential slope relative to slices from intact male and females rats. In vitro application of testosterone significantly increased excitatory postsynaptic potential amplitudes in slices from both orchidectomized males and ovariectomized females and the population spike amplitude of slices from ovariectomized females. Following in vitro kindling, slices from intact males showed greater spontaneous burst rates than slices from intact females, further suggesting an excitatory effect of testosterone. These results suggest: (1) a sex difference in the level of baseline excitability between slices from intact males and females as measured by excitatory postsynaptic potential amplitudes, (2) testosterone has excitatory effects on baseline physiology and kindled hippocampal responses, and (3) slices from males show a greater level of excitability than those from females in the in vitro kindling model.


Molecular cloning of DNA from specific chromosomal regions by microdissection and sequence-independent amplification of DNA.
A method that permits the in vitro amplification and cloning of DNA dissected from specific regions of a chromosome and does not require prior knowledge of the DNA sequence is described. DNA from several different chromosomal loci in the Drosophila melanogaster genome has been isolated by this method. Although the procedure was developed to permit the isolation of DNA sequences from serial sections of a single microdissected polytene chromosome, it should be useful for obtaining DNA clones from specific regions of the nonpolytene chromosomes of other organisms as well.


Effect of short-term exposure to air pollution on COVID-19 mortality and morbidity in Iranian cities.
The association between air pollutant (PM2.5, PM10, NO2, and O3) concentrations and daily number of COVID-19 confirmed cases and related deaths were evaluated in three major Iranian cities (Tehran, Mashhad, and Tabriz). Hourly concentrations of air pollutants and daily number of PCR-confirmed cases and deaths of COVID-19 were acquired (February 20th, 2020 to January 4th, 2021). A generalized additive model (GAM) assuming a quasi-Poisson distribution was used to model the associations in each city up to lag-day 7 (for mortality) and 14 (for morbidity). Then, the city-specific estimates were meta-analyzed using a fixed effect model to obtain the overall relative risks (RRs). A total of 114,964 confirmed cases and 21,549 deaths were recorded in these cities. For confirmed cases, exposure to PM2.5, NO2, and O3 for several lag-days showed significant associations. In case of mortality, meta-analysis estimated that the RRs for PM2.5, PM10, NO2, and O3 concentrations were 1.06 (95% CI: 0.99, 1.13), 1.06 (95% CI: 0.93, 1.19), 1.15 (95% CI: 0.93, 1.38), and 1.07 (95% CI: 0.84, 1.31), respectively. Despite several positive associations with all air pollutants over multiple lag-days, COVID-19 mortality was only significantly associated with NO2 on lag-days 0-1 and 1 with the RRs of 1.35 (95% CI: 1.04, 1.67) and 1.16 (95% CI: 1.02, 1.31), respectively. This study showed that air pollution can be a factor exacerbating COVID-19 infection and clinical outcomes. Actions should be taken to reduce the exposure of the public and particularly patients to ambient air pollutants. The online version contains supplementary material available at 10.1007/s40201-021-00736-4.


[Psychological support for weight loss].
Psychological support for obese people as part of their health care process seems to be a matter of course. However, it is one of the most poorly relayed components in the field. Exploring and assessing are necessary operations in order to develop an integrative approach to psychological support, involving body-mediated approaches and an optimal helping alliance.


False positive staining in the TUNEL assay to detect apoptosis in liver and intestine is caused by endogenous nucleases and inhibited by diethyl pyrocarbonate.
The terminal transferase uridyl nick end labelling (TUNEL) assay allows the easy demonstration of cell death as a result of apoptosis. However, when this assay is applied to liver tissue, the number of TUNEL positive cells is dependent on the time of incubation with proteinase K. To test whether false positive results are the result of the release of endogenous endonucleases by proteinase K and can be abolished by pretreatment with diethyl pyrocarbonate (DEPC). Involution of hyperplastic ductules in bile duct ligated rats after biliary decompression by Roux-en-Y anastomosis and acute CCl4 intoxication were studied as models of apoptosis and necrosis, respectively. A standard TUNEL assay was applied to formalin fixed tissue sections mounted with cement. To inhibit putative endogenous endonucleases, tissue slides were pre-incubated with DEPC. In the standard TUNEL assay, the number of positive nuclei was highly dependent upon the length of time that sections were incubated with proteinase K. After pretreatment with DEPC, only cells that also exhibited morphological features of apoptosis stained positive. DEPC pretreatment abolished false positive staining in CCl4 induced hepatocyte necrosis and blocked interference by endogenous alkaline phosphatase in intestine. The method of gluing the tissue section to the glass slide was found to be of utmost importance because the effect of DEPC was abolished on silanised slides. False positive staining in the TUNEL assay in the liver is caused by the release of endogenous endonucleases as a result of proteinase treatment. This can be abolished by pretreatment of tissue slides with DEPC.


Patency and limb salvage rates after distal revascularization to unclampable calcified outflow arteries.
Severe circumferential calcification of the outflow artery during lower-extremity distal revascularization is considered a poor prognostic factor for bypass graft patency. The aim of this study was to assess the influence of circumferential infrapopliteal arterial calcification on bypass graft patency and limb salvage rates, comparing patency and limb salvage rates in unclampable calcified distal outflow arteries with those observed in uncalcified distal outflow arteries. From July 1990 to July 1997, of 441 distal bypass graft procedures performed by the same surgeon, 69 (16%, group I) involved unclampable calcified outflow vessels, whereas 83 (19%, group II) outflow vessels were uncalcified; the other 289 (65%) had varying intermediate degrees of calcification and were not included in this analysis. All procedures were performed for limb-threatening ischemia and involved standard vein patch angioplasty of the distal anastomotic site, irrespective of the conduit used. Primary and secondary patency, limb salvage, and survival rates were assessed by using Kaplan-Meier analysis. Groups were similar with regard to age, sex, and atherosclerotic risk factors except for a higher incidence of diabetes mellitus (88% vs 65%, P =.001) and renal failure (17% vs 5%, P =.01), including dialysis dependency (P =.01) in group I. Gangrene as an indication for surgery was statistically more frequent in group I (49% vs 29%, P =.01). The distal anastomotic locations and types of conduit involved were similar in the two groups. The femoral inflow level was used more often in group II (63% vs 38%, P =.003), the popliteal in group I (32% vs 17%, P =.03). Follow-up ranged from 30 days to 144 months, with a mean of 69 months. None of the patients were lost during the follow-up period. None of the patients died during the perioperative (30-day) period. Primary patency rates at 1, 3, and 5 years were 84%, 65%, and 52% for group I and 89%, 76%, and 69% for group II (P =.07.). Secondary patency rates at 1, 3, and 5 years were 96%, 82%, and 78% for group I and 96%, 85%, and 82% for group II (P =.58). Limb salvage rates at 1, 3, and 5 years were 93%, 83%, and 81% for group I and 97%, 90%, and 86% for group II (P =.39). Distal revascularization to unclampable, severely calcified outflow arteries can achieve much the same results to those obtained in uncalcified outflow arteries. A circumferentially calcified distal recipient artery should not be considered a major obstacle to an attempt at limb salvage bypass graft surgery.


A photosynthetic rotating annular bioreactor (Taylor-Couette type flow) for phototrophic biofilm cultures.
In their natural environment, the structure and functioning of microbial communities from river phototrophic biofilms are driven by biotic and abiotic factors. An understanding of the mechanisms that mediate the community structure, its dynamics and the biological succession processes during phototrophic biofilm development can be gained using laboratory-scale systems operating with controlled parameters. For this purpose, we present the design and description of a new prototype of a rotating annular bioreactor (RAB) (Taylor-Couette type flow, liquid working volume of 5.04 L) specifically adapted for the cultivation and investigation of phototrophic biofilms. The innovation lies in the presence of a modular source of light inside of the system, with the biofilm colonization and development taking place on the stationary outer cylinder (onto 32 removable polyethylene plates). The biofilm cultures were investigated under controlled turbulent flowing conditions and nutrients were provided using a synthetic medium (tap water supplemented with nitrate, phosphate and silica) to favour the biofilm growth. The hydrodynamic features of the water flow were characterized using a tracer method, showing behaviour corresponding to a completely mixed reactor. Shear stress forces on the surface of plates were also quantified by computer simulations and correlated with the rotational speed of the inner cylinder. Two phototrophic biofilm development experiments were performed for periods of 6.7 and 7 weeks with different inoculation procedures and illumination intensities. For both experiments, biofilm biomasses exhibited linear growth kinetics and produced 4.2 and 2.4 mg cm(-)² of ash-free dry matter. Algal and bacterial community structures were assessed by microscopy and T-RFLP, respectively, and the two experiments were different but revealed similar temporal dynamics. Our study confirmed the performance and multipurpose nature of such an innovative photosynthetic bioreactor for phototrophic biofilm investigations.


Dissolution behaviors of a visible-light-responsive photocatalyst BiVO4: Measurements and chemical equilibrium modeling.
Despite of the extensive research in semiconductor photocatalysis with respect to material and device innovations, much of the fundamental aquatic chemistry of those new materials that governs their environmental hazard and implications remains poorly understood. BiVO4 has long been recognized as a promising visible-light-responsive photocatalyst. However, the solubility product (Ksp) of BiVO4 and the mechanistic understanding of the non-stoichiometric dissolution of BiVO4 remain unclear. Here, we investigated the solubility of BiVO4 via the observation on its non-stoichiometric dissolution in the pH range of 4-9. Combining dissolution experiments, adsorption behavior and thermodynamic equilibrium calculations, the Ksp of BiVO4 was determined to be 10-35.81±0.51. The solubility and stability of BiVO4 were strongly pH-dependent, with the lowest solubility and highest stability near pH 5. Furthermore, we tested the effect of illumination on the dissolution of BiVO4, which was significantly enhanced by light. Under both dark and illumination conditions, adsorption of dissolved bismuth by BiVO4 solids was the main reason for the non-stoichiometric dissolution of BiVO4, and could be modeled by including an additional surface complexation reaction. Thus, the results highlighted the importance of considering the dissolution of photocatalysts, and presented a feasible method to evaluate environmental stability and risks of other semiconductor materials.


Serotypes in Cowdria ruminantium and their relationship with Ehrlichia phagocytophila determined by immunofluorescence.
Two tick-borne rickettsial pathogens of ruminants, Cowdria ruminantium (causative agent of heartwater disease) and Ehrlichia phagocytophila (causative agent of tick-borne fever), were successfully cultivated in caprine or ovine neutrophilic granulocytes. Infected cultures were subsequently used as antigens in the indirect fluorescent antibody test. Low-level bilateral serological cross-reactions could be detected between Cowdria and Ehrlichia. In addition, comparison of five Cowdria stocks using immunofluorescence demonstrated the existence of distinct serotypes within the genus of Cowdria. It is concluded that the occurrence of these serotypes will considerably complicate the current serodiagnosis of heartwater.


Childhood psychological maltreatment, optimism, aversion to happiness, and psychological adjustment among college students.
Although there is increasing empirical evidence of the negative impact of childhood maltreatment on adult mental health and well-being, little is known about the underlying factors that mitigate the link between psychological maltreatment and psychological adjustment. A critical step is to examine these mechanisms to develop prevention and intervention strategies to decrease the adverse impacts of child maltreatment on psychological adjustment and well-being among young adults. The presented study aimed to explore the association between childhood psychological maltreatment and young adults' psychological adjustment through aversion to happiness, optimism, and pessimism. The sample of this study comprised 511 college students. Participants included 64% female, with ranging in age between 18 and 39 years (M = 21.36, SD = 2.55). Findings from the study indicated that aversion to happiness was a significant mediator in the association of psychological maltreatment with pessimism, optimism, and psychological adjustment. Further, optimism and pessimism mitigated the link of both aversion to happiness and psychological maltreatment with psychological adjustment. The findings indicate that optimism-based strategies are key to fostering psychological adjustment and could help to reduce the negative impacts of aversion to happiness and child maltreatment on young adults' adjustment and wellbeing.


Temperature effects on the rheological properties of current polyether and polysiloxane impression materials during setting.
Rheological tests of elastomeric impression materials during setting have been most often conducted at room temperature rather than at intraoral temperature. Because temperature may affect properties and the setting kinetics, clinically relevant inferences may not be accurate with studies conducted at room temperature. The purpose of this study was to determine the viscoelastic properties of new low- and medium-viscosity elastomeric impression materials during setting at 33 degrees C and to evaluate the medium-viscosity materials at 3 additional temperatures. The impression materials investigated at 33 degrees C were 2 polyvinylsiloxanes (PVS) (Aquasil Deca and Aquasil LV) and 5 polyethers (PE) (Impregum Penta, Impregum Penta Soft H, Impregum Penta Soft L, Impregum Garant Soft L, and Permadyne Garant L). Three impression materials (Aquasil Deca, Impregum Penta, and Impregum Penta Soft H) were also investigated at 25 degrees, 29 degrees, and 37 degrees C. Time-dependent oscillatory rheometry was carried out on these materials (n=3) with a rheometer with a 25-mm diameter parallel plate cell. The storage modulus (G') and the loss tangent (tandelta) were determined as functions of time over a period from 0 seconds to 900 seconds, commencing 40 seconds after mixing. Induction time (t(ind)) or initial setting time and tandelta, the relative liquidlike behavior, were also computed. A single-factor analysis of variance (ANOVA) was used for the properties determined at 33 degrees C and a 2-factor ANOVA was used for the temperature studies, with hypothesis testing at alpha=.05. The G'(t) curves for all materials displayed the expected sigmoidal shape with time, with the solid-like behavior rising slowly, then more rapidly, and again slowly to final set. The initial setting time (t(ind)) was found to be approximately 2.8 minutes for the PVS materials and for Impregum Penta and Impregum Penta Soft H, but was significantly longer for the remaining 3 PE low viscosity materials. The solid-like behavior (G') at final set or shear modulus differed among all materials, ranging from 1.0 MPa for Aquasil Decca, 1.69 for Impregum Penta Soft H, and 1.8 MPa for Impregum Penta. G' for low-viscosity materials ranged from 0.66 MPa for Aquasil LV and 0.79 MPa for Permadyne Garant L to 1.2 MPa for Impregum Penta Soft L. The loss tangent at 40 seconds tandelta (t(0)) varied among medium and low viscosity materials, ranging from liquid-like behavior of 4.3 for Permadyne Garant and less than unity or significant solid-like behavior for Impregum Penta. All materials showed tandelta values less than unity at their setting times. The temperature studies revealed significant changes in the kinetics of setting, with the setting time decreasing more than 3-fold between 25 degrees and 37 degrees C for the Aquasil Deca and the Impregum Penta Soft H and more than 2-fold for the Impregum Penta. At room temperature of 25 degrees C, the storage modulus for Impregum Penta Soft H and Aquasil Deca was 1.1% and 37.5% lower than Impregum Penta, respectively. The development of the viscoelastic rheological properties with time for 3 medium- and 4 low-viscosity impression materials at 33 degrees C showed significant differences in the setting time and the magnitude of the storage modulus. Compared with Impregum Penta, the new Impregum Penta Soft H was 6% less stiff when set, compared with 44% lower stiffness for the medium viscosity addition silicone. Temperature studies between 25 degrees C and 37 degrees C revealed strong temperature sensitivity of the kinetics of setting and evolution with time of their rheological properties.


Geographic differences of pacemaker implant rates in Europe.
Pacemaker therapy, which has proved to be the only treatment for symptomatic bradyarrhythmias, exhibits great variation from country to country around the world. The aim of this study was to examine the variations in the number of first implants per calendar year in different European countries and to relate the differences to certain socioeconomic indices. Information concerning new pacemaker implants during the year 1999 was obtained from the European Pacemaker Registry, which is maintained by the Working Group of Cardiac Pacing of the European Society of Cardiology. Comparisons of pacemaker and econometric indices between western and eastern Europe were carried out using the t-test. Correlations between selected pacemaker parameters and econometric indices were examined using univariate and multivariate regression analysis. Our findings reveal significant geographic differences in both the number of first implants and the types of pacemaker implanted. The gross domestic product is strongly related to the number of new pacemaker implants per year, as well as the number of pacing centers in individual countries. Significant geographic variations exist within Europe as to the number of annual pacemaker implants and the types of pacemakers implanted. These variations are related to specific economic indices in the countries concerned.


Quantitative neurodegenerative pathology does not explain the degree of hippocampal atrophy on MRI in degenerative dementia.
The purpose of this study was to investigate the neuropathological substrates underlying in vivo hippocampal atrophy on magnetic resonance imaging (MRI) in autopsy confirmed neurodegenerative dementia cases. Thirty-one neuropathologically verified cases (23 with Lewy body dementia (LBD) and eight with Alzheimer's disease (AD)) were included who had undergone an MRI scan close to death (mean 1.5 years). Manual volumetric measurements were undertaken for the hippocampus, entorhinal cortex and amygdala on MRI, along with quantitative neuropathological analysis of plaque, tangle and Lewy body pathology in the same regions. The relationship between neuropathology and MRI volumes was assessed using correlations and linear regression. Hippocampal and amygdala volumes were significantly smaller in cases with AD than with LBD, but there was no difference in entorhinal cortex volume. Analysing all cases together, a significant positive correlation was observed between normalised hippocampal volume and percent area of Lewy bodies in the hippocampus (r=0.449, p=0.017) but not with tangles (r=0.059, p=0.766) or plaques (r=-0.361, p=0.119). There were no other significant correlations between regional MRI volume and measures of neuropathology. Regression analysis showed that overall diagnosis of AD rather than burden of individual pathological changes was the most significant predictor of hippocampal volume loss in autopsy confirmed cases. Our results suggest that (i) hippocampal and amygdala but not entorhinal cortex, volumes differ between AD and LBD and (ii) factors other than current markers of neurodegenerative pathological change are responsible for atrophy of medial temporal lobe structures in AD and LBD.


Modulation of an RGDS binding site on the platelet membrane glycoprotein IIb-IIIa complex.
Fibronectin, von Willebrand factor, and fibrinogen each bind to the glycoprotein IIb-IIIa complex on activated platelets via an arg-gly-asp-ser (RGDS) sequence present within the adhesive proteins. Both the IIb and IIIa polypeptides of the IIb-IIIa complex on thrombin activated platelets are specifically and extensively labeled by a radiolabeled, photoactivatable arylazide derivative of the RGDS sequence when the labeling is performed in the presence of concentrations of Ca++ or Mg++ approaching 0.5 mM. In contrast, labeling of unactivated platelets, ADP activated platelets, or thrombin activated platelets in the presence of low concentrations of divalent cations resulted in restriction of labeling to the IIb polypeptide of the complex.


A time-sensitive analysis of the work-crime relationship for young men.
Theories of the work-crime relationship suggest that employment reduces crime by offering routines, income, and supervision. However, selection into and out of jobs could also explain the negative association between work and crime: people may start working when they are already offending less and stop working when they are already offending more. To evaluate these possibilities, I model month-to-month, within-person changes in offending during the periods surrounding job transitions. Using data from the Pathways to Desistance study, I analyze a sample of young, justice-involved men in two U.S. cities, Phoenix and Philadelphia. I find large reductions in income-related offending during the months leading up to job entry, after which there is no further decrease. I also find that offending spikes before job exit. These patterns suggest that for these young men, being employed does not reduce crime. Rather, employment transitions occur in response to other changes in their lives.


Expression and regulation of apolipoprotein E receptors in the cells of the central nervous system in culture: A review.
The importance of apolipoprotein E (apoE) in the central nervous system (CNS) became increasingly clear since the descovery that apoE ε4 allele is a major risk factor for Alzheimer's disease. ApoE is one of the major apolipoproteins that acts as a ligand for the cellular uptake of lipoproteins via apoE receptors, members of low-density lipoprotein receptor (LDLR) family, in the CNS. Recently, LDLR family has been shown to have new functions that modulate intracellular signalling and affect neuronal and glial functions, survival and regeneration. However, the pattern of expression of apoE receptors in the CNS has not been fully clarified yet. The LDLR, very low density lipoprotein receptor (VLDLR), LDLR-related protein (LRP), and apolipoprotein E receptor 2 (apoER2) are known to bind to and internalize apoE-containing lipoproteins. Here we summarize the expression of apoE receptors in the CNS and demonstrate additional our original data on cell type specific expression and regulation of those receptors in the CNS, using in situ hybridization and RT-PCR. The cells used in our study were highly enriched cultures of neurons, astrocytes, microglia and oligodendrocytes isolated from rat brain and neuroblastoma cell line, Neuro2a. All of these four types of receptors were shown to be expressed in neurons, astrocytes, microglia and oligodendrocytes, while LDLR and LRP were expressed in Neuro2a cells. We further examined the regulation of the expression of these receptors by altering the cholesterol content of the cells, and found that only the LDLR expression was downregulated following internalization of lipoprotein cholesterol and upregulated by cholesterol deprivation, in neuronal and astroglial cells. These data together with previous studies suggest that LDLR, VLDL, LRP, and apoER2 may be involved in apoE-mediated lipid uptake and/or intracellualr signalling in the cells of the CNS cells, i.e., neurons, astrocytes, microglia, and oligodendrocytes.


Influence of heart rate at rest for predicting the metabolic syndrome in older Chinese adults.
The aim of this study was to examine the relationship between seated resting heart rate and the metabolic syndrome (MetS) among older residents of Guangzhou, South China. A total of 30,519 older participants (≥50 years) from the Guangzhou Biobank Cohort Study were stratified into quartiles based on seated resting heart rate. The associations between each quartile and the MetS were assessed using multivariable logistic regression. A total of 6,907 (22.8 %) individuals were diagnosed as having the MetS, which was significantly associated with increasing heart rate quartiles (P < 0.001). Participants in the uppermost quartile (mean resting heart rate 91 ± 8 beats/min) of this cardiovascular proxy had an almost twofold increased adjusted risk (odds ratio (95 % CI) = 1.94 (1.79, 2.11), P < 0.001) for the MetS, as compared to those in the lowest quartile (mean resting heart rate, 63 ± 4 beats/min). Heart rate, which is an inexpensive and simple clinical measure, was independently associated with the MetS in older Chinese adults. We hope these observations will spur further studies to examine the usefulness of resting heart rate as a means of risk stratification in such populations, for which targeted interventions should be implemented.


The "National Integrated Medical Imaging System" [NIMIS]-friend, not nimesis!
The "National Integrated Medical Imaging System" or NIMIS went live in 2011 and allows the movement of patient radiology imaging throughout the Irish health system. At the time of its launch, NIMIS was not only going to allow the filmless passage of patient radiology imaging but it was also envisaged that it would act as a medical image archive. The aim of this study was to assess the awareness and use of non-consultant hospital doctors and hospital consultants with regard to this medical image archive/referral function of NIMIS. A survey was carried out on 50 doctors across all specialities and grades at Tullamore Hospital looking at different aspects of the use of NIMIS. Ninety-four percent of respondents use NIMIS on a daily basis and 6% use it on a weekly basis. The primary reason for using NIMIS was found to be "Viewing and Ordering Imaging" in 92% of those surveyed with 8% stating it was "Viewing imaging/reports". Ninety-eight percent surveyed said they had never used NIMIS to send a referral form or clinical photograph and 82% were not aware of this potential function. The majority of those surveyed stated that they either agreed or strongly agreed NIMIS is user-friendly. NIMIS allows the safe and confidential flow of patient images and clinical information in the Irish health system. It could provide definite potential in the areas of clinical conferencing, multidisciplinary meetings and remote patient assessment along with collaborative research and education.


Helicobacter cinaedi-Associated Refractory Cellulitis in Patients with X-Linked Agammaglobulinemia.
X-linked agammaglobulinemia (XLA) is characterized by severe or recurrent infections, hypogammaglobulinemia, and circulating B cell deficiency. The frequent pathogens seen in patients with XLA include Streptococcus pneumoniae, Haemophilus influenzae, Pseudomonas aeruginosa, and enterovirus as well as Campylobacter and Helicobacter species. Here, we describe two patients with XLA who developed cellulitis and bacteremia caused by Helicobacter cinaedi even when administered an appropriate immunoglobulin replacement therapy. H. cinaedi may be difficult to isolate using a conventional blood culture system and could be identified by sequence analysis and mass spectrometry. H. cinaedi infection causes recurrent symptoms frequently, and patients require a long course of antibiotic treatment. Recently, the case of non-H. pylori Helicobacter (NHPH) infection such as H. cinaedi and H. bilis infection is increasing in number in patients with XLA. Systemic NHPH infection should be suspected, and extensive microbiological analysis should be performed to appropriately treat patients with XLA who present with fever and skin lesions.


Further studies of the effect of pepstatin on ascites accumulation in tumor-bearing mice.
Studies were done of the effect of pepstatin on ascites accumulation in mice bearing MM46, Ehrlich, CCM, SN36, L1210, and NTF ascites tumors. When pepstatin was injected subcutaneously at 80 mg/kg body wt before ascites accumulation, it inhibited the accumulation in all strains of the tumors tested. In MM46, CCM and NTF tumor strains there was also a decrease in the tumor cell numbers following pepstatin treatment. Kinetic studies on ascites accumulation with tumor strain MM46 demonstrated that even when pepstatin was injected after ascites accumulation it reduced the ascites volume. A dose-dependent effect was observed in this tumor strain when pepstatin was injected both before and after ascites accumulation. The results confirm previous studies of pepstatin's ability to retard ascites in L1210 and P-815Y ascites tumors and also broaden the concept of the mechanisms by which petstatin may be acting.


Phloretin ameliorates diabetes-induced endothelial injury through AMPK-dependent anti-EndMT pathway.
Diabetic cardiovascular complications contribute more than half of diabetes mortality. Endothelial damage and subsequent pathological changes play a key role in this process. Phloretin, a plant-derived dihydrochalcone compound, was reported to have the activities in regulating metabolism homeostasis and anti-inflammation. However, its effects and the mechanism on early stage endothelial injury caused by diabetes are not clear yet. In our present study, human umbilical vein endothelial cells (HUVECs) were stimulated by high glucose or advanced glycation end products (AGEs) to induce endothelial damage, and streptozotocin (STZ) -induced diabetes mouse model was used for in vivo study. Our results showed that phloretin effectively reduced endothelial damage marker monocyte chemotactic protein-1 (MCP1) as well as pro-calcification factors bone morphogenetic protein-2 (BMP2) and receptor activator of NF-κB ligand (RANKL) expression, reversed the increased vimentin and decreased CD31 dose-dependently in vitro and in vivo. Phloretin had no effect on blood glucose level. However, it ameliorated endothelial injury and vascular fibrosis in diabetic mice. Further experiments revealed that phloretin could enhance AMP activated protein kinase (AMPK) activation and upregulate peroxidase proliferator activated receptor-gamma coactivator-lα (PGC1α) level, and inhibit the activation of TGFβ-Smad2-Snail signalling pathway which was abrogated by AMPK inhibitor, providing a rational mechanism that AMPK activation was required for the effects of phloretin on endothelial injury and endothelial-mesenchymal transformation (EndMT). Our data reveal a new role of phloretin in protection of diabetic endothelial damage via AMPK-dependent anti-EndMT activation, and also provide a potential therapeutic way for diabetic endothelial damage and its subsequent cardiovascular complications.


Self-propelled micro/nanobots: A new insight into precisely targeting cancerous cells through intelligent and deep cancer penetration.
Cancer overlooks are globally one of the most dangerous and life-threatening tribulations. While significant advances have been made in the targeted delivery of anti-cancer medications over the last few years, several challenges, such as low efficacy and strong toxic effects, remain to be addressed. Micro/nanomotors have been thoroughly studied for both effective cancer detection and treatment, as demonstrated by significant advancements in the architecture of smart and functional micro/nanomotor biomedical systems. Able to self-propelled within fluid media, micro/nanomotors have attractive vehicles to maximize the efficacy of tumor delivery. Here, we present the current developments in the delivery, detection, and imaging-guided treatment of micro/nanomotors in the clinical field, including cancer-related specific targeted drug delivery, and then discuss the barriers and difficulties encountered by micro/nanomotors throughout the medical process. Furthermore, this paper addresses the potential growth of micro/nanomotors for medical applications, and sets out the current drawbacks and future research directions for more advancement.


H-2-specific antibodies induced by injection of syngeneic leukemia cells.
AKR/J mice immunized with several syngeneic leukemia cells contained antibodies in their sera which reacted with certain AKR leukemia cell lines, depending on their H-2 expression, and precipitated H-2K antigens from lysates of leukemia cells. Precipitation of H-2K was not due to virus-specific antibodies: it could not be blocked by prior absorption with H-2-negative leukemias, but was blocked by certain allogeneic lymphocytes. Tumor-specific H-2K antibodies did not react with H-2K from normal AKR lymphocytes either on the cell surface or after detergent solubilization; however, they did react with H-2K from mitogen-activated AKR and BALB.K lymphoblasts. Since both these latter cells were also lysed by AKR-Gross/MuLV-specific and H-2Kk-restricted cytotoxic T lymphocytes, we consider the possibility that antibodies detecting conformational alterations induced in H-2Kk molecules by viral association may be present in syngeneic AKR antileukemia sera.


Myoendothelial and placental blood flow responses to ritodrine infusion in the guinea pig.
The effect of ritodrine hydrochloride on uterine blood flow was investigated in near-term guinea pigs. The infusion of ritodrine in doses sufficient to inhibit uterine activity provoked tachycardia, and the cardiac output tended to rise. The percentage of cardiac output reaching the gravid uterus did not alter during the infusion of 12 micrograms per minute of ritodrine but decreased from 12% to 10% when the infusion rate was 120 micrograms per minute. There was an increase in the myoendothelial fraction of cardiac output in both instances, whereas the placental fraction decreased at the higher rate of infusion. Perfusion of the myoendothelial tissue improved during the infusion of 12 or 120 micrograms per minute of ritodrine, increasing by 25% and 18% respectively. No significant alteration occurred in the perfusion of the placental tissue.


Isolation and characterization of a polyamine-peptide conjugate from human amniotic fluid.
Significant amounts of the diamine putrescine and the polyamines spermidine and spermine could be detected in human third-trimester amniotic fluid only after acid hydrolysis. This observation was interpreted to mean that these amines existed only in conjugated form in this biological fluid. Upon fractionation by ultrafiltration 90--10% of the putrescine was associated with the 1000--10 000 dalton fraction. Spermine was identified in this fraction and in a low-molecular weight fraction presumably representing acetylated derivatives. Spermidine was entirely associated with the 10 000--30 000 dalton fraction. The putrescine conjugate was purified to homogeneity by column chromatography on Biogels P10 and P6 followed by ion-exchange chromatography on DEAE-Sephadex A-25. Molecular weight by gel exclusion using peptide standards was estimated to be approx. 4600. The UV absorption spectrum of the putrescine conjugate conformed to that expected for a polypeptide. This putrescine conjugate contained 39 identified amino acids with a combined molecular weight of 4713. Putrescine was detectable by high pressure liquid chromatography only after acid hydrolysis of the conjugate. No other polyamines were detected in these hydrolyzates, nor were any polyamines demonstable in hydrolyzates of control peptides nor in pooled column washes. The identity of the putrescine determined by high pressure liquid chromatography was confirmed by a two-dimensional thin-layer chromatography method. These results establish the in vivo production of a putrescine--polypeptide conjugate in man. Such molecular species may constitute yet another metabolic pathway for polyamines or may reflect another mode of post-translational modification of polypeptide structure and function. The qualitative and quantitative analysis of polyamine conjugate in human aminotic fluid may prove to be useful in the detection of abnormalities in fetal development.


Analysis of peptide uptake and location of root hair-promoting peptide accumulation in plant roots.
Peptide uptake by plant roots from degraded soybean-meal products was analyzed in Brassica rapa and Solanum lycopersicum. B. rapa absorbed about 40% of the initial water volume, whereas peptide concentration was decreased by 75% after 24 h. Analysis by reversed-phase HPLC showed that number of peptides was absorbed by the roots during soaking in degraded soybean-meal products for 24 h. Carboxyfluorescein-labeled root hair-promoting peptide was synthesized, and its localization, movement, and accumulation in roots were investigated. The peptide appeared to be absorbed by root hairs and then moved to trichoblasts. Furthermore, the peptide was moved from trichoblasts to atrichoblasts after 24 h. The peptide was accumulated in epidermal cells, suggesting that the peptide may have a function in both trichoblasts and atrichoblasts.


Supportless electrochemical sensor based on molecularly imprinted polymer modified nanoporous microrod for determination of dopamine at trace level.
In this work, we developed a novel freestanding metallic microrod as working electrode for highly sensitive and selective electrochemical detection of trace dopamine (DA). The electrode was facilely fabricated via first dealloying smooth Au-Ag alloy microrod (AMR) into nanoporous Au-Ag alloy microrod (NPAMR) and further modifying with electro-polymerized molecularly imprinted polymer (MIP). Influencing factors during electro-polymerization process including pH value and molar ratio of monomer to template molecule were optimized. Under the optimal conditions, a linear range from 2 × 10(-13) to 2 × 10(-8)M for measuring DA was obtained with an ultralow detection limit of 7.63 × 10(-14)M (S/N=3). In addition, the MIP-modified electrode (MIP/NPAMR) was successfully employed to test DA in serum and brain samples.


Red circularly polarized luminescence from intramolecular excimers restricted by chiral aromatic foldamers.
Aromatic oligoamide foldamers are highlighted as a verstile paltform for developing single-handed foldamers with two aromatic acetenyl groups at the same side. The foldamers with pyrene acetenyl units exhibit red excimer emissions, which were circularly polarized and show interesting circularly polarized luminescence properties with high CPL brightness BCPL up to 109.8 M-1.cm-1. The red excimer CPL was attributed to the extended conjugations and the spatial restriction of pyrene units at the same side of foldamers.


Simultaneous in situ detection of two mRNAs in the same cell using riboprobes labeled with biotin and 35S.
We used 35S-labeled and biotinylated cRNAs (riboprobes) to detect simultaneously two different mRNAs by in situ hybridization. In a first step we established the conditions under which each type of probe achieved the same high level of sensitivity. We then used these conditions to hybridize BHK cells infected with Theiler's virus, a murine picornavirus, with a mixture of a virus-specific biotinylated riboprobe and a 35S-labeled riboprobe specific for beta-actin mRNA. Both mRNAs could be detected in the same cell, although the sensitivity achieved by the radiolabeled probe was reduced by about 40% by the simultaneous hybridization with the biotinylated probe.


Impact of High-Fidelity Pediatric Simulation on Paramedic Seizure Management.
A simulation-based course, Pediatric Simulation Training for Emergency Prehospital Providers (PediSTEPPs), was developed to optimize pediatric prehospital care. Seizures are common in Emergency Medical Services (EMS), and no studies have evaluated pediatric outcomes after EMS simulation training. The primary objective was to determine if PediSTEPPs enhances seizure protocol adherence in blood glucose measurement and midazolam administration for seizing children. The secondary objective was to describe management of seizing patients by EMS and Emergency Departments (EDs). This is a two-year retrospective cohort study of paramedics who transported 0-18 year old seizing patients to ten urban EDs. Management was compared between EMS crews with at least one paramedic who attended PediSTEPPs and crews that had none. Blood glucose measurement, medications administered, intravenous (IV) access, seizure recurrence, and respiratory failure data were collected from databases and run reports. Data were compared using Pearson's χ(2) test and odds ratios with 95% confidence intervals (categorical) and the Mann-Whitney test (continuous). Of 2200 pediatric transports with a complaint of seizure, 250 (11%) were actively seizing at the time of transport. Of these, 65 (26%) were treated by a PediSTEPPs-trained paramedic. Blood glucose was slightly more likely to be checked by trained than untrained paramedics (OR = 1.35, 95% CI 0.72-2.51). Overall, 58% received an indicated dose of midazolam, and this was slightly more likely in the trained than untrained paramedics (OR = 1.39, 95% CI 0.77-2.49). There were no differences in secondary outcomes between groups. The prevalence of hypoglycemia was low (2%). Peripheral IVs were attempted in 80%, and midazolam was predominantly given by IV (68%) and rectal (12%) routes, with 51% receiving a correct dose. Seizures recurred in 22%, with 34% seizing on ED arrival. Respiratory failure occurred in the prehospital setting in 25 (10%) patients in the study. Simulation-based training on pediatric seizure management may have utility. Data support the need to optimize the route and dose of midazolam for seizing children. Blood glucose measurement in seizure protocols may warrant reprioritization due to low hypoglycemia prevalence. seizure; emergency medical services; simulation; pediatrics.


Lounging with robots--social spaces of residents in care: A comparison trial.
To investigate whether robots could reduce resident sleeping and stimulate activity in the lounges of an older persons' care facility. Non-randomised controlled trial over a 12-week period. The intervention involved situating robots in low-level and high-dependency ward lounges and a comparison with similar lounges without robots. A time sampling observation method was utilised to observe resident behaviour, including sleep and activities over periods of time, to compare interactions in robot and no robot lounges. The use of robots was modest; overall 13% of residents in robot lounges used the robot. Utilisation was higher in the low-level care lounges; on average, 23% used the robot, whereas in high-level care lounges, the television being on was the strongest predictor of sleep. This study found that having robots in lounges was mostly a positive experience. The amount of time residents slept during the day was significantly less in low-level care lounges that had a robot.


Effects of age and strain on the microbiota colonization in an infant human flora-associated mouse model.
The establishment of human flora-associated animal models allows the in vivo manipulation of host, microbial, and environmental parameters to influence the gut microbial community. However, it is difficult to simulate infant gut microbiota in germ-free animals because of the variation and dynamic state of infant microbial communities. In this study, the effects of age and strain on intestinal microbiota were observed in an infant human flora-associated (IHFA) mouse model. To establish an IHFA model, postnatal day (PND) 1 germ-free mice (Kunming, n = 10; BALB/c, n = 10) were infected with feces from a breast-fed infant. Microbiota in the feces of BALB/c mice (at PND 7, 14, and 21), and Kunming mice (at PND 14) were analyzed by PCR-denaturing gradient gel electrophoresis. Bifidobacteria and lactobacilli levels in the feces of BALB/c and Kunming mice (PND 7/14/21) were detected by quantitative real-time PCR. The Dice similarity coefficient (Cs) for the fecal microbiota of IHFA mice in comparison with the HD donor sample was higher for BALB/c mice than for Kunming mice (P < 0.05). In addition, the DCs at PND 7 were lower than those at PND 14 and PND 21 in both mouse strains (P < 0.05). The Bifidobacteria and Lactobacillus species colonizing the BALB/c mice were similar to those in the Kunming mice (at PND 7/14/21). The bifidobacteria counts increased with age in both mouse strains, whereas the lactobacilli counts decreased with age in both strains. These results suggest that both age and strain influence microbiota patterns in the IHFA mouse model.


T2 laryngeal carcinoma with impaired mobility: subtypes with therapeutic implications.
The aim of this study was to evaluate the outcome in the treatment of T2 laryngeal carcinoma with impaired laryngeal mobility, comparing surgical management to radiotherapy in terms of local control and survival. The files of 66 patients treated between 1988 and 1994 were retrospectively studied for tumor location, treatment and outcome. Forty-two patients were treated surgically and 24 by radiotherapy. Follow-up averaged 8.5 years. Local recurrence occurred in 12.5% of the cases treated by conservation laryngeal surgery and in 21% of the cases by radiotherapy. Ultimate laryngeal preservation was achieved in 90.9% of the cases initially treated by partial laryngectomy and in 87.5% of the cases treated by radiotherapy. Five-year actuarial survival rates were 90% and 28%, respectively. A higher rate of metastases and second primaries occurred in the group treated by radiotherapy. T2 laryngeal carcinoma amenable to partial laryngectomy had a higher local control rate than the cases not amenable to conservation surgery and treated by radiotherapy. Tumors differed in the two treatment groups in location and extensions, despite the fact that all were T2 tumors. We emphasize the limits of retrospective studies. Only prospective randomized studies will determine the true results of surgery versus radiotherapy for a homogeneous subset of T2 laryngeal tumors.


Similarity classifier with generalized mean applied to medical data.
A new approach based on fuzzy similarity was presented for the detection of erythemato-squamous diseases, diabetes, liver disorders, breast cancer and thyroid. The domain contained records of patients with known diagnoses. The results were very promising with all data sets and some conclusions can be drawn that a fuzzy similarity model can be used for the diagnosis of patients taking into consideration the error rate. A fuzzy similarity classifier was used to detect the six erythemato-squamous diseases when 34 features defining six disease indications were used as inputs. The results confirmed that the proposed model has potential in detecting erythemato-squamous diseases. The fuzzy similarity model achieved accuracy rates (over 97%) which were higher than that of the stand-alone neural network model or the ANFIS model suggested in [E.D. Ubeyli, I. Güler, Comput. Biol. Med. 35(5) (2005) 421-433]. With PIMA Indian diabetes, the detection model has an error rate of about 25% which is much better than the overall rate of 33% for diabetes. The model was also tested with other data sets: thyroid and two breast cancer data sets where the average detection accuracy was over 96% for all cases, which is quite good. Also, the liver disorder data set gave promising results.


Comparability of Cartesian Diver, Gilson, Warburg and Winkler methods of measuring the respiratory rates of aquatic invertebrates in ecological studies.
Comparison of Cartesian Diver-Winkler measurements of respiratory rates in larvae of the damselfly Pyrrhosoma nymphula, and Cartesian Diver-Gilson comparisons in the snail Potamopyrgus jenkinsi are descibed. Measurements of oxygen uptake using these different methods do not differ significantly for the same species of animal at the same temperature. Published data likewise suggest that Warburg and Winkler measurements can give similar results.All these methods, therefore, appear to be equally suitable for ecological work, providing they are used carefully and with a sound knowledge of the biology of the animal under investigation.


Patient with hypofibrinolysis-mediated thromboembolism converted to a hypercoagulable/hyperfibrinolytic state via ventricular assist device placement.
Mechanical circulatory support with ventricular assist devices (VADs) for end-stage heart failure has been a focus of intense interest for nearly four decades. Despite improvements in VAD design and biomaterial composition, it is common to administer anti-coagulation (e.g., warfarin, anti-platelet agents) to prevent both device thrombosis and thromboembolism. We present a patient with pre-operative thrombophilia (pulmonary embolism, intracardiac thrombus) and hypofibrinolysis, who subsequently developed hypercoagulability with hyperfibrinolysis with normalization of clot lifespan after left VAD placement. Such complex patient-VAD-hemostatic-state interactions serve as the rationale for continuing investigation of the effects of mechanical circulation on the fibrinolytic system and thrombophilia.


Two one-dimensional d¹⁰-metal coordination polymers based on polydentate Schiff-base ligand: synthesis, crystal structure and luminescent properties.
Two one-dimensional d(10)-metal coordination polymers {[AgL(H(2)O)](2)[AgL(NO(3))](2)(NO(3))(2)L(H(2)O)(2)}(n) (1) and [ZnLCl(2)](n) (2) (L=N,N'-bis-(1-pyridin-4-yl-ethylidene)-hydrazine) have been synthesized and characterized by IR, elemental analysis, TG technique, XRPD and X-ray crystallography. Polymer 1 contains two types of 1D Ag-double-chain units. Ag(1)-double-chain unit is formed by linking two adjacent Ag(1)-L-chains through face-to-face π⋯π interactions, while Ag(2)-double-chain unit is formed through the combination of coordinating NO(3)(-) anions bridging interactions and π⋯π interactions between two adjacent Ag(2)-L-chains. Free ligands interact with the adjacent Ag(1)-double-chain units and Ag(2)-double-chain units to form a 3D supramolecular structure through multiform hydrogen bonds. For polymer 2, each ligand acts as a bis-monodentate bridging ligand to bind adjacent Zn(II) centers forming a one-dimensional chain structure. Furthermore, 1D chain is held together with its neighboring ones via CH⋯π interactions. The luminescent properties of the polymers 1 and 2 were investigated in the solid state at room temperature.


Responses of transcriptome and metabolome in the roots of Pugionium cornutum (L.) Gaertn to exogenously applied phthalic acid.
The yield and quality of Pugionium cornutum (L.) Gaertn., a healthy, green vegetable with low sugar and high protein contents and high medicinal value, is severely affected by autotoxicity, which is a leading factor in the formation of plant disease. To help characterize the autotoxicity mechanism of P. cornutum (L.) Gaertn., we performed transcriptomic and metabolic analysis of the roots of P. cornutum (L.) Gaertn. response to phthalic acid, an autotoxin from P. cornutum (L.) Gaertn. In this study, high-throughput sequencing of nine RNA-seq libraries generated from the roots.of P. cornutum (L.) Gaertn. under different phthalic acid treatments yielded 37,737 unigenes. In total, 1085 (703 upregulated and 382 downregulated) and 5998 (4385 upregulated and 1613 downregulated) DEGs were identified under 0.1 and 10 mmol·L- 1 phthalic acid treatment, respectively, compared with the control treatment. Glutathione metabolism was among the top five important enriched pathways. In total, 457 and 435 differentially accumulated metabolites were detected under 0.1 and 10 mmol·L- 1 phthalic acid treatment compared with the control, respectively, of which 223 and 253, respectively, increased in abundance. With the increase in phthalic acid concentration, the accumulation of ten metabolites increased significantly, while that of four metabolites decreased significantly, and phthalic acid, dambonitol, 4-hydroxy-butyric acid, homocitrulline, and ethyl β-D-glucopyranoside were 100 times more abundant under the 10 mmol·L- 1 phthalic acid treatment than under the control. Seventeen differentially expressed genes significantly associated with phthalic acid content were identified. In addition, the L-histidinol content was highest under 0.1 mmol·L- 1 phthalic acid, and a total of eleven differentially expressed genes were significantly positively correlated with the L-histidinol content, all of which were annotated to heat shock proteins, aquaporins and cysteine proteases. Accumulation of autotoxins altered the metabolic balance in P. cornutum (L.) Gaertn. and influenced water absorption and carbon and nitrogen metabolism. These important results provide insights into the formation mechanisms of autotoxicity and for the subsequent development of new control measures to improve the production and quality of replanted plants.


Assessment of popliteal neurovascular safety during all-inside suturing of the posterior horn of the lateral meniscus using Upright MRIs of the knee joint.
To examine the risk of injury to the popliteal neurovascular bundle (pNVB) during all-inside repair of the posterior horn of the lateral meniscus (PHLM) using Upright-MRIs. Upright-MRIs of 61 knees in extension (ext) and 90°-flexion (flex) were included. Distance D from the PHLM to the pNVB was compared between extended and 90°-flexed position, subgroups with/without joint-effusion and evaluated according to demographics. Portal safety was assessed simulating suturing of the PHLM via four arthroscopy portals. Distance d (shortest space from the simulated suturing-device trajectory lines to the pNVB) was compared among portals in increasing distances from the posterior cruciate ligament (PCL). D is longer in flex (17.3 ± 6.0 mm) than in ext (11.3 ± 4.2 mm, p < 0.0001). MRIs with joint-effusion displayed longer values of D than scans without joint-effusion (flex: 20.4 ± 7.1 mm vs. 16.1 ± 5.2 mm, p = 0.012). Shorter distances are associated with female gender, lower body weight and lower BMI. At 0 mm from the PCL, the 1 cm-lateral portal was the safest (p < 0.0001) whereas at 3 mm/6mm/9mm/12 mm the 1 cm-medial portal showed the longest d values (p < 0.0001 each). All-inside suturing of the PHLM is safer in 90°-flexion, in presence of intraarticular fluid and in male patients with increasing weight/BMI. Sutures of the PHLM at 0 mm from the PCL are safer from a 1 cm-lateral portal whereas for tears located ≥ 3 mm from the PCL a 1 cm-medial portal involves a lower neurovascular risk. Upright-MRI proves excellent for preoperative planning to minimize neurovascular risks.


Perinatal outcome of monochorionic twin pregnancy complicated by selective fetal growth restriction according to management: systematic review and meta-analysis.
To explore the impact of severity and management (expectant, laser treatment or selective reduction) on perinatal outcome of monochorionic twin pregnancies complicated by selective fetal growth restriction (sFGR). MEDLINE, EMBASE, CINAHL, ClinicalTrials.gov and The Cochrane Library databases were searched for studies on outcome following expectant management, laser treatment or selective reduction in monochorionic twin pregnancies complicated by sFGR. Only pregnancies affected by sFGR and categorized according to the Gratacós classification (Type I, II or III) were included. The primary outcome was mortality, including single and double intrauterine (IUD), neonatal (NND) and perinatal deaths. Secondary outcomes were neonatal morbidity, abnormal postnatal brain imaging, intraventricular hemorrhage, periventricular leukomalacia, respiratory distress syndrome, admission to neonatal intensive care unit and survival free from neurological complications (intact survival). Meta-analyses of proportions were used to analyze the extracted data according to management, severity of sFGR and fetal size (smaller vs larger twin). Sixteen observational studies (786 monochorionic twin pregnancies) were included. In pregnancies complicated by Type-I sFGR managed expectantly, IUD occurred in 3.1% (95% CI, 1.1-5.9%) of fetuses and 97.9% (95% CI, 93.6-99.9%) of twins had intact survival. In pregnancies complicated by Type-I sFGR treated using laser therapy, IUD occurred in 16.7% (95% CI, 0.4-64.1%) of fetuses and, in those treated using selective reduction, IUD occurred in 0% (95% CI, 0-34.9%) of cotwins, with no evidence of neurological complications in the survivors. In pregnancies complicated by Type-II sFGR managed expectantly, IUD occurred in 16.6% (95% CI, 6.9-29.5%) and NND in 6.4% (95% CI, 0.2-28.2%) of fetuses, and 89.3% (95% CI, 71.8-97.7%) of twins survived without neurological compromise. In Type-II sFGR pregnancies treated using laser therapy, IUD occurred in 44.3% (95% CI, 22.2-67.7%) of fetuses, while none of the affected cases experienced morbidity and survivors were free of neurological complications. Of pregnancies undergoing selective reduction, IUD of the cotwin occurred in 5.0% (95% CI, 0.03-20.5%) and NND in 3.7% (95% CI, 0.2-11.1%), and 90.6% (95% CI, 42.3-94.3%) of surviving cotwins were free from neurological complications. In pregnancies complicated by Type-III sFGR managed expectantly, IUD occurred in 13.2% (95% CI, 7.2-20.5%) and NND in 6.8% (95% CI, 0.7-18.6%) of fetuses, and 61.9% (95% CI, 38.4-81.9%) of twins had intact survival. In pregnancies complicated by Type-III sFGR treated with laser therapy, IUD occurred in 32.9% (95% CI, 20.9-46.2%) of fetuses and all surviving twins were without neurological complications. Finally, in pregnancies with Type-III sFGR treated with selective reduction, NND occurred in 5.2% (95% CI, 0.8-12.8%) of cotwins and 98.8% (95% CI, 93.9-99.9%) had intact survival. Type-I sFGR is characterized by good perinatal outcome when managed expectantly, which represents the most reasonable management strategy for the large majority of affected cases. Pregnancies complicated by Type-II or -III sFGR treated with fetoscopic laser ablation have a higher rate of mortality but lower rate of morbidity compared with those managed expectantly, supporting the use of fetal therapy at gestations remote from neonatal viability. Data on outcome following selective reduction are scarce. In view of the lack of evidence from randomized controlled trials, prenatal management of sFGR should be individualized according to gestational age at diagnosis, severity of growth discordance and magnitude of Doppler anomalies. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.


Aurora kinase B is an independent protective factor in superficial bladder tumours with a dysfunctional G1 checkpoint.
To investigate the clinical role of Aurora kinases (essential for regulating mitosis) in human bladder pathogenesis, by quantifying Aurora kinase A and B, phospho-Aurora A, and phospho-Rb and p53 in bladder tumours, analysing the correlations between expression and clinicopathological features. We evaluated levels of Aurora A, B, phospho-Aurora A, phospho-Rb and p53 in 73 superficial bladder tumours using tissue microarrays and immunohistochemistry, and correlated expression with pathological variables and clinical outcome. None of the Aurora proteins, when analysed alone, significantly predicted either tumour recurrence or progression. In tumours with an aberrant G1 checkpoint, assessed by phospho-Rb and p53 status, expression of neither Aurora A nor its phosphorylated form predicted either tumour recurrence or progression. Surprisingly, high expression of Aurora B in tumours with an aberrant G1 checkpoint significantly protected from tumour recurrence. On multivariate analysis, Aurora B was the only significant factor that predicted tumour recurrence in the presence of either phospho-Rb or mutated p53. This difference was not evident in tumours with an intact G1 checkpoint. High expression of Aurora B in superficial bladder tumours with an aberrant G1 checkpoint significantly protects patients from tumour recurrence. The potential application of nonspecific Aurora kinase inhibitors in non-muscle-invasive bladder cancer might be detrimental.


The influence of soyfibre supplemented tube feeding on the occurrence of diarrhoea in postoperative patients.
We investigated the occurrence of diarrhoea in postoperative patients on tube feeding, with or without soyfibre supplementation. The patients also received antibiotic treatment. 60 postoperative patients were assigned to either a fibre free formula diet (FFF) or a soyfibre supplemented formula diet (SSF). The tube feeding was supplied continuously through a nasogastric or a jejunal tube (mean volume 1775 ml a day). The consistency and frequency of the bowel evacuations were recorded for a period of 5 days. A daily diarrhoea score (DS) was obtained by adding a consistency score (formed stools 1, loose 3, and watery 5 points) for every evacuation. The major finding of this study is that the total DS of the FFF group was 1.7 times higher than the SSF group (ANOVA, p = 0.05). We conclude that soyfibre enriched tube feeding has a beneficial and significant influence on the occurrence of diarrhoea in a selected group of postoperative patients.


Benign fibrous histiocytoma of the renal capsule.
The first case of benign fibrous histiocytoma of the renal capsule is reported in a male aged 44 years. The tumor had its point of origin in the renal capsule. Histologically, the tumor was composed of intersecting fascicles of fibroblastic cells forming a loose crisscross or "storiform" pattern. Electron microscopic studies of tumor cells revealed intermediate filaments and membrane-bound collagen fibers which continued to extracellular collagen bundles. This deep seated fibrous histiocytoma had a more prominent storiform pattern and fewer secondary elements such as xanthoma cells than cutaneous ones.


Morphea-like complications to illicit gluteal silicone injections.
We present a case of a 39-year-old Hispanic woman who was referred to our clinic for treatment of several indurated plaques on her buttocks that developed one year prior to presentation, after she received injections of an unknown substance for augmentation. Biopsy of one nodule revealed silicone in the dermis.


Deficiency of miR-409-3p improves myocardial neovascularization and function through modulation of DNAJB9/p38 MAPK signaling.
Angiogenesis is critical for tissue repair following myocardial infarction (MI), which is exacerbated under insulin resistance or diabetes. MicroRNAs are regulators of angiogenesis. We examined the metabolic regulation of miR-409-3p in post-infarct angiogenesis. miR-409-3p was increased in patients with acute coronary syndrome (ACS) and in a mouse model of acute MI. In endothelial cells (ECs), miR-409-3p was induced by palmitate, while vascular endothelial growth factor (VEGF) and fibroblast growth factor (FGF) decreased its expression. Overexpression of miR-409-3p decreased EC proliferation and migration in the presence of palmitate, whereas inhibition had the opposite effects. RNA sequencing (RNA-seq) profiling in ECs identified DNAJ homolog subfamily B member 9 (DNAJB9) as a target of miR-409-3p. Overexpression of miR-409-3p decreased DNAJB9 mRNA and protein expression by 47% and 31% respectively, while enriching DNAJB9 mRNA by 1.9-fold after Argonaute2 microribonucleoprotein immunoprecipitation. These effects were mediated through p38 mitogen-activated protein kinase (MAPK). Ischemia-reperfusion (I/R) injury in EC-specific miR-409-3p knockout (KO) mice (miR-409ECKO) fed a high-fat, high-sucrose diet increased isolectin B4 (53.3%), CD31 (56%), and DNAJB9 (41.5%). The left ventricular ejection fraction (EF) was improved by 28%, and the infarct area was decreased by 33.8% in miR-409ECKO compared with control mice. These findings support an important role of miR-409-3p in the angiogenic EC response to myocardial ischemia.


[Comparison of the efficiency of inhalation and injection anaesthesia for the castration of male suckling piglets in different organic farms].
In Germany, injection and inhalation anesthesia with the addition of an analgesic drug are an interim solution to surgical castration under general anesthesia due to the ban on non-anesthetic castration of male suckling piglets under 8 days of age. However, the efficiency of both anesthetic procedures is submit to controversial discussion. Most of the studies addressing this question only examined one of the procedures in comparison to piglets castrated without anesthesia or uncastrated controls. Comparisons between the anesthesia methods, especially under conditions of organically working farms, are almost completely lacking. The aim of the present study was therefore to compare the efficacy of injection and inhalation anesthesia under practical conditions in 7 organic farms as well as to examine the effect of metamizole administered in addition to meloxicam. For this purpose, 514 male suckling piglets were examined with regard to anesthesia efficiency (reflex test, defence behaviour), body temperature, post-operative bleeding and wound healing, post-operative behavior and pain behavior as well as the course of the recovery phase. The results show a basic superiority of inhalation anesthesia over injection anesthesia, especially in the areas of anesthetic efficacy, thermoregulation and duration of the recovery phase. In 7.7 to 15 % of piglets, the perianal and interclaw reflexes studied were still present at the time of castration. Following injection and inhalation anesthesia, in total 83.6 (25.2 %) of the piglets showed at least one of the following criteria: positive reflex response, clear defensive movements or vocalisations. Body temperature dropped by 0.41 °C under inhalation anesthesia and by 1.82 °C under injection anesthesia. Post-castration bleeding and wound healing were hardly influenced by the type of anesthesia. Almost all piglets showed signs of pain and pain-associated behavior for 5 and 72 hours after castration, regardless of the type of anesthesia. The post-castration recovery phases lasted significantly longer after injection anesthesia (107 minutes) than following inhalation anesthesia (33.3 minutes) until the piglets were returned to the sow. Neither injection nor inhalation anesthesia in spite of additional administration of meloxicam, nor the supplementary use of metamizole, fulfil the EU requirements for painless castration. The necessary analgesia during and after castration of male suckling piglets is not achieved under either isoflurane or ketamine/azaperone anesthesia, despite the use of meloxicam and metamizole.


Positive and negative brain zones in the snail.
Fine wire electrodes were surgically implanted in two regions of the brain of the snail Helix aspersa. To receive electrical stimulation of the brain, a tethered snail was required to displace the end of a rod. Self-stimulation delivered to the parietal ganglion resulted in non-repetition of the operant response, whereas self-stimulation delivered to the mesocerebrum resulted in an increase in response frequency. The reinforcing effect of local extracellular stimulation of two brain zones was investigated in a semi-intact preparation of a closely related species with an identical cellular map (H. lucorum). It was found that mesocerebral stimulation increased the frequency of the reinforced spontaneous movement, but decreased the frequency of the same movement if its absence was reinforced. These results allow us to attribute positive reinforcing effects to this brain area, which is involved in the control of sexual behaviour. Different results were obtained by contingent stimulation of the rostral part of the parietal ganglia, where giant cells controlling avoidance behaviour are located. Stimulation of this zone resulted in a decrease in the frequency of the ongoing spontaneous movements. These findings make possible intracellular investigations of the mechanisms of positive and negative reinforcement.


Foamy Monocytes Are Enriched in cis-7-Hexadecenoic Fatty Acid (16:1n-9), a Possible Biomarker for Early Detection of Cardiovascular Disease.
Human monocytes respond to arachidonic acid, a secretory product of endothelial cells, by activating the de novo pathway of fatty acid biosynthesis, resulting in the acquisition of a foamy phenotype due to accumulation of cytoplasmic lipid droplets. Recruitment of foamy monocytes to endothelium is a key step in the formation of atherosclerotic plaques. Here we describe that lipid droplets of foamy monocytes are enriched in a rather uncommon fatty acid, cis-7-hexadecenoic acid (16:1n-9), a positional isomer of palmitoleic acid. 16:1n-9 was found to possess an anti-inflammatory activity both in vitro and in vivo that is comparable with that of omega-3 fatty acids and clearly distinguishable from the effects of palmitoleic acid. Selective accumulation in neutral lipids of phagocytic cells of an uncommon fatty acid reveals an early phenotypic change that may provide a biomarker of proatherogenicity, and a potential target for intervention in the early stages of cardiovascular disease.


P2Y1R is involved in visceral hypersensitivity in rats with experimental irritable bowel syndrome.
To evaluate the role of P2Y1R in visceral hypersensitivity in rats with experimental irritable bowel syndrome. A rat model of irritable bowel syndrome was generated by intra-colonic administration of acetic acid (AA) and assessed by histology and myeloperoxidase (MPO) activity assay. Then P2Y1R expression in the colonic tissue was detected by Western blot. In order to explore the regulatory role of P2Y1R in visceral hypersensitivity, an agonist (MRS2365) and an antagonist (MRS2179) of P2Y1R were intra-colonically administered and effects were tested through a colorectal distension test. The abdominal withdrawal reflex and abdominal electromyography were tested during the course. Model assessment tests showed an obvious inflammatory reaction that appeared on the 2nd d after the AA injection, and the inflammatory reaction gradually recovered and almost disappeared on the 7th d. The model finished on day 8 and showed a clear feature of IBS that had no organic lesion. The average expression of P2Y1R was significantly higher in the AA group than in the naïve group (0.319 ± 0.02 vs 0.094 ± 0.016, P < 0.001). MRS2365 could effectively raise the colonic hypersensitivity status at intervention doses of 10 (AUC value from 0.30 ± 0.089 to 1.973 ± 0.127 mv·s, P < 0.01) and 100 μmol/L (AUC value from 0.290 ± 0.079 to 1.983 ± 0.195 mv·s, P < 0.01); MRS2179 could effectively reduce the hypersensitivity status at intervention dose of 100 μmol/L (from a mean baseline AUC value of 1.587 ± 0.099 mv·s to 0.140 ± 0.089 mv·s, P < 0.0001). Differences between the MRS2179 group (1.88 ± 1.45) and either the MRS2365 group (3.96 ± 0.19) or the combined treatment (MRS2179 and MRS2365) group (3.28 ± 0.11) were significant (P < 0.01). P2Y1R plays a regulatory role in visceral hypersensitivity in rats with experimental IBS. Specific antagonists of P2Y1R may have potential therapeutic value in treating abdominal pain in IBS.


The elderly population are more vulnerable for the management of colorectal cancer during the COVID-19 pandemic: a nationwide, population-based study.
The impact of coronavirus disease 2019 (COVID-19) on the management of colorectal cancer (CRC) may worse in elderly population, as almost all COVID-19 deaths occurred in the elderly patients. This study aimed to evaluate the impact of COVID-19 on CRC management in the elderly population. The numbers of patients who underwent colonoscopy, who visited hospitals or operated for CRC in 2020 and 2021 (COVID-19 era) were compared with those in 2019, according to 3 age groups (≥70 years, 50-69 years, and ≤49 years), based on the nationwide, population-based database (2019-2021) in South Korea. The annual volumes of colonoscopy and hospital visits for CRC in 2020 were more significantly declined in the old age group than in the young age group (both P<0.001). In addition, the annual volume of patients operated for CRC numerically more declined in old age group than in young age group. During the first surge of COVID-19 (March and April 2020), old age patients showed statistically significant declines for the monthly number of colonoscopies (-46.5% vs. -39.3%, P<0.001), hospital visits (-15.4% vs. -7.9%, P<0.001), CRC operations (-33.8% vs. -0.7%, P<0.05), and colonoscopic polypectomies (-41.8% vs. -38.0%, P<0.001) than young age patients, compared with those of same months in 2019. Elderly population are more vulnerable for the management of CRC during the COVID-19 pandemic. Therefore, the elderly population are more carefully cared for in the management of CRC during the next pandemic.


Autoantibody diversity in paraneoplastic syndromes and related disorders: The need for a more guided screening approach.
Significant progress has been made in understanding the role and diversity of autoantibodies in the pathogenesis, diagnosis and management of paraneoplastic syndrome (PNS) and related autoimmune neurologic diseases. We evaluated the positivity rates for diverse autoantibody panels to rationalize testing strategies and utilization. The result patterns for different autoantibody panels for PNS offered at 2 reference laboratories in the U.S. were retrospectively reviewed for the same period. The positivity rates were evaluated and compared for specific autoantibodies within panels offered at both laboratories. For the Hu, Ri, Yo, and amphiphysin antibodies offered by both laboratories, no significant difference in positivity rates was observed. The positivity rates for non-classic PNS markers were 0% [AGNA and PCCA-Tr], and 0.06% [ANNA-3 and PCAC-2] while the prevalence of antibodies associated with neuromuscular autoimmunity varied from 1.40% to 4.44% [Striated muscle, AChR binding, ganglionic AChR, VGCC, P/Q- and N-type VGCC]. The data suggest that test utilization could be substantially improved based on ordering practice geared towards clinical manifestations and prevalence of autoantibodies. Concerted efforts towards streamlining diagnostic algorithms based on risk, clinical manifestations, characterization of autoantibodies and their associations as well as therapeutic strategies are needed.


Monolayered Bi2WO6 nanosheets mimicking heterojunction interface with open surfaces for photocatalysis.
Two-dimensional-layered heterojunctions have attracted extensive interest recently due to their exciting behaviours in electronic/optoelectronic devices as well as solar energy conversion systems. However, layered heterojunction materials, especially those made by stacking different monolayers together by strong chemical bonds rather than by weak van der Waal interactions, are still challenging to fabricate. Here the monolayer Bi2WO6 with a sandwich substructure of [BiO](+)-[WO4](2-)-[BiO](+) is reported. This material may be characterized as a layered heterojunction with different monolayer oxides held together by chemical bonds. Coordinatively unsaturated Bi atoms are present as active sites on the surface. On irradiation, holes are generated directly on the active surface layer and electrons in the middle layer, which leads to the outstanding performances of the monolayer material in solar energy conversion. Our work provides a general bottom-up route for designing and preparing novel monolayer materials with ultrafast charge separation and active surface.


Ligand based virtual screening using SVM on GPU.
In silico methods play an essential role in modern drug discovery methods. Virtual screening, an in silico method, is used to filter out the chemical space on which actual wet lab experiments are need to be conducted. Ligand based virtual screening is a computational strategy using which one can build a model of the target protein based on the knowledge of the ligands that bind successfully to the target. This model is then used to predict if the new molecule is likely to bind to the target. Support vector machine, a supervised learning algorithm used for classification, can be utilized for virtual screening the ligand data. When used for virtual screening purpose, SVM could produce interesting results. But since we have a huge ligand data, the time taken for training the SVM model is quite high compared to other learning algorithms. By parallelizing these algorithms on multi-core processors, one can easily expedite these discoveries. In this paper, a GPU based ligand based virtual screening tool (GpuSVMScreen) which uses SVM have been proposed and bench-marked. This data parallel virtual screening tool provides high throughput by running in short time. The proposed GpuSVMScreen can successfully screen large number of molecules (billions) also. The source code of this tool is available at http://ccc.nitc.ac.in/project/GPUSVMSCREEN.


Patients with minimal hepatic encephalopathy have poor insight into their driving skills.
Minimal hepatic encephalopathy (MHE) is associated with impaired driving skills. It is not clear whether patients have insight into this. The Driving Behavior Survey (DBS) is a validated self- or observer-administered questionnaire. DBS consists of a total score (maximum, 104) and an attention-related driving skills section (maximum, 40). DBS was used to compare self-assessment with observer-assessment of driving skills in cirrhotic patients tested for MHE. Forty-seven nonalcoholic cirrhotic patients and 40 controls underwent psychometric tests, DBS, and driving simulation with navigation/driving tasks. An adult familiar with the subject's driving completed the DBS independently. Simulator performances, total DBS scores, and driving skill scores were compared between/within groups (MHE+, MHE-, and controls) with respect to self-assessment and observer assessment. Thirty-six patients were MHE+ and 11 were MHE-. MHE+ had a significantly higher simulator crash (MHE+, 3; MHE-, 1.2; controls, 1.7; P = .001) and illegal turn rate (MHE+, 1.2; MHE-, 0.3; controls, 0.1; P = .0001). Despite this worse performance, MHE+ patients rated themselves similar to MHE- patients and control groups on total (P = .28) and driving skills scores (P = .19). Observer assessment in MHE+ was significantly lower for total (P = .0001) and driving skills (P = .0001) compared with observer assessment for MHE- patients and control groups. MHE+ patients were rated significantly lower on driving skills (34 vs 37; P = .02) and trended lower in the total score (P = .08) by observers compared with self-ratings. In contrast, MHE- and control groups rated themselves similar to their observers on driving skills and total DBS scores. MHE patients have poor insight into their driving skills. A part of the MHE patient's clinical interview should be to increase awareness of this driving impairment.


Bcl-2 family regulation of neuronal development and neurodegeneration.
Neuronal cell death is a key feature of both normal nervous system development and neuropathological conditions. The Bcl-2 family, via its regulation of both caspase-dependent and caspase-independent cell death pathways, is uniquely positioned to critically control neuronal cell survival. Targeted gene disruptions of specific bcl-2 family members and the generation of transgenic mice overexpressing anti- or pro-apoptotic Bcl-2 family members have confirmed the importance of the Bcl-2 family in the nervous system. Data from studies of human brain tissue and experimental animal models of neuropathological conditions support the hypothesis that the Bcl-2 family regulates cell death in the mature nervous system and suggest that pharmacological manipulation of Bcl-2 family action could prove beneficial in the treatment of human neurological conditions such as stroke and neurodegenerative diseases.


Surface charge response of the phosphatidylcholine head group in bilayered micelles from phosphorus and deuterium nuclear magnetic resonance.
Solid-state phosphorus (31P) and deuterium (2H) nuclear magnetic resonance (NMR) spectroscopy over the temperature range of 25-50 degreesC were used to investigate bilayered micelles (bicelles) composed of 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) and 1, 2-dihexanoyl-sn-glycero-3-phosphocholine (DHPC) in the presence of either the anionic lipid 1,2-dimyristoyl-sn-3-phosphoglycerol (DMPG) or the cationic lipid 1,2-dimyristoyl-3-trimethylammonium-propane (DMTAP). The 31P-NMR spectra demonstrate that bicellar structures form with DMPG/DMPC ratios ranging from 0 to 50/50 and with DMTAP/DMPC ratios from 0 to 40/60, while the overall concentration of DHPC remains constant. The formation of bicelles containing charged amphiphiles is contingent upon the presence of NaCl, with 50 mM NaCl being sufficient for bicelle formation at all concentrations of charged amphiphile investigated, while 150 mM NaCl affords better resolution of the various 31P-NMR resonance signals. The 2H-NMR spectra demonstrate that the quadrupolar splittings (Deltanu) of head group-deuterated DMPC change inversely as a function of the amount of negative versus positive charge present, and that the changes for deuterons on the alpha-carbon are opposite in sense to those for deuterons on the beta-carbon. This indicates that head group-deuterated phosphatidylcholine functions as a molecular voltmeter in bicelles in much the same fashion as it does in spherical vesicles.


Platelet-rich plasma for periodontal regeneration in the treatment of intrabony defects: a meta-analysis on prospective clinical trials.
The aim of this systematic review and meta-analysis was to assess the influence of platelet-rich plasma (PRP) on the regeneration of periodontal intrabony defects by means of evaluating clinical and radiographic outcomes in prospective human clinical trials. PRP is a high concentration of platelets suspended in a small volume of plasma and has been used for periodontal tissue regeneration. However, although it has been broadly studied, there is much controversy on its efficacy when used to treat infrabony periodontal defects. An electronic literature search was conducted by two reviewers (AR and AM) in several databases up to February 2014. The PICO question was: Does PRP have a higher or similar efficacy of regenerating periodontal intrabony defects compared with other conventional periodontal regeneration treatments (e.g., bone grafts, barrier membranes)? Articles were included in this systematic review if they were prospective clinical trials with 10 or more human patients, reporting the radiographic and/or clinical outcomes PRP for regeneration intrabony periodontal defects. Random effects meta-analyses of the selected studies were applied to avoid any bias being caused by methodologic differences among studies. Twenty-two papers were obtained and reviewed. Of these, 21 articles fulfilled the inclusion criteria and subsequently were qualitatively analyzed. Eighteen of these could be meta-analyzed. Fourteen articles were included for evaluating of probing pocket depth (PPD). The weighted mean difference (WMD) was 0.55 mm, with a 95% CI=-0.09 to 1.20 mm (P=.09). For bone level (BL), 2 articles measured BL in millimeters, and the other two articles measured BL in percentage. The WMD was 0.76 mm (95% CI=0.21-1.31 mm; P=.007) and 47.41% (95% CI=32.48%-62.33%; P<.0001), respectively. For attachment level (AL) changes, 12 articles were included. The WMD was 0.58 mm, with a 95% CI=0.24 to 0.91 mm (P=.0008). Sixteen articles were included for evaluation of marginal gingival level (MGL). The WMD -0.10 mm, with a 95% CI=-0.19 to -0.01 (P=.03). High heterogeneity among studies made it difficult to draw clear conclusions. Nonetheless, within the limitations of this review, PRP might offer some beneficial effects on clinical and radiographic outcomes for regeneration of periodontal intrabony defects.


Randomized trial comparing cyclophosphamide, epirubicin, and fluorouracil with cyclophosphamide, methotrexate, and fluorouracil in premenopausal women with node-positive breast cancer: update of National Cancer Institute of Canada Clinical Trials Group Trial MA5.
Certain anthracycline-containing adjuvant chemotherapy regimens are associated with improved relapse-free survival (RFS) and overall survival (OS) compared with the classic regimen of cyclophosphamide, methotrexate, and fluorouracil in women with early-stage breast cancer. Between 1989 and 1993, 710 pre- and perimenopausal women with axillary node-positive breast cancer were randomly assigned to either cyclophosphamide 75 mg/m(2) orally days 1 through 14, epirubicin 60 mg/m(2) intravenously days 1 and 8, and fluorouracil 500 mg/m(2) intravenously days 1 and 8 (CEF) or CMF (cyclophosphamide 100 mg/m(2) orally days 1 through 14, methotrexate 40 mg/m(2) intravenously days 1 and 8, and fluorouracil 600 mg/m(2) intravenously days 1 and 8). On the basis of follow-up to May 1997 (median follow-up time, 59 months), there was a statistically significant improvement in RFS and OS for CEF compared with CMF. The trial results are now updated, with a median follow-up of 10 years for live patients. The 10-year RFS is 52% for patients who received CEF compared with 45% for CMF patients (hazard ratio [HR] for CMF v CEF = 1.31; stratified log-rank, P = .007). The 10-year OS for patients who received CEF and CMF are 62% and 58%, respectively (HR for CMF v CEF = 1.18; stratified log-rank, P = .085). The rates of acute leukemia have not changed since the original report, whereas the rates of congestive heart failure are slightly higher but acceptable (four patients [1.1%] in the CEF group v one patient [0.3%] in the CMF group). The previously demonstrated benefit of CEF compared with CMF adjuvant chemotherapy is maintained with longer follow-up in the MA5 trial.


So, Doctor, Now, What Do I Do?
This paper proposes a discussion about acting on the therapeutic relationship using the notions of playing and the "use of an object" formulated by Winnicott; the formulations of Ferenczi as the concepts of introjection and the "ability to feel with", as well as the concept of cartography from Deleuze and Guattari. It discusses how to manage the meeting with individuals who confront the analyst with sudden questions, gestures and actions. I propose that the management of the acting considers that there is a call for a conversation in which "doing" is in question, and in which the playful dimension of activities without rules is employed as a necessary option.


Acute response to cholinergic challenge predicts long-term response to galantamine treatment in patients with Alzheimer's disease.
Cholinesterase inhibitors (CEIs) have been shown to improve cognitive functioning in Alzheimer's disease (AD) patients, but are associated with multiple side effects and only 20-40% of the patients clinically improve. In this study, we aimed to investigate the acute pharmacodynamic (PD) effects of administration of a single dose of galantamine on central nervous system (CNS) functioning in mild to moderate AD patients and its potential to predict long-term treatment response. This study consisted of a challenge and treatment phase. In the challenge phase, a single dose of 16 mg galantamine was administered to 50 mild to moderate AD patients in a double-blind, placebo-controlled cross-over fashion. Acute PD effects were monitored up to 5 hours after administration with use of the NeuroCart CNS test battery and safety and pharmacokinetics were assessed. In the treatment phase, patients were treated with open-label galantamine according to regular clinical care. After 6 months of galantamine treatment, patients were categorized as either responder or as non-responder based on their minimental state examination (MMSE), neuropsychiatric inventory (NPI) and disability assessment in dementia (DAD) scores. An analysis of covariance was performed to study the difference in acute PD effects during the challenge phase between responders and non-responders. A single dose of galantamine significantly reduced saccadic reaction time (-0.0099; 95% CI = -0.0195, -0.0003; P = .0430), absolute frontal EEG parameters in alpha (-14.9; 95% CI = -21.0, -8.3; P = .0002), beta (-12.6; 95% CI = -19.4, -5.3; P = .0019) and theta (-17.9; 95% CI = -25.0, -10.0; P = .0001) frequencies. Relative frontal (-1.669; 95% CI = -2.999, -0.339; P = .0156) and occipital (-1.856; 95% CI = -3.339, -0.372; P = .0166) EEG power in theta frequency and relative occipital EEG power in the gamma frequency (1.316; 95% CI = 0.158, 2.475; P = .0273) also increased significantly compared to placebo. Acute decreases of absolute frontal alpha (-20.4; 95% CI = -31.6, -7.47; P = .0046), beta (-15.7; 95% CI = -28.3, -0.93; P = .0390) and theta (-25.9; 95% CI = -38.4, -10.9; P = .0024) EEG parameters and of relative frontal theta power (-3.27%; 95% CI = -5.96, -0.58; P = .0187) on EEG significantly distinguished responders (n = 11) from non-responders (n = 32) after 6 months. This study demonstrates that acute PD effects after single dose of galantamine are correlated with long-term treatment effects and that patients who demonstrate a reduction in EEG power in the alpha and theta frequency after a single administration of galantamine 16 mg will most likely respond to treatment.


First synthesis of beta-keto sulfoxides by a palladium-catalyzed carbonylative Suzuki reaction.
[reaction: see text] An unprecedented palladium-catalyzed three-component cross-coupling reaction between alpha-bromo sulfoxide, carbon monoxide, and aromatic boronic acids provides a new and efficient approach to the synthesis of beta-ketosulfoxides. The reaction takes place under mild conditions with a wide range of variously substituted aryl and heteroaryl boronic acids. The carbonylative cross-coupling reaction is strongly favored over competing direct cross-coupling and homocoupling processes, except with boronic acids carrying strong electron-withdrawing substituents.


Plasma norepinephrine and heart rate dynamics during recovery from submaximal exercise in man.
The time course of heart rate (HR) and venous blood norepinephrine concentration [NE], as an expression of the sympathetic nervous activity (SNA), was studied in six sedentary young men during recovery from three periods of cycle ergometer exercise at 21% +/- 2.8%, 43% +/- 2.1% and 65% +/- 2.3% of VO2max respectively (mean +/- SE). The HR decreased mono-exponentially with tau values of 13.6 +/- 1.6 s, 32.7 +/- 5.6 s and 55.8 +/- 8.1 s respectively in the three periods of exercise. At the low exercise level no change in [NE] was found. At medium and high exercise intensity: (a) [NE] increased significantly at the 5th min of exercise (delta [NE] = 207.7 +/- 22.5 pg.ml-1 and 521.3 +/- 58.3 pg.ml-1 respectively); (b) after a time lag of 1 min [NE] decreased exponentially (tau = 87 s and 101 s respectively); (c) in the 1st min HR decreased about 35 beats.min-1; (d) from the 2nd to 5th min of recovery HR and [NE] were linearly related (100 pg.ml-1 delta [NE] congruent to 5 beats.min-1). In the 1st min of recovery, independent of the exercise intensity, the adjustment of HR appears to have been due mainly to the prompt restoration of vagal tone. The further decrease in HR toward the resting value could then be attributed to the return of SNA to the pre-exercise level.


Synthesis of sequence-ordered polymers via sequential addition of monomers in one pot.
Sequence-ordered polymers can be simply prepared in one pot via sequential monomer addition.


A compound isolated from Schisandra chinensis induces apoptosis.
Schizandra chinensis has been known to have five predominant tastes: salty, sweet, sour, astringent, and bitter. It has also been shown to have various effects on the cardiovascular system, gastrointestinal system, anti-inflammatory, central nervous system, endocrine system, and stress protect. However, its anti-cancer activity on colon carcinoma HCT-116 cells has not been yet been examined. Thus, in this study, we attempted to isolate a compound from Schisandra chinensis that induced apoptosis in HCT-116 cells. An active compound was found and identified to be Gomisin A. It displayed apoptotic activity through caspase-7 cleavage in colon carcinoma HCT-116 cells. In addition, we further assessed the effects of this compound using long-term survival clonogenic assay with HCT116 cells.


[Relationship between alpha-ENaC gene Thr663Ala polymorphism and ischemic stroke].
To determine the relationship between Thr663Ala polymorphism in amiloride-sensitive epithelial sodium channel alpha-subunit (alpha-ENaC) gene and ischemic stroke in Chinese population. Two hundred and ninety-four patients with cerebral infarction and 280 controls without stroke were screened by polymerase chain reaction (PCR) and corresponding Thr663Ala polymorphism probe hybridization. Thr663Ala polymorphism was in agreement with Hardy-Weinberg equilibrium. Both the carriers proportion (70.75%) and the frequency (48.64%) of 663Ala allele in patients were more prevalent than that in controls (62.86% and 40.89%) (P < 0.05). The presence of at least one 663Ala allele conferred an odds ratio for stroke of 1.429 (95%CI: 1.009-2.025), and the proportion of attributable risk of population (PAR%) was 11.63%. Thr 663Ala polymorphism of alpha-ENaC gene may be a genetic risk of ischemic stroke in Chinese population.


PDGF receptors in tumor stroma: Biological effects and associations with prognosis and response to treatment.
Platelet-derived growth factor (PDGF) ligands and their receptors (PDGFRα and PDGFRβ) regulate mesenchymal cells, such as fibroblasts and pericytes. These cells are important constituents of tumor stroma where they impact on tumor growth, metastasis and drug response. Studies in model systems have demonstrated ability of the PDGF system to regulate the tumor-stimulatory effects of fibroblasts, as well as their ability to promote cancer cell migration and invasion. Animal studies imply PDGFR-signaling as a regulator of tumor drug uptake. Emerging correlative analyses of different tumor collections are identifying clinically relevant variations in stromal PDGFR status, and associations between PDGFR status in tumor stroma and survival. These associations could either relate to effects of stromal PDGFR signaling on the natural course of the disease or response to treatment. The availability of clinically approved PDGFR-inhibitory drugs suggest interesting possibilities for novel clinical studies, performed on selected patient sub-groups, which further exploits tumor stroma-derived PDGFR signaling.


Elimination of and heart rate response to atropine in the elderly are independent of sex.
Sex-related changes in the pharmacokinetics and pharmacodynamics (heart rate) of atropine were studied in female (n = 9) and male (n = 9) elderly patients after a single 0.02 mg/kg i.v. injection of the drug at the beginning of a combination anaesthesia. No significant differences were found between the sexes, which indicates that there are no sex-related alterations in the response to this anticholinergic agent.