Increased susceptibility of mitochondria isolated from frontal cortex and hippocampus of vitamin A-treated rats to non-aggregated amyloid-β peptides 1-40 and 1-42.
Vitamin A is a redox-active molecule and its inadvertent utilisation as a preventive therapy against ageing or neurodegeneration has become a harmful habit among humans at different ages. Mitochondrial dysfunction and redox impairment may be induced by vitamin A supplementation experimentally. Nonetheless, it is still not clear by which mechanisms vitamin A elicits such effects. Then, we performed this investigation to analyse whether mitochondria isolated from frontal cortex and hippocampus of vitamin A-treated rats are more sensitive to a challenge with amyloid-β (Aβ) peptides 1-40 or 1-42. Adult Wistar rats received vitamin A at 1000-9000 IU/kg/day orally for 28 days. Then, mitochondria were isolated and the challenge with Aβ peptides 1-40 or 1-42 (at 0.2 or 0.1 μM, respectively) for 10 min was carried out before mitochondrial electron transfer chain enzyme activity, superoxide anion radical (O2 -•) production and 3-nitrotyrosine content quantification. Mitochondria obtained from vitamin A-treated rats are more sensitive to Aβ peptides 1-40 or 1-42 than mitochondria isolated from the control group, as decreased mitochondrial complex enzyme activity and increased O2 -• production and 3-nitrotyrosine content were observed in incubated mitochondria isolated from vitamin A-treated rats. These data suggest that oral intake of vitamin A at clinical doses increases the susceptibility of mitochondria to a neurotoxic agent even at low concentrations.


Structural studies of the tethered N-terminus of the Alzheimer's disease amyloid-β peptide.
Alzheimer's disease is the most common form of dementia in humans and is related to the accumulation of the amyloid-β (Aβ) peptide and its interaction with metals (Cu, Fe, and Zn) in the brain. Crystallographic structural information about Aβ peptide deposits and the details of the metal-binding site is limited owing to the heterogeneous nature of aggregation states formed by the peptide. Here, we present a crystal structure of Aβ residues 1-16 fused to the N-terminus of the Escherichia coli immunity protein Im7, and stabilized with the fragment antigen binding fragment of the anti-Aβ N-terminal antibody WO2. The structure demonstrates that Aβ residues 10-16, which are not in complex with the antibody, adopt a mixture of local polyproline II-helix and turn type conformations, enhancing cooperativity between the two adjacent histidine residues His13 and His14. Furthermore, this relatively rigid region of Aβ (residues, 10-16) appear as an almost independent unit available for trapping metal ions and provides a rationale for the His13-metal-His14 coordination in the Aβ1-16 fragment implicated in Aβ metal binding. This novel structure, therefore, has the potential to provide a foundation for investigating the effect of metal ion binding to Aβ and illustrates a potential target for the development of future Alzheimer's disease therapeutics aimed at stabilizing the N-terminal monomer structure, in particular residues His13 and His14, and preventing Aβ metal-binding-induced neurotoxicity.


Ethiopian National Hepatitis B Study.
A nationwide seroepidemiological study of hepatitis B markers prevalence was conducted in Ethiopia on 5,270 young males from all regions of the country. Overall prevalence rates were 10.8% for HBsAg and 73.3% for "at least one marker positive"; a remarkable geographical and ethnic variability of marker prevalence was observed, reflecting the wide differences existing in Ethiopia in sociocultural environment and activities such as tribal practices and traditional surgery. Sexual practices and medical exposure also play some role as determinants of hepatitis B marker prevalence in Ethiopia. General preventive measures, with particular reference to health education, by affecting incriminating habits and practices could have some impact on infection rates in Ethiopia, in the absence of a vaccination strategy presently unrealistic in this region of the world.


Synthetic bile acid derivatives induce apoptosis through a c-Jun N-terminal kinase and NF-kappaB-dependent process in human cervical carcinoma cells.
Recently, we have reported that a synthetic derivative of ursodeoxycholic acid (UDCA), HS-1183, and those of chenodeoxycholic acid (CDCA), HS-1199 and HS-1200, induced apoptosis in human breast carcinoma cells through a p53-independent pathway. Here, we present that the synthetic bile acid derivatives induce apoptosis in SiHa human cervical carcinoma cells as well. The parental compounds, UDCA and CDCA, exhibited no significant effect on the cell viability at the concentration ranges tested. However, their synthetic bile acid derivatives significantly decreased cell viability in a concentration dependent manner. Characteristic manifestations of apoptosis including DNA fragmentation, an increased level of proapoptotic protein Bax, and cleavage of poly(ADP-ribose) polymerase were shown when the cells were treated with these synthetic compounds. Nuclear translocation of nuclear transcription factor NF-kappaB was increased and this suggests that the synthetic compounds induce apoptosis in a NF-kappaB dependent pathway. Phosphorylations of p38 and extracellular signal-regulated kinase were not affected, whereas c-Jun N-terminal kinase (JNK) was activated along with an increased level of transcription factor c-Jun. Our studies demonstrate that the newly synthesized bile acids are capable of inhibiting cell proliferation and inducing apoptosis in SiHa cells through activation of JNK and NF-kappaB.


Induction of 8-azaguanine- and ouabain-resistant mutants by cyclophosphamide and 1-(pyridyl-3)-3,3-dimethyltriazene in Chinese hamster cells cultured in diffusion chambers in mice.
A host-mediated assay is described for induction of 8-azaguanine-resistant (azgr) and ouabain-resistant (ouar) mutants in Chinese hamster V79 cells cultured in diffusion chambers (DC) in C3H mice. Injection of the hosts with the indirect mutagen/carcinogen cyclophosphamide (CPP) or 1-(pyridyl-3)-3,3-dimethyltriazene (PyDT) caused a dose-dependent increase in mutation frequency at the loci of azgr and ouar in the V79 target cells. Plating efficiency of V79 cells in DC in mice was decreased depending upon the dose of CPP or PyDT given to the hosts. In addition, the relationship between expression time and mutation frequency was examined and discussed. The data support the use of this system as an effective screening procedure for suspected environmental mutagens or carcinogens, especially those that need to be metabolically activated in vivo.


Recovery of injured adrenal medulla by differentiation of pre-existing undifferentiated chromaffin cells.
We described previous that the adrenal medulla recovers rapidly from the injuries due to salinomycin. In the present study we found the recovery to be apparently due to differentiation of pre-existing, primitive undifferentiated, chromaffin cells, rather than mitosis, as evidenced by lack of incorporation of 5-bromo-2-deoxyuridine in the differentiating and/or differentiated chromaffin cells. Electron-dense, striated fibrils observed within the necrotic cells and in the extracellular space were presumed to be intermediate degradation products. Schwann cells actively functioned as phagocytes in this study, and seemed to indirectly stimulate the differentiation of undifferentiated chromaffin cells.


The establishment of a clinical diagnostic method of the visual evoked potentials (VEPs) in the cat: the effects of recording electrode positions, stimulus intensity and the level of anesthesia.
The establishment of characteristic wave pattern of visual evoked potentials (VEPs) in the cat was attempted in order to be aid for clinical veterinary practitioners with the evaluation of visual dysfunction. 1) The position where the largest response of the VEPs was detected was close to the midline of the occipital area in normal cats. 2) The VEPs consisted of three components with latencies within 100 msec after flash stimulus. 3) Flash stimuli of higher illumination produced VEPs of shorter latencies and increased amplitude. Intensity of more than 0.6 J was necessary to obtain stable VEP patterns. 4) The latencies of VEPs hardly changed with time course under pentobarbital anesthesia, although they showed a fluctuant variation.


Bicyclist injury severity in traffic crashes: A spatial approach for geo-referenced crash data to uncover non-stationary correlates.
Bicyclists are among vulnerable road users with their safety a key concern. This study generates new knowledge about their safety by applying a spatial modeling approach to uncover non-stationary correlates of bicyclist injury severity in traffic crashes. The approach is Geographically Weighted Ordinal Logistic Regression (GWOLR), extended from the regular Ordered Logistic Regression (OLR) by incorporating the spatial perspective of traffic crashes. The GWOLR modeling approach allows the relationships between injury severity and its contributing factors to vary across the spatial domain, to account for the spatial heterogeneity. This approach makes use of geo-referenced data. This study explored more than 7,000 geo-referenced bicycle--motor-vehicle crashes in North Carolina. This study performed a series of non-stationarity tests to identify local relationships that vary substantially across the spatial domain. These local relationships are related to the bicyclist (bicyclist age, bicyclist behavior, bicyclist intoxication, bicycle direction, bicycle position), motorist (driver age, driver intoxication, driver behavior, vehicle speed, vehicle type) and traffic (traffic volume). Results from the regular OLR are in general consistent with previous findings. For example, an increased bicyclist injury severity is associated with older bicyclists, bicyclist being intoxicated, and higher motor-vehicle speeds. Results from the GWOLR show local (rather than global) relationships between contributing factors and bicyclist injury severity. Practical Applications: Researchers and practitioners may use GWOLR to prioritize cycling safety countermeasures for specific regions. For example, GWOLR modeling estimates in the study highlighted the west part (from Charlotte to Asheville) of North Carolina for increased bicyclist injury severity due to the intoxication of road users including both bicyclists and drivers. Therefore, if a countermeasure is concerned with the road user intoxication, there may be a priority for the region from Charlotte to Asheville (relative to other areas in North Carolina).


Exploring Shigella vaccine priorities and preferences: Results from a mixed-methods study in low- and middle-income settings.
Shigella is the leading bacterial cause of diarrheal mortality in children and can cause long-term effects on growth and development. No licensed Shigella vaccines currently exist but several promising candidates are in development and could be available in the next five years. Despite Shigella being a well-known public health target of the World Health Organization for decades, given current burden estimates and competing preventable disease priorities in low-income settings, whether the availability of an effective Shigella vaccine will lead to its prioritization and widespread introduction among countries at highest risk is unknown. We conducted a mixed-methods study of national stakeholders and healthcare providers in five countries in Asia and Africa and regional stakeholders in the Pan American Health Organization to identify preferences and priorities for forthcoming Shigella vaccines. In our study of 89 individuals, diarrhea was the most frequently mentioned serious health concern for children under five years. Antimicrobial resistance (AMR) was more often considered very concerning than diarrhea or stunting. Shigella awareness was high but not considered a serious health concern by most stakeholders. Most participants were willing to consider adding a new vaccine to the routine immunization schedule but expressed reservations about a Shigella vaccine because of lower perceived burden relative to other preventable diseases and an already crowded schedule; interest was highest among national stakeholders in countries receiving more financial support for immunization. The priority of a Shigella vaccine rose when participants considered vaccine impacts on reducing stunting and AMR. Participants strongly preferred oral and combination vaccines compared to injectable and a single-antigen presentations, citing greater perceived community acceptability. This study provides a critical opportunity to hear directly from country and regional stakeholders about health priorities and preferences around new vaccines. These findings should inform ongoing Shigella vaccine development efforts and eventual vaccine introduction and implementation planning.


The CIAO (Coronary Interventions Antiplatelet-based Only) Study: a randomized study comparing standard anticoagulation regimen to absence of anticoagulation for elective percutaneous coronary intervention.
We sought to evaluate, in a double-blind, randomized, prospective study, safety and efficacy of elective percutaneous coronary intervention (PCI), with pharmacotherapy consisting of antiplatelet therapy and no anticoagulation therapy. Available guidelines recommend systemic anticoagulation agent use during PCI. Significant debate remains, however, with regard to the correlation between the effects of systemic anticoagulation therapy and ensuing ischemic and hemorrhagic complications. From June 2005 to January 2007, 700 patients undergoing elective PCI of an uncomplicated lesion have been prospectively enrolled in the protocol. Patients should have been on aspirin and thienopyridine therapy and were assigned either to the control arm (70 to 100 UI/kg unfractionated heparin) or to the no-heparin arm. A clinical assessment was obtained before hospital discharge and at 30 days after PCI. Procedural success was obtained in 100% of the cases. No acute or subacute thrombosis was observed. The absence of anticoagulation therapy was associated with a significant decrease in post-procedural myocardial damage (p = 0.03) and bleeding events (p = 0.048). At 30 days, the primary end point (death, myocardial infarction, or urgent target vessel revascularization) was more frequent in the control arm than in the no-heparin arm (2.0% vs. 3.7%, respectively; absolute risk reduction 1.7% [95% confidence interval: -0.1% to 4.5%], p for superiority = 0.17, p for noninferiority <0.001). In the treatment of uncomplicated lesions and in the presence of dual antiplatelet therapy, elective PCI can be safely performed without systemic anticoagulation and is associated with a reduced incidence of bleeding complications.


Carbon nanomaterials in oncology: an expanding horizon.
Carbon nanomaterials have been attracting attention in oncology for the development of safe and effective cancer nanomedicines in increasing improved patient compliance for generally recognized as safe (GRAS) prominence. Toxicity, safety and efficacy of carbon nanomaterials are the major concerns in cancer theranostics. Various parameters such as particle size and shape or surface morphology, surface charge, composition, oxidation and nonoxidative-stress-related mechanisms are prone to toxicity of the carbon nanomaterials. Currently, few cancer-related products have been available on the market, although some are underway in preclinical and clinical phases. Thus, our main aim is to provide comprehensive details on the carbon nanomaterials in oncology from the past two decades for patient compliance and safety.


Detection of intrahepatic veno-venous shunts by three-dimensional venography using multidetector-row computed tomography during angiography.
The hepatic vein (HV) can be removed during hepatectomy if there is an effective intrahepatic veno-venous shunt (vv-shunt). We evaluated the efficacy of vv-shunt detection by three-dimensional (3D) venography reconstructed from multidetector-row computed tomography (MDCT) during angiography. 3D venography was reconstructed using computer software in 88 patients with intrahepatic tumors. We found that 12 patients had one shunt [4 right hepatic vein (RHV)-middle hepatic vein (MHV) and 12 RHV- inferior right hepatic vein (IRHV)] and 1 patient had 2 shunts (RHV-MHV and -IRHV), confirming a clinically efficient vv-shunt in 14.8% of the patients. In one patient with an RHV-IRHV shunt, the preserved RHV-IRHV shunt worked well and prevented congestion of the postero-caudal subsegment after central bisegmentectomy with partial resection of the RHV ventral trunk for huge hepatocellular carcinoma (HCC). Although the vv-shunt detection rate by 3D venography is low, a visualized vv-shunt proved to be efficient. Thus, invasive occlusion venography is avoidable if a vv-shunt is seen on 3D venography.


Organ-specific effects on target binding due to knockout of thyroid hormone receptor α during Xenopus metamorphosis.
Thyroid hormone (T3) is essential for normal development and metabolism, especially during postembryonic development, a period around birth in mammals when plasma T3 levels reach their peak. T3 functions through two T3 receptors, TRα and TRβ. However, little is known about the tissue-specific functions of TRs during postembryonic development because of maternal influence and difficulty in manipulation of mammalian models. We have studied Xenopus tropicalis metamorphosis as a model for human postembryonic development. By using TRα knockout (Xtr·thratmshi ) tadpoles, we have previously shown that TRα is important for T3-dependent intestinal remodeling and hindlimb development but not tail resorption during metamorphosis. Here, we have identified genes bound by TR in premetamorphic wild-type and Xtr·thratmshi tails with or without T3 treatment by using chromatin immunoprecipitation-sequencing and compared them with those in the intestine and hindlimb. Compared to other organs, the tail has much fewer genes bound by TR or affected by TRα knockout. Bioinformatic analyses revealed that among the genes bound by TR in wild-type but not Xtr·thratmshi organs, fewer gene ontology (GO) terms or biological pathways related to metamorphosis were enriched in the tail compared to those in the intestine and hindlimb. This difference likely underlies the drastic effects of TRα knockout on the metamorphosis of the intestine and hindlimb but not the tail. Thus, TRα has tissue-specific roles in regulating T3-dependent anuran metamorphosis by directly targeting the pathways and GO terms important for metamorphosis.


Physiotherapeutical mistakes in the early stages after spinal cord injury.
To avoid paraosteoarthropathy no postural changes or passive movements should be done in the first 4 weeks after spinal cord injuries. Physiotherapists who are in charge of treatment of paraplegics should have a fundamental knowledge of spinal cord injuries to prevent such severe complications.


Effect of peripapillary tilt direction and magnitude on central visual field defects in primary open-angle glaucoma with high myopia.
To evaluate the relationship between peripapillary tilt and visual field (VF) defects in glaucomatous eyes with axial myopia. Retrospective cross-sectional study. One hundred four eyes of 104 patients with primary open-angle glaucoma (POAG) with myopia were included (52 eyes with high myopia [HM], 26.5 mm ≤ axial length [AL] < 30.0 mm; and 52 eyes without HM, 24.0 mm < AL < 26.5 mm). The direction and magnitude of the peripapillary tilt were evaluated using optical coherence tomography. The eyes were divided into 12 groups according to the tilt directions defined by clock-hour sectors in a clockwise direction in the right eyes and in a counterclockwise direction in the left eyes. The mean deviation (MD) and central VF (CVF) values, ie, the mean threshold values of 4 paracentral points within 5 degrees of the Swedish Interactive Threshold Algorithm 30-2 test, were evaluated. The direction of the tilt was toward sector 9 (47.1%) and sector 8 (34.6%). The MD and CVF values were significantly worse (P = 0.013 and P = 0.019, respectively) in the sector 9 group than in the sector 8 group. Furthermore, the smaller peripapillary tilt magnitude in the sector 9 group was negatively correlated (P = 0.0019) with the CVF but not with the MD (P = 0.1) among the POAG eyes with HM. In contrast, the ovality index in the sector 9 group was not significantly correlated with the MD (P = 0.4) or the CVF (P = 0.36). A smaller temporal peripapillary tilt correlated with CVF defects in POAG eyes with HM. The peripapillary tilt direction and magnitude affect the CVF defect in POAG eyes with HM.


Association of monocyte chemoattractant protein-1-2518A/G polymorphism and risk of coronary artery disease among the Chinese population: a meta-analysis.
Numerous studies have evaluated the association between the MCP-1-2518A/G polymorphism and coronary artery disease (CAD) risk; however, the actual association is controversial. To derive a more precise estimation of the relationship in Chinese population, we performed this meta-analysis. We searched the PubMed, Embase, Web of Science, and CNKI databases to identify studies that examined the association between the MCP-1-2518A/Gpolymorphism and the risk of CAD. We estimated the pooled odds ratio with its 95% confidence interval to assess this association. Seven studies containing 4024 Chinese subjects (2260 patients with CAD and 1764 controls) were included in this meta-analysis. MCP-1-2518A/G polymorphism was not found to be significantly associated with CAD risk in all comparisons (for G vs A: OR=1.10, 95% CI=0.92-1.32; for AG+GG vs AA: OR=1.10, 95% CI=0.79-1.53; for GG vs AA+AG: OR=1.05, 95% CI=0.91-1.21; for GG vs AA: OR=1.12, 95% CI=0.82-1.54; for AG vs AA: OR=1.05, 95% CI=0.76-1.47). Similarly, no associations were found in subgroup analysis based on source of control and endpoint. the MCP-1-2518A/G polymorphism was not associated with the risk of CAD in Chinese population.


Effect of administration route on the renal safety of contrast agents: a meta-analysis of randomized controlled trials.
The objective of this study was to examine the association between administration route and relative renal safety of contrast agents. We searched all published articles indexed in Embase, Medline and the Cochrane Central Register of Controlled Trials, from January 1980 to November 2010, to identify relevant studies. Of the 1,047 initially identified studies, 11 randomized controlled trials (RCTs) including 2,210 patients with intra-arterial route and 7 RCTs including 919 patients with intravenous route were finally analyzed. With regard to intra-arterial route, our meta-analysis showed that iodixanol significantly decreased the risk of contrast-induced acute kidney injury (CI-AKI) when compared with a pool of low-osmolar contrast media (LOCM; risk ratio [RR] = 0.68; 95% confidence interval [95% CI], 0.50-0.92; Z=2.47; p=0.01), with no significant heterogeneity between individual studies (p=0.14, I2=32.4%). However, iodixanol was not associated with a reduction in CI-AKI compared with the LOCM pooled together (RR=0.75; 95% CI, 0.44-1.26; Z=1.10; p=0.27) with intravenous application, again with no significant heterogeneity between individual studies (p=0.40, I2=3.6%). Our meta-analysis suggests that administration route may affect the renal safety of contrast agents. Specifically, iodixanol may be a better choice for patients in the interventional cardiology setting.


Skin anti-inflammatory activity of water-soluble fullerene nanocomposites encompassed by sodium hyaluronate.
Fullerene is one of the nanomaterials that has a value in dermatological and cosmetic applications. In present work, we designed and prepared water-soluble nano-scale C60 encompassed by sodium hyaluronate. The rat ear swelling test was utilized to evaluate the anti-inflammatory activity of encompassed C60. The measurement shows that the rat ear swelling rate of C60 administrated group is reduced to less than 10%, which shows good anti-inflammatory activity. Its anti-inflammatory activity is roughly calculated as 10 times than that of dipotassium glycyrrhizinate and five times than that of tanshinone. In conclusion, the fullerenes encapsulated by sodium hyaluronate have great potential in skin care and auxiliary treatment of dermatosis.


Serodiagnosis of parasitic infections by ELISA with different antigens.
An enzyme-linked immunosorbent assay is described in which four antibodies (amoebiasis, schistosomiasis, echinococcosis and filariasis) can be tested at once. Because of the sensitivity, specificity, reproducibility and practicability this test system can be recommended as a quantitative routine test.


Deep multiple instance learning for predicting chemotherapy response in non-small cell lung cancer using pretreatment CT images.
The individual prognosis of chemotherapy is quite different in non-small cell lung cancer (NSCLC). There is an urgent need to precisely predict and assess the treatment response. To develop a deep multiple-instance learning (DMIL) based model for predicting chemotherapy response in NSCLC in pretreatment CT images. Two datasets of NSCLC patients treated with chemotherapy as the first-line treatment were collected from two hospitals. Dataset 1 (163 response and 138 nonresponse) was used to train, validate, and test the DMIL model and dataset 2 (22 response and 20 nonresponse) was used as the external validation cohort. Five backbone networks in the feature extraction module and three pooling methods were compared. The DMIL with a pre-trained VGG16 backbone and an attention mechanism pooling performed the best, with an accuracy of 0.883 and area under the curve (AUC) of 0.982 on Dataset 1. While using max pooling and convolutional pooling, the AUC was 0.958 and 0.931, respectively. In Dataset 2, the best DMIL model produced an accuracy of 0.833 and AUC of 0.940. Deep learning models based on the MIL can predict chemotherapy response in NSCLC using pretreatment CT images and the pre-trained VGG16 with attention mechanism pooling yielded better predictions.


Morphometric analysis of corneal endothelium following radial keratotomy.
We performed morphometric analysis of the central corneal endothelium on 24 eyes of 19 patients who had had anterior radial keratotomy. The endothelium was analyzed for a variety of parameters, including cell area, perimeter, side lengths, cell shape, and number of sides. Mean, standard deviation, and coefficient of variation were calculated for each parameter. The mean cell density decreased from 2,835 to 2,677 cells/mm2, mean cell perimeter increased from 71.4 micron to 74.3 micron, and mean side length increased from 11.8 micron to 12.3 micron following surgery. The changes in these three parameters were statistically significant (P less than 0.05). The coefficient of variation of cell area (polymegathism) changed from 0.319 to 0.307, the hexagonality changed from 62.5% to 59.6%, and the cell shape changed from 0.872 to 0.867. The changes in these parameters were not statistically different before and after surgery. The group of patients that had no reported microperforations showed only a small decrease of cell density (1.6%), while the group of patients that had microperforations showed a large decrease of cell density (14.3%). The cell perimeter and side lengths showed a similar pattern. The group of corneas with the optical zone diameter less than 3.5 mm showed a decrease in mean cell density from 2,994 to 2,725 cells/mm2, and the cell shape changed from 0.874 to 0.866 following surgery. The changes in these parameters were statistically significant (P less than 0.05) before and after surgery. Among all factors associated with radial keratotomy, microperforation and a small diameter of central optical zone appear to be the two greatest risk factors.


Probing structural selectivity of synthetic heparin binding to Stabilin protein receptors.
As one of the most widely used drugs worldwide, heparin is an essential anticoagulant required for surgery, dialysis, treatment of thrombosis, cancer, and general circulatory management. Stabilin-2 is a scavenger clearance receptor with high expression in the sinusoidal endothelium of liver. It is believed that Stabilin-2 is the primary receptor for the clearance of unfractionated and low molecular weight heparins in the liver. Here, we identify the modifications and length of the heparin polymer that are required for binding and endocytosis by both human Stabilin receptors: Stabilin-2 and its homolog Stabilin-1 (also found in liver endothelium). Using enzymatically synthesized (35)S-labeled heparan sulfate oligomers, we identified that sulfation of the 3-OH position of N-sulfated glucosamine (GlcNS) is the most beneficial modification for binding and endocytosis via both Stabilin receptors. In addition, our data suggest that a decasaccharide is the minimal size for binding to the Stabilin receptors. These findings define the physical parameters of the heparin structure required for efficient clearance from blood circulation. These results will also aid in the design of synthetic heparins with desired clearance rates.


Obesity paradox and mortality in adults with and without incident type 2 diabetes: a matched population-level cohort study.
Among adults with type 2 diabetes (T2D), several (but not all) studies show that being overweight (body mass index (BMI): 25.0-29.9 kg/m2) or obese I (BMI: 30.0-34.9 kg/m2) near the time of diagnosis, is unexpectedly associated with reduced all-cause mortality compared with normal weight-the obesity paradox. We addressed whether this observation is causal (eg, a true protective effect); due to confounding (including effect modification); or due to selection ('collider') bias. We performed a matched population-level cohort study using primary care records from Salford, UK (1995-2012) in 10 464 patients with incident T2D paired (1:3) with 31 020 individuals who never developed T2D. We estimated HRs for associations of BMI with all-cause mortality using Cox models, stratified by smoking status. Median follow-up was 8.7 years. For never smokers, the hazard of all-cause mortality increased from 25 kg/m2, in a linear manner, with increasing BMI in the T2D cohort (HR per 5 kg/m2: 1.23, ptrend<0.001) and in the non-diabetes cohort (HR per 5 kg/m2: 1.34, ptrend<0.001). In contrast, among ever smokers, BMI-mortality relationships were U-shaped in the T2D and non-diabetes cohorts. Evidence of the obesity paradox in ever smokers, with and without T2D, argued against a selection bias, but supported a contribution of effect modification by smoking (pinteraction=0.009). Results were stable to various sensitivity analyses. In this cohort, the obesity paradox is mainly explained by smoking as an effect modifier. These findings indicate that the obesity paradox does not challenge standard weight management recommendations among T2D patients.


The interaction of ASAH1 and NGF gene involving in neurotrophin signaling pathway contributes to schizophrenia susceptibility and psychopathology.
The neurodevelopmental hypothesis of schizophrenia has been widely accepted. In light of our previous microarray data, two neurodevelopment-related genes were focused on inclduing the N-acylsphingosine amidohydrolase 1 gene (ASAH1) and the nerve growth factor gene (NGF). The evidence that ASAH1 and NGF are associated with schizophrenia is far from conclusive. Furthermore, their interactions in schizophrenia have not been investigated. Total 413 patients and 578 controls were included. Eleven single-nucleotide polymorphisms (SNPs) in ASAH1 and NGF were selected. A multifactor dimensionality reduction (MDR) was applied to investigate gene-gene interactions in schizophrenia, and the traditional odds ratio methods was applied to validate it. The effects of ASAH1, NGF and their interaction on the severity of the disease were analyzed by 3 × 3 covariance analysis of (ANCOVA). The biological interaction between ASAH1 and NGF was examined. KEGG was used to identify the related signaling pathways. After correction by Bonferroni, there were no differences in the genotypic, allelic, or haplotypic frequencies of 11 SNPs between patients and controls. However, the interaction of certain SNPs had effect on susceptibility to schizophrenia, including two high-risk and one low-risk genotypic combinations (OR = 1.49 [1.11-2.00]; OR = 1.45 [1.09-1.92], and OR = 0.64 [0.41-0.98]). ASAH1-rs7830490 and its interaction with NGF-rs4332358 were associated with the general psychopathological subscale score (F adjusted = 3.94, p adjusted = 0.01; F adjusted = 2.36, p adjusted = 0.03). We also found that ASAH1 and NGF interacted with CaMK2B involving in the neurotrophin signaling pathway. Our results suggest that the interaction of ASAH1 and NGF with CaMK2B involved in neurotrophin signaling pathway may contribute to schizophrenia susceptibility and psychopathology.


Assertive Communication in Condom Negotiation: Insights From Late Adolescent Couples' Subjective Ratings of Self and Partner.
Assertive communication has been associated with higher levels of condom use among youth using self-report survey methodology. The purpose of this study was to examine the subjective ratings of assertiveness among young, romantically involved couples in the context of a condom negotiation task. Using an innovative video-recall procedure, 32 couples (64 youth) engaged in a videotaped condom negotiation task and then rated self and partners' level of assertiveness. Both individual ratings of assertiveness and couple-level assertiveness were assessed using dyadic hierarchical linear modeling. Individuals' assertiveness was positively associated with condom use. Unexpectedly, the overall level of assertiveness in couples showed a curvilinear association with condom use. Very high and very low assertiveness was associated with lower condom use, whereas moderate levels of assertiveness were associated with higher condom use. Moderate levels of assertiveness during condom negotiation may facilitate condom use in young couples. Increasing condom use among romantic partners may require developing interventions that strengthen youths' ability to engage in assertive communication strategies that balance emotional intimacy with self-advocacy.


Quality of life in long-term survivors of out-of-hospital cardiac arrest.
The quality of life in long-term survivors of out-of-hospital cardiac arrest may be a good outcome measure after resuscitation. Therefore, the psychosocial situation and quality of life in such patients after successful resuscitation was evaluated. Patients with out-of-hospital cardiac arrest in a community referred to a single tertiary care centre were compared with matched controls. Quality of life was evaluated in 50 consecutive arrest cases (40 males, 10 females; 60+/-13 years) 5-68 months (mean 31.7) after resuscitation according to American Heart Association protocols. The Psychological General Well-being Index questionnaire indicated no significant differences in anxiety, depression, vitality, general well-being, or self-control between patients and controls. However, the Nottingham Health Profile questionnaire demonstrated significant decreases in physical mobility (14.5+/-18.1 vs. 4.0+/-8.5, P=0.0001), energy levels (25.3+/-31.0 vs. 2.0+/-8.0, P=0.0001), emotional reactions (11.3+/-16.6 vs. 4.0+/-10.2, P=0.009), and sleep patterns (19.2+/-28.6 vs. 8.4+/-16.7, P=0.023) in the arrest patients. Little differences were measured with the Everyday-Life Questionnaire. 49 of the 50 arrest patients judged their situation after resuscitation worth living; no significant changes in familial, and psychosocial parameters occurred. The quality of life was associated with few changes in psychosocial profile after successful resuscitation. The subjective negative factors bore little impact on the quality of daily living in our patients. Thus, continued efforts to improve out-of-hospital resuscitation measures for cardiac arrest are justified since long-term survivors can expect a good quality of life after successful resuscitation.


Doping and sports endocrinology: anabolic-androgenic steroids.
The use of anabolic steroids affects not only professional athletes but also the general population (bodybuilders, gym clients, and adolescents). In the first case, its use is prohibited and sanctioned by the World Anti-Doping Agency and Olympic committees. For the other users, it is difficult to establish its prevalence since many obtain the products via the internet. The reasons for its use are varied and different forms of use and other types of users have been described. Among the side effects of steroid use, hypogonadism is the most frequent cause for endocrinological consultation. After a general introduction to doping, this review describes the historical background of anabolic-androgenic steroids, their classification, forms of use, physiological effects, adverse effects on different organs and systems, treatment of hypogonadism, as well as detection methods.


Endocrine therapy of human breast cancer grown in nude mice.
Although there have been extensive studies of rodent breast tumor models, and of human breast cancer cell lines in culture, there is still need for a human tumor model which can be manipulated experimentally but also provides a valid expression of the tumor cells in a host environment. Athymic nude mice bearing transplanted human breast tumors have been proposed as such a model. This review therefore discusses the use of the athymic nude mouse model of the study of human breast cancer biology, and focuses on four subjects: 1. biological characteristics of heterotransplanted breast tumors; 2. endocrinology and pharmacology of hormonal agents in the nude mouse; 3. endocrine sensitivity of heterotransplanted tumors; and 4. applicability and limitations of this model for the study of human breast cancer.


Correlation between Sensing Accuracy and Read Margin of a Memristor-Based NO Gas Sensor Array Estimated by Neural Network Analysis.
Memristor-based gas sensors (gasistors) have been considered as the most promising candidate for detecting NO gas suitable for neural network (NN) analysis. In this work, in order to solve an overfitting issue arising from the training data when using a single gasistor, which degrades the accuracy of NN, we here propose a metal-insulator-silicon (MIS)-structured Zr3N4-based gasistor array that results in an improvement in both the accuracy of the NN analysis and the efficiency of the operating power. As a result, the proposed gasistor array showed a decrease of epoch and a 2.5% improvement of prediction accuracy at room temperature compared to single cells with metal/insulator/metal (MIM) and MIS structures. These results imply that an array structure based on MIS can efficiently solve the overfitting issue by receiving multiple responses at once, compared to a single gas sensor that obtains one response per sensing.


Bioreactors for Plant Embryogenesis and Beyond.
A variety of different bioreactors have been developed for use in initiating and cultivating somatic embryos. The various designs for embryogenesis and culture are critically evaluated here. Bioreactor optimization and operation methods are also described along with recommendations for use based on desired outcome.


Influence of borneol and muscone on geniposide transport through MDCK and MDCK-MDR1 cells as blood-brain barrier in vitro model.
The objective of this study was (1) to characterize geniposide transport through MDCK and MDCK-MDR1 cell lines to confirm its transport mechanism and (2) to evaluate the effect of borneol and muscone as enhancers of geniposide transport in the BBB models so as to explore the enhancement mechanism. Transport studies of geniposide were performed in both directions, from apical to basolateral and from basolateral to apical sides. Drug concentrations were analyzed by HPLC. Geniposide showed relatively poor absorption in MDCK and MDCK-MDR1 cells, apparent permeability coefficients ranging from 0.323×10(-6) to 0.422×10(-6) cm/s. The in vitro experiments showed that geniposide transport in both directions was not concentration dependent and saturable, indicating purely passive diffusion. The efflux ratio of geniposide was less than 2 in the two cell models, which suggested that geniposide was not P-gp substrates. Geniposide transport in both directions significantly increased when co-administrated with increasing concentrations of borneol and muscone. Actin staining results indicated that borneol and muscone increased geniposide transport in the BBB models may attribute to disassembly effect on tight junction integrity.


Serum hormonal concentrations following transcendental meditation--potential role of gamma aminobutyric acid.
Transcendental mediation (TM) is a stylized form of physical and mental relaxation which is associated with changes in the secretion and release of several pituitary hormones. The hormonal changes induced by TM mimic the effects of the inhibitory neurotransmitter gamma aminobutyric acid (GABA). It is hypothesized that TM produces changes in pituitary hormone secretion by enhancing hypothalamic GABAergic tone, and its anxiolytic effects by promoting GABAergic tone in specific areas of the brain. This mechanism is similar to the effects of synthetic anxiolytic and tranquilizing agents such as benzodiazepines that bind to components of the GABA-A (GABAA) receptor. TM, therefore, may produce relaxation by enhancing the effects of an endogenous neurotransmitter analogous to the effects of endorphins in runners who reportedly experience a 'runner's high'.


Multisystem Inflammatory Syndrome in Children and Kawasaki Disease: A Spectrum of Postinfectious Hyperinflammatory Disease.
Kawasaki disease and multisystem inflammatory syndrome in children are hyperinflammatory conditions that share similar emerging pathophysiology hypotheses, clinical features, treatment strategies, and outcomes. Although both conditions have key differences, growing evidence suggests that both conditions might be closely related on a larger spectrum of postinfectious autoimmune responses.


Analysis of the Agricultural Economy and Agricultural Pollution Using the Decoupling Index in Chengdu, China.
The development of the agricultural economy has brought the agricultural pollution, and agricultural pollution has restrained the growth of the agricultural economy and endangered public health. Since the Economic Reform opened up, China has promulgated many policies that have benefited farmers, developed the agricultural economy, and improved agricultural material levels. However, the growth in the agricultural economy has also resulted in significant environmental pollution from pesticides, agricultural fertilizers and agricultural plastic film. Agricultural pollution can affect public health, therefore it is necessary to study the relationship between agricultural economy and agricultural pollution. In this paper, the relationship between the agricultural economy and agricultural pollution is studied by using decoupling index method, taking Chengdu, Sichuan Province, China as an example, and verified by the data of 2008-2017 years of Chengdu. It was found that the decoupling index for pesticide use and per capita gross agricultural production showed "strong decoupling" ideal states in six years. From 2009-2017, the value of it increased from 0.065743-1.597385, and its decoupling state gradually transited to stable strong decoupling. The chemical fertilizer use was found to have a "strong decoupling" ideal state in five years. The value of it decreased from 1.028854-(-0.512702), while its state gradually changed to strong decoupling. However, agricultural plastic film only has one "strong decoupling" state with its value of decoupling index changed from -0.380824-(-0.250250). The increased use of plastic film has resulted in increased agricultural pollution. The research results show that growing with the development of Chengdu's agricultural economy, the use of pesticides and fertilizers has been decreasing. Chengdu's agricultural economy and agricultural pollution were found to have a healthy and coordinated development. The development of agricultural economy has not caused much damage to the agricultural environment. In addition, with the decline of agricultural pollution, public health problems will also be reduced.


Analysis of nucleotide pools in human lymphoma cells by capillary electrophoresis.
Capillary electrophoresis is applied to determine nucleotide pool levels in human Burkitt lymphoma cells. The analysis was performed on a 65 cm x 50 microns I.D. Ucon-coated column with on-column UV detector. The method requires only nanoliters of sample and a simple sample preparation procedure. Over 12 nucleotides were separated and quantitated with high resolution and reproducibility. The whole capillary electrophoretic separation time was only 35 min. These results demonstrate that capillary electrophoresis provides a useful and easy way to analyze nucleotide pools in cells.


Molybdenum cofactor deficiency type B knock-in mouse models carrying patient-identical mutations and their rescue by singular AAV injections.
Molybdenum cofactor deficiency is an autosomal, recessively inherited metabolic disorder, which, in the absence of an effective therapy, leads to early childhood death due to neurological deterioration. In type A of the disease, cyclic pyranopterin monophosphate (cPMP) is missing, the first intermediate in the biosynthesis of the cofactor, and a biochemical substitution therapy using cPMP has been developed. A comparable approach for type B of the disease with a defect in the second step of the synthesis, formation of molybdopterin, so far has been hampered by the extreme instability of the corresponding metabolites. To explore avenues for a successful and safe gene therapy, knock-in mouse models were created carrying the mutations c.88C>T (p.Q30X) and c.726_727delAA, which are also found in human patients. Recombinant adeno-associated viruses (rAAVs) were constructed and used for postnatal intrahepatic injections of MoCo-deficient mice in a proof-of-concept approach. Singular administration of an appropriate virus dose in 60 animals prevented the otherwise devastating phenotype to a variable extent. While untreated mice did not survive for more than 2 weeks, some of the treated mice grew up to adulthood in both sexes.


Targeting of envelope domain III protein of DENV type 2 to DEC-205 receptor elicits neutralizing antibodies in mice.
Dengue virus (DENV) is the causal agent of severe disease and, in some cases, mortality in humans, but no licensed vaccines against dengue are available. An effective vaccine against dengue requires long-term humoral and cellular immune responses. Several viral proteins have been the subjects of intense research, especially the envelope (E) protein, aimed at developing a vaccine. Domain III of the envelope protein (EDIII) has been identified as a potential candidate because it is involved in binding to host cell receptors and contains epitopes that elicit virus neutralizing antibodies. However, this domain is not sufficiently antigenic when is expressed and administered as antigen to elicit a strong immune response. One alternative to enhance immunogenicity is to target the antigen to dendritic cells to induce T-cells for broad antibody responses. In this work, a single chain antibody fragment (scFv) raised against the DEC-205 receptor fused with the EDIII was successfully expressed in Nicotiana benthamiana. The recombinant protein was expressed and purified from the plant and evaluated in BALB/c mice to test its immunogenicity and ability to induce neutralizing antibodies against DENV. The mice immunized with the recombinant protein produced specific and strong humoral immune responses to DENV. Only two immunizations were required to generate a memory response to DENV without the presence of adjuvants. Also, recognition of the recombinant protein with sera from DENV-infected patients was observed. These findings suggest that this strategy has potential for development of an effective vaccine against DENV.


Defluoridation of water by Tea-bag model using La(3+) modified synthetic resin@chitosan biocomposite.
The aim of this work is to gain a better understanding of the formation of lanthanum complex onto iminodiacetic acid and chitosan (CS@La-IDAMP) composite for effective removal of fluoride from aqueous solution using a tea-bag model for the first time. The surface textural and chemical properties of the synthesized composites were characterized by FTIR, SEM with EDAX and mapping images. The experimental data revealed that the fluoride adsorption was rapid, maximum fluoride removal could be removed within 12min contact time at neutral pH in room temperature under batch equilibrium model. The equilibrium data for adsorption of fluoride on the synthesized blends were well represented by the Freundlich isotherm, giving a maximum adsorption capacity of 17.50mg/g. The adsorption kinetic models were also examined and it was found that all the sorption processes were better described by the pseudo-second-order model. This results suggested that the efficiency of the fluoride removal process was mainly controlled by electrostatic attraction and ion-exchange mechanism. Furthermore, the CS@La-IDAMP material was tested for the regeneration ability with the suitable regenerant to make this process as cost-effective. Finally, it can be concluded that the composite material is the potential adsorbent for the treatment of fluoride from water.


Camptothecins: a review of their development and schedules of administration.
Used for centuries in traditional Chinese medicine, camptothecin was rediscovered in the 1950s during a search for compounds that could be used as a source for steroid synthesis. Due to its limited water solubility, a sodium salt was used in the early clinical trials. The severe toxicity and erratic absorption relegated this compound to the research laboratory until the 1980s when the topoisomerase enzyme was identified as the cellular target of camptothecin, the topoisomerase enzyme was found to be overexpressed in cancer cells and a structure-activity relationship was determined for camptothecin. These new developments brought the camptothecins back to the clinical setting for further testing. The various analogues that have been most studied to date include: irinotecan (CPT-11), and its derivative SN-38, topotecan, and 9-aminocamptothecin. Numerous trials have been conducted in an attempt to establish the efficacy in various tumour types, to determine the dose-limiting toxicity and to define the optimal schedule of administration. It seems that large doses of these drugs given on intermittent schedules are not effective. Our hypothesis is that the camptothecins require a prolonged schedule of administration given continuously at low doses or frequent intermittent dosing schedules to be most effective. With these schedules, normal haematopoietic cells and mucosal progenitor cells with low topoisomerase I levels may be spared, while efficacy is preserved.


COVID-19, lifestyle behaviors and mental health: A mixed methods study of women 6 months following a hypertensive pregnancy.
The COVID-19 pandemic introduced unprecedented challenges to both the physical and psychological health of postpartum women. The aim of this study was to determine how the COVID-19 pandemic affected the diet, physical activity and mental health of women 6 months following a hypertensive disorder of pregnancy. Mixed methods sub-study of the Blood Pressure Postpartum trial, which recruited women following a hypertensive disorder of pregnancy from six Sydney metropolitan hospitals. Cross sectional analysis of baseline quantitative data, collected at 6-months postpartum from March 2019-February 2022, and qualitative data analysis from semi-structured telephone interviews, was performed. Dates of COVID-19 lockdowns for Sydney, Australia were collected from government websites. Diet (vegetable, fruit, alcohol, take away intake) and physical activity (walking, vigorous activity, strength training frequency and duration) were assessed using the self-report NSW Population Health Survey. Depression and anxiety were assessed using the Edinburgh Depression Scale and GAD-7 scale, respectively. Outcome data were compared between women who completed surveys "In Lockdown" vs. "Not in Lockdown" as well as "Prior to any Lockdown" vs. "During or Following any Lockdown". Of 506 participants, 84 women completed the study surveys "In Lockdown," and 149 completed the surveys "Prior to any Lockdown." Thirty-four participants were interviewed. There were no statistically significant differences in diet, physical activity, depression and anxiety among women who completed the survey "In Lockdown" vs. "Not in Lockdown." "Prior to any Lockdown," participants were more likely to do any walking (95% vs. 89%, p = 0.017), any vigorous activity (43% vs. 30%, p = 0.006) or any strength training (44% vs. 33%, p = 0.024), spent more time doing vigorous activity (p = 0.003) and strength training (p = 0.047) and were more likely to drink alcohol at least monthly (54% vs. 38%, p < 0.001) compared with "During or Following any Lockdown." Our findings suggest that the confinements of lockdown did not markedly influence the mental health, diet and physical activity behaviors of women 6 months following hypertensive pregnancy. However, physical activity levels were reduced following the emergence of COVID-19, suggesting targeted efforts may be necessary to re-engage postpartum women with exercise. https://anzctr.org.au/Trial/Registration/TrialReview.aspx?id=376286&isReview=true, identifier: ACTRN12618002004246.


The effect of exercise training on ankle-brachial index in type 2 diabetes.
Though being physically active has associated with a healthier ankle-brachial index (ABI) in observational studies, ABI usually does not change with exercise training in patients with peripheral artery disease (PAD). Less is known about the effect of exercise training on ABI in patients without PAD but at high risk due to the presence of type 2 diabetes (T2DM). Participants (n = 140) with uncomplicated T2DM, and without known cardiovascular disease or PAD, aged 40-65 years, were randomized to supervised aerobic and resistance training 3 times per week for 6 months or to a usual care control group. ABI was measured before and after the intervention. Baseline ABI was 1.02 ± 0.02 in exercisers and 1.03 ± 0.01 in controls (p = 0.57). At 6 months, exercisers vs. controls improved ABI by 0.04 ± 0.02 vs. -0.03 ± 0.02 (p = 0.001). This change was driven by an increase in ankle pressures (p < 0.01) with no change in brachial pressures (p = 0.747). In subgroup analysis, ABI increased in exercisers vs. controls among those with baseline ABI <1.0 (0.14 ± 0.03 vs. 0.02 ± 0.02, p = 0.004), but not in those with a baseline ABI ≥1.0 (p = 0.085). The prevalence of ABI between 1.0 and 1.3 increased from 63% to 78% in exercisers and decreased from 62% to 53% in controls. Increased ABI correlated with decreased HbA1c, systolic and diastolic blood pressure, but the effect of exercise on ABI change remained significant after adjustment for these changes (β = 0.061, p = 0.004). These data suggest a possible role for exercise training in the prevention or delay of PAD in T2DM, particularly among those starting with an ABI <1.0. Clinicaltrials.gov Registry Number: NCT00212303.


App-Based Pain Management and Opioid Education Program for Patients in Clinic Waiting Rooms.
Best approaches to delivering patient education related to pain management and opioid safety are understudied. This study assessed the feasibility, acceptability, and preliminary patient-reported impact of an app-based patient pain education program. Pilot study with data collection occurring on 43 weekdays between August 2019-February 2020. Waiting rooms at the pain clinic and a primary care medical home within two military treatment facilities. Military health system beneficiaries seeking general care at the primary care medical home or pain-specific care at the pain clinic. The Joint Pain Education and Project curriculum includes patient-focused videos describing the biopsychosocial aspects of pain and pain management, medication take-back and safe disposal, and multidimensional pain assessments. The app-based videos were available on tablets in the waiting rooms for patients to view and complete surveys on after. Overall, 152 patients viewed the videos and completed surveys. Most viewers were interested in receiving other tablet-based health education while in the waiting room (62%). Most viewers found videos to be moderately or very helpful (73%) and were satisfied or very satisfied with the information provided (85%). Participants at the primary care medical home were more likely to find videos helpful compared to participants at the pain clinic (OR = 2.11; 95% CI: 1.07, 4.20; p = .03). Implementing app-based pain management education is feasible across clinic settings and is well received by patients. Clinics should consider providing pain education across care setting, rather than just pain specialty clinics, to help foster discussions between clinicians and patients regarding pain management and opioid safety.


Informed consent for the neurosurgeon.
Obtaining informed consent from patients contemplating neurosurgical procedures is an important process in preoperative care. A surgeon's failure to fulfill his or her legally prescribed duty to inform the patient and obtain consent can result in unnecessary exposure to liability. This paper describes the legal background, doctrine, and elements of informed consent. It also outlines the dialog that should legally take place between physician and patient before a planned procedure and discusses special circumstances that may affect the informed consent process.


Dissolution behavior of cellulose in a novel cellulose solvent.
We have found that cellulose can be dissolved rapidly in the mixed solvent of tetrabutylammonium acetate (TBAA) and a polar aprotic solvents (PAS) at 50 °C and the obtained cellulose solution could be regenerated into cellulose film and fiber. The factors affecting the dissolution behavior of cellulose were investigated and it was found that the solubility and dissolution rate of cellulose in the mixed solvent are significantly dependent on the species of PAS and the molar ratio of PAS/TBAA. The suitable PAS are dimethyl sulfoxide, pyridine, dimethylacetamide, dimethylformamide and N-Methyl-2-pyrrolidone, and dimethyl sulfoxide is the best one in regard to the solubility and dissolution rate of cellulose. The optimal molar ratio of PAS/TBAA was determined by DN of the polar aprotic solvents. The dissolution behaviour of cellulose in the mixed solvent was proposed to involve the solvent diffusion, solvation of TBA+ as well as disruption of the intermolecular or intramolecular hydrogen bonds of cellulose.


Apico-Aortic Conduit for severe aortic stenosis: Technique, applications, and systematic review.
Patients referred for aortic valve replacement are often elderly and may have increased surgical risk associated with ascending aortic calcification, left ventricular dysfunction, presence of coronary artery disease, previous surgery, and/or presence of several co-morbidities. Some of these patients may not be considered candidates for conventional surgery because of their high risk profile. While transcatheter aortic valve replacement constitutes a widely accepted alternative, some patients may not be eligible for this modality due to anatomic factors. Apico-Aortic Conduit (AAC) insertion (aortic valve bypass surgery) constitutes a possible option in those patients. Apico-Aortic Conduit is not a new technique, as it has been used for decades in both pediatric and adult populations. However, there is a resurging interest in this technique due to the expanding scope of elderly patients being considered for the treatment of aortic stenosis. Herein, we describe our surgical technique and provide a systematic review of recent publications on AAC insertion, reporting that there is continued use and several modifications of this technique, such as performing it through a small thoracotomy without the use of the cardiopulmonary bypass.


Enteral Nutrition: The Intricacies of Human Milk from the Immune System to the Microbiome.
In 2012, the American Academy of Pediatrics stated that all preterm infant diets should consist of human milk (mother's own milk or pasteurized donor human milk). The clinical reasons supporting this policy are many, including reducing infections and retinopathy of prematurity, decreased neonatal intensive care unit length of stay, subsequent readmissions, a decrease in mortality, and improved neurodevelopmental outcomes. This article focuses on human milk, its composition and bioactive factors, and how it affects the gut-brain axis through the microbiome. We examine how differences between mother's own milk and pasteurized donor human milk affect the premature infant.


[Effect of the imidazoline receptor agonist moxonidine on hemodynamics, coronary circulation, metabolic ischemia markers and the neurohumoral system in patients with essential hypertension. Effects of moxonidine on coronary circulation].
Moxonidine is a new centrally active imidazoline-receptor agonist being effectively applied in the treatment of arterial hypertension due to its sympathicolytic potency. This is the first investigation regarding the effects of moxonidine on coronary and systemic hemodynamics, metabolic markers of ischemia and neurohumoral parameters in patients with essential hypertension (WHO I-II). We studied moxonidine (single dose of 0.4 mg p.o.) in 22 patients with left ventricular (LV) hypertrophy, ST segment depressions during exercise, pectanginal complaints and negative coronarograms. Assessments included arterial blood pressure, cardiac output, pulmonary artery pressure mean (PAPm), pulmonary capillary wedge pressure (PCWP) and coronary sinus flow (CSF) by intravascular Doppler technique. The moxonidine-induced parameter changes 2 hours later were as follows: a decrease in systolic/diastolic pressure by 28/10 mmHg, and in heart rate by 5 bpm, associated with a decline of PAPm by 17% and of PCWP by 26%. LV work was reduced by 26%, MVO2 by 18% and CSF by 16%. Average peak velocity in CS fell by 18% and coronary flow reserve (with adenosine) increased by 12%. CS-O2 saturation rose by 4%, accompanied by an increase in lactate extraction by 17%, a decrease in norepinephrine spillover by 30% and in arterial endotheline by 20%. In conclusion, moxonidine produces clinically relevant sympathicolysis with beneficial effects on hemodynamics, coronary circulation and neurohumoral parameters.


A profile of heart disease risk factors and their relation to parents' education, fathers' occupation and family history of heart disease in 843 South Australian families: the Adelaide Children's WHO Collaborative Study.
A study was conducted to determine whether the prevalence of risk factors among pre-adolescent children is associated with their parents' risk factor status and what influence family history of ischaemic heart disease (IHD) and socio-economic status (SES) had. This was a cross-sectional study of 856 children, mean age 8.6 years, and their parents who underwent the World Health Organization and National Heart Foundation protocols for the study of arteriosclerosis precursors. Historical, demographic, anthropometric, clinical and biochemical outcome measures were used. There was the expected burden of illness reported for the grandparents and parents, with the latter conforming to their expected age group's heart disease risk factor status. The mean serum total cholesterol (TC) level for boys was 4.43 (+/- 0.79) mmol/L and girls 4.62 (+/- 0.84) mmol/L, with the 95th percentile for boys and girls combined being 5.88 mmol/L. The level corresponding to two standard deviations above the mean was 6.0 mmol/L. Childrens' IHD risk factor status reflected their parents' with TC, skin fold thickness and body mass index most closely correlated, followed by blood pressure. The greatest correlation was between the childrens' TC and their mothers'. Socio-economic status as assessed by the parents' education level and fathers' occupational status produced differences in their childrens' risk factors, with mother's level of education having the major influence. There was no impact of family history of IHD. From these results it would appear that screening of the pre-adolescent may be appropriate but longitudinal study will be important to establish this by documenting persistence of risk factor status. Also, it would appear that a child's future risk from IHD morbidity may be due to environmental influences mediated through differences in SES. As the level of IHD risk factors is reduced within the community, the extent of parent-child transmission of measurable IHD risk factors in families of high IHD risk may be reduced.


Fatal varicella in steroid-dependent asthma.
Disseminated varicella infection is a potentially life-threatening complication of chronic high-dose corticosteroid (CS) or immunosuppressive therapy. A review of the literature indicates that, with one possible exception, this complication has not occurred in a CS-dependent subject with asthma. We present in this article the clinical features and autopsy findings of a steroid-dependent subject with asthma who died of acute, disseminated varicella. A 16-year-old poorly compliant, steroid-dependent subject with asthma received two courses of high-dose intravenous methylprednisolone during a 3-week period, followed by a tapering schedule of oral prednisone. During this time, she was exposed to chickenpox. She subsequently developed a classic varicella rash, sever back pain, rapidly progressive hepatic failure, pneumonitis, and encephalopathy. Death ensued 3 days after the onset of the rash. Evidence of disseminated varicella infection was confirmed at autopsy. This case illustrates that a small number of subjects with severe asthma receiving high-dose CS need to be considered as a separate, high-risk group for developing disseminated varicella. We recommend that the immune status of these patients to varicella-zoster virus be assessed by a serum titer. If these patients are nonimmune, they would be candidates for varicella-zoster immune globulin on exposure, and for acyclovir therapy should varicella dissemination occur.


Doppler ultrasound monitoring of systemic blood flow during CPR.
During cardiopulmonary resuscitation in 12 patients, Doppler ultrasound monitoring of radial arterial flow provided an audible, instantaneous flow sound to which the resuscitation team referred, along with the monitor electrocardiogram (EKG), in determining hemodynamic status. Incidental to the resuscitation effort, a separate analog flow signal and the monitor EKG were simultaneously recorded in eight patients. Doppler blood flow monitoring allowed evaluation of effectiveness of cardiac massage; immediate recognition of electromechanical dissociation; rapid determinations of blood pressure, often during profound hypotension, and estimates of changes in cardiac output. When the hemodynamic consequences were immediately obvious, both ineffective chest compression and pauses longer than five seconds during effective chest compression were not tolerated by those in attendance, for whom the Doppler flow signal often became the primary reference in determining the patient's cardiac status.


Arrested pneumatization of sinus sphenoid, revealed by hypo-acusis: A case report.
The sphenoid bone is a complex structure in terms of its embryological origin. At birth, the sphenoid sinus is not pneumatised. Pneumatisation begins at around 4 months of age until the age of 12-14 years. If this process is absent or interrupted for reasons that are often unknown, it is called arrested pneumatisation. This report describes the case of a 15 year old patient, who consulted an ENT specialist for chronic headaches and hearing loss on the left side. Clinical ENT examination (including otoscopy) is normal. Tonal audiometry revealed a sensorineural hearing loss in the left ear. A CT scan of the petrous bone was normal but revealed a hypodense lesion in the left sphenoid bone. Lipoma was suggested. A brain MRI was performed in a clinic to better characterize the lesion. MR images showed a well-defined lesion with fatty content. The diagnosis was nasosinus fibrous dysplasia. In view of the diagnostic discrepancy, the patient was referred to our department for a specialist opinion. An additional brain scan revealed a non-eroded, non-expansive fatty density lesion with well-defined internal curvilinear calcification in the left sphenoid sinus location. Our final diagnosis was arrested pneumatisation. Most patients with arrested pneumatization of the skull base are asymptomatic. Sometimes it may be revealed by nonspecific signs and be confused with severe skull base disease, especially if the radiologist is not familiar with its existence or its typical features.


Stabilization of beta-propeller phytase by introducing Xaa-->Pro and Gly-->Ala substitutions at consensus positions.
Phytases play important roles in agricultural and feed industries. In this study, the stability of a beta-propeller phytase, PhyL, from Bacillus licheniformis was successfully improved by introducing Xaa-->Pro and Gly-->Ala substitutions at consensus positions. Our results suggest that Gly-->Ala substitution is a more promising strategy to improve protein stability.


Levuglandin E2 crosslinks proteins.
Levuglandin E2 (LGE2), a gamma-ketoaldehyde produced by rearrangement of the prostaglandin endoperoxide PGH2 under the aqueous conditions of its biosynthesis, causes extensive intermolecular crosslinking of ovalbumin at pH 6 or pH 7 and 37 degrees C. The time dependence of protein oligomerization is monitored by SDS-PAGE. Effects of pH and concentration on the extent of LGE2-induced crosslinking are examined. The efficacy of LGE2 for inducing crosslinking is compared with other oxidative metabolites of arachidonic acid (AA), including the prostaglandins PGE2, PGD2, PGA2, PGB2, and PGF2 alpha, as well as malondialdehyde and E-4-hydroxy-non-2-enal. LGE2 is orders of magnitude more effective in crosslinking protein than any other cyclooxygenase or lipoxygenase metabolite of AA tested.


Perturbation of intracellular pH by DIDS on endocytosis of transferrin and iron uptake in rabbit reticulocytes.
DIDS (4,4'-diisothiocyanostilbene-2,2'-disulfonic acid) inhibited transferrin and iron uptake by rabbit reticulocytes in a dose-dependent manner. Measurement of intracellular pH shows that DIDS neutralized the pH in the intracellular vesicles and at the same time, rendered the cytoplasmic pH more acidic. The latter may be the result of a perturbance in the acid-extruding mechanism(s) by DIDS, a known anion exchange blocker. Examination of the single-cycle endocytosis of transferrin with pulse-chased technique suggests that DIDS retarded transferrin internalization, iron unloading and transferrin receptor recycling in the cells.


Human squamous cell carcinoma lines express oncofetal 44-kD polypeptide defined by monoclonal antibody to mouse fetus.
Most primary human carcinomas uniformly express an oncofetal epitope which has not been demonstrated previously in established human carcinoma cell lines. We successfully derived several low-passage cell lines of human squamous cell carcinoma (SCC) from head and neck tumors using an in vitro adaptation procedure, characterized these lines, and examined them for expression of a 44-kilodalton (kD) polypeptide (PP) oncofetal antigen (OFA) at the cell surface. Newly established an in vitro-passaged SCC cells retained characteristic microvilli, numerous desmosomes and tonofilaments, abundant rough endoplasmic reticulum, osmophilic keratohyaline granules, and other features of the primary SCC cells. These new cell lines and two long-term, established SCC lines (FaDu and Detroit 562) displayed OFA at the cell surface, as determined by flow cytometry using monoclonal antibody (MoAb) 115. While the FaDu and Detroit 562 lines exhibited aneuploidy during flow cytometric analysis, the new, low-passage SCC lines that we developed remained diploid as were the primary SCC cells from which they were derived. We propose that the expression of a 44-kD OFA is a common feature of human SCC. This marker may prove useful in the detection and treatment of these tumors.


Animal-habitat relationships in the Knysna Forest, South Africa: discrimination between forest types by birds and invertebrates.
Effects of forest plant species composition and physiognomy on bird and invertebrate communities were investigated in three discrete, relatively undisturbed forest types along a dry-wet soil moisture gradient. Using discriminant function analysis, a 100% floristic and a 78% vegetation structural discrimination were obtained between the three forest types. However, the bird communities of these different forest types were very similar in species composition, and had much lower densities than those normally encountered in other, superficially similar forests. Although an 81% discrimination between forest types was attained through analysis of ground surface invertebrates, measures of litter and aerial invertebrate abundance were also of limited use as discriminators. Historical and biogeographic factors, as well as the low nutritional levels in the soil and vegetation may be the causes of low bird and invertebrate density and diversity. It is concluded that floristics and vegetation structure have, at best, a minor influence on bird community structure, and possibly also on invertebrate community structure in the Knysna Forest.


Rapid expansion of human cytotoxic T cell clones: growth promotion by a heat-labile serum component and by various types of feeder cells.
Culture conditions are described that result in rapid expansion of cloned cytotoxic T cells of human origin. A combination of allogeneic lymphocytes and Epstein-Barr virus (EBV) transformed B cells (B-LCL) as irradiated feeder cells resulted in a 10-fold higher cell yield than obtained by use of either feeder cell alone. The large cell numbers obtained in a relatively short period of time facilitate in vitro and in vivo experimentation. Further enhancement of cell proliferation was obtained by the use of fresh human serum not heat-inactivated before use. This suggests the presence of a heat-labile growth stimulating factor or factors in human serum. Round-bottomed microtitre wells were found to give best culture results. Plating and harvesting of cells cultured in wells was facilitated by a specially designed culture flask. Addition of leucoagglutinin (purified phytohaemagglutinin) to the culture medium resulted in an approximately 3-fold higher cell yield. Optimal culture results were obtained when all the above factors were combined. It was possible to expand single cytotoxic T cells to up to 10(9) cells in about 30 days with full retention of cytolytic activity and target cell specificity. T cell clones have now been cultured for more than 70 generations.


Sublingual microcirculatory alterations during the immediate and early postoperative period: A systematic review and meta-analysis.
The incidence of postoperative microcirculatory flow alterations and their effect on outcome have not been studied extensively. This systematic review and meta-analysis were designed to investigate the presence of sublingual microcirculatory flow alterations during the immediate and early postoperative period and their correlation with complications and survival. A systematic search of PubMed, Scopus, Embase, PubMed Central, and Google Scholar was conducted for relevant articles from January 2000 to March 2021. Eligibility criteria were randomized controlled and non-randomized trials. Case reports, case series, review papers, animal studies and non-English literature were excluded. The primary outcome was the assessment of sublingual microcirculatory alterations during the immediate and early postoperative period in adult patients undergoing surgery. Risk of bias was assessed with the Ottawa-Newcastle scale. Standard meta-analysis methods (random-effects models) were used to assess the difference in microcirculation variables. Thirteen studies were included. No statistically significant difference was found between preoperative and postoperative total vessel density (p = 0.084; Standardized Mean Difference (SMD): -0.029; 95%CI: -0.31 to 0.26; I2 = 22.55%). Perfused vessel density significantly decreased postoperatively (p = 0.035; SMD: 0.344; 95%CI: 0.02 to 0.66; I2 = 65.66%), while perfused boundary region significantly increased postoperatively (p = 0.031; SMD: -0.415; 95%CI: -0.79 to -0.03; I2 = 37.21%). Microvascular flow index significantly decreased postoperatively (p = 0.028; SMD: 0.587; 95%CI: 0.06 to 1.11; I2 = 86.09%), while no statistically significant difference was found between preoperative and postoperative proportion of perfused vessels (p = 0.089; SMD: 0.53; 95%CI: -0.08 to 1.14; I2 = 70.71%). The results of the non-cardiac surgery post-hoc analysis were comparable except that no statistically significant difference in perfused vessel density was found (p = 0.69; SMD: 0.07; 95%CI: -0.26 to 0.39; I2 = 0%). The included studies investigate heterogeneous groups of surgical patients. There were no randomized controlled trials. Significant sublingual microcirculatory flow alterations are present during the immediate and early postoperative period. Further research is required to estimate the correlation of sublingual microcirculatory flow impairment with complications and survival.


IFN-α/β-mediated NK2R expression is related to the malignancy of colon cancer cells.
Neurokinin 2 receptor (NK2R), a G protein-coupled receptor for neurokinin A (NKA), a tachykinin family member, regulates various physiological functions including pain response, relaxation of smooth muscle, dilation of blood vessels, and vascular permeability. However, the precise role and regulation of NK2R expression in cancer cells have not been fully elucidated. In this study, we found that high NK2R gene expression was correlated with the poor survival of colorectal cancer patients, and Interferon (IFN-α/β) stimulation significantly enhanced NK2R gene expression level of colon cancer cells in a Janus kinas 1/2 (JAK 1/2)-dependent manner. NKA stimulation augmented viability/proliferation and phosphorylation of Extracellular-signal-regulated kinase 1/2 (ERK1/2) levels of IFN-α/β-treated colon cancer cells and NK2R blockade by using a selective antagonist reduced the proliferation in vitro. Administration of an NK2R antagonist alone or combined with polyinosinic-polycytidylic acid, a synthetic analog of double-stranded RNA, to CT26-bearing mice significantly suppressed tumorigenesis. NK2R-overexpressing CT26 cells showed enhanced tumorigenesis and metastatic colonization in both lung and liver after the inoculation into mice. These findings indicate that IFN-α/β-mediated NK2R expression is related to the malignancy of colon cancer cells, suggesting that NK2R blockade may be a promising strategy for colon cancers.


The effects of expectancy, professional identity, and behavior upon social rejection.
Psychiatric residents (n = 16) and undergraduate students (n = 32) listened to four recorded interviews. Each interview was designed to represent a particular combination of impulse control and distress. Two levels of mental illness expectancy were obtained by changing the context of the interviews. The subjects rated the interviewees on scales of social acceptance and psychopathology. Univariate analyses of variance were used to evaluate the data. The evidence indicated that an individual's behavior must be actually perceived as psychopathological before social rejection will occur.


GPURFSCREEN: a GPU based virtual screening tool using random forest classifier.
In-silico methods are an integral part of modern drug discovery paradigm. Virtual screening, an in-silico method, is used to refine data models and reduce the chemical space on which wet lab experiments need to be performed. Virtual screening of a ligand data model requires large scale computations, making it a highly time consuming task. This process can be speeded up by implementing parallelized algorithms on a Graphical Processing Unit (GPU). Random Forest is a robust classification algorithm that can be employed in the virtual screening. A ligand based virtual screening tool (GPURFSCREEN) that uses random forests on GPU systems has been proposed and evaluated in this paper. This tool produces optimized results at a lower execution time for large bioassay data sets. The quality of results produced by our tool on GPU is same as that on a regular serial environment. Considering the magnitude of data to be screened, the parallelized virtual screening has a significantly lower running time at high throughput. The proposed parallel tool outperforms its serial counterpart by successfully screening billions of molecules in training and prediction phases.


Increase of the prostaglandin precursor, arachidonic acid, in amniotic fluid during spontaneous labour.
Concentrations of free arachidonic acid have been measured by gas liquid chromatography in amniotic fluid obtained during spontaneous labour at term. Levels of arachidonic acid ranged from 0.14 to 2.9 microgram/ml and increased significantly (P less than 0.01) with advancing cervical dilatation. Concentrations of arachidonic acid showed no significant relation to concentrations of either prostaglandin F or 13,14-dihydro-15-keto-prostaglandin F. These findings are discussed with respect to the role of arachidonic acid in the control of prostaglandin biosynthesis during human parturition.


A new dosing regimen of ropeginterferon alfa-2b is highly effective and tolerable: findings from a phase 2 study in Chinese patients with polycythemia vera.
Ropeginterferon alfa-2b represents a new-generation pegylated interferon-based therapy and is administered every 2-4 weeks. It is approved for polycythemia vera (PV) treatment in the United States and Europe with a starting dose of 100 µg (50 µg for patients receiving hydoxyurea) and intra-patient dose titrations up to 500 µg at 50 µg increments, which took approximately 20 or more weeks to reach a plateau dose level. This study aimed to assess ropeginterferon alfa-2b at an alternative dosing regimen with a higher starting dose and quicker intra-patient dose titrations, i.e., the 250-350-500 μg schema, in 49 Chinese patients with PV with resistance or intolerance to hydroxyurea. The primary endpoint of the complete hematologic response rate at treatment weak 24 was 61.2%, which was notably higher than 43.1% at 12 months with the approved dosing schema. The JAK2V617F allele burden decreased from baseline to week 24 (17.8% ± 18.0%), with one patient achieving a complete molecular response. Ropeginterferon alfa-2b was well-tolerated and most adverse events (AEs) were mild or moderate. Common AEs included alanine aminotransferase and aspartate aminotransferase increases mostly at grade 1 or 2 levels. Patients did not present with jaundice or significant bilirubin level increase. No grade 4 or 5 AEs occurred. Seven patients (14.3%) experienced reversible, drug-related grade 3 AEs. No AEs led to treatment discontinuation. Ropeginterferon alfa-2b at the 250-350-500 μg regimen is highly effective and well-tolerated and can help patients achieve greater and rapid complete hematologic and molecular responses.Clinical Trial Registration: This trial is registered at ClinicalTrials.gov (Identifier: NCT05485948) and in China (China National Medical Products Administration Registration Number: CTR20211664).


[Omphalourachitis with abscess of the urachus and rectal prolapse in a llama cria (Lama glama)].
This case report describes the diagnosis and therapy of an omphalo-urachitis in a llama cria. Additionally, the cria developed a rectal prolapse, which was successfully treated with a temporary pararectal tobacco pouch suture following umbilical surgery.


Human ribosomal protein L4: cloning and sequencing of the cDNA and primary structure of the protein.
The cloning and sequencing of a cDNA for human ribosomal protein L4 is reported. The corresponding mRNA has a very short 5' untranslated region initiating with a sequence of 12 pyrimidines, characteristic of all vertebrate ribosomal protein mRNAs. The deduced amino acid sequence shows that human ribosomal protein L4 has 425 amino acid residues and a calculated molecular mass of 47,821 Da. Comparison with the homologous counterparts of Xenopus, Drosophila and yeast shows that this protein has a very conserved amino-terminus region and an extremely divergent carboxyl-terminus portion.


Gut bacterial isoamylamine promotes age-related cognitive dysfunction by promoting microglial cell death.
The intestinal microbiome releases a plethora of small molecules. Here, we show that the Ruminococcaceae metabolite isoamylamine (IAA) is enriched in aged mice and elderly people, whereas Ruminococcaceae phages, belonging to the Myoviridae family, are reduced. Young mice orally administered IAA show cognitive decline, whereas Myoviridae phage administration reduces IAA levels. Mechanistically, IAA promotes apoptosis of microglial cells by recruiting the transcriptional regulator p53 to the S100A8 promoter region. Specifically, IAA recognizes and binds the S100A8 promoter region to facilitate the unwinding of its self-complementary hairpin structure, thereby subsequently enabling p53 to access the S100A8 promoter and enhance S100A8 expression. Thus, our findings provide evidence that small molecules released from the gut microbiome can directly bind genomic DNA and act as transcriptional coregulators by recruiting transcription factors. These findings further unveil a molecular mechanism that connects gut metabolism to gene expression in the brain with implications for disease development.


Microbiology of Eye Infections at the Massachusetts Eye and Ear: An 8-Year Retrospective Review Combined With Genomic Epidemiology.
Ocular bacterial infections are important causes of morbidity and vision loss. Early antimicrobial therapy is necessary to save vision, but their efficacy is increasingly compromised by antimicrobial resistance (AMR). We assessed the etiology of ocular bacterial infections seen at Massachusetts Eye and Ear and investigated the molecular epidemiology and AMR profiles of contemporary isolates. Laboratory investigation. We used a combination of phenotypic tests and genome sequencing to identify the predominant lineages of leading ocular pathogens and their AMR profiles. A total of 1601 isolates were collected from 2014 to 2021, with Staphylococcus aureus (n = 621), coagulase-negative staphylococci (CoNS) (n = 234), Pseudomonas aeruginosa (n = 213), Enterobacteriaceae (n = 167), and Streptococcus pneumoniae (n = 95) being the most common. Resistance was high among staphylococci, with methicillin resistance (MR) detected in 28% of S aureus and 39.8% of CoNS isolates. Multidrug resistance (MDR) was frequent among MR staphylococci (MRSA 60%, MRCoNS 76.1%). The population of S aureus isolates consisted mainly of 2 clonal complexes (CCs): CC8 (26.1%) and CC5 (24.1%). CC5 strains carried a variety of AMR markers, resulting in high levels of resistance to first-line therapies. Similarly, the population of ocular Staphylococcus epidermidis was homogenous with most belonging to CC2 (85%), which were commonly MDR (48%). Conversely, ocular S pneumoniae, P aeruginosa, and Enterobacteriaceae were often susceptible to first-line therapies and grouped into highly diverse genetic populations. Our data showed that ocular bacterial infections in our patient population are disproportionately caused by strains that are resistant to clinically relevant antibiotics and are associated with major epidemic genotypes with both community and hospital associations.


Plasma acetate levels during hemodialysis.
Before dialysis, acetate levels in hemodialyzed patients (0.27--1.1 mmol/1) were more dispersed than in normal subjects (0.20--0.65 mmol/l) and the mean value of plasma acetate was slightly higher (0.52 mmol/l versus 0.31 mmol/l). Though dialysis conditions were almost identical, the acetate kinetics during hemodialysis were very different: in most subjects, plasma acetate concentrations reached a "plateau" (mean value 5.6 mmol/l) whereas in others a continuous rise was observed, suggesting that with patients having chronic renal failure there were important individual or occasional differences in the ability to metabolize acetate. The acetate loads per minute (or mass transfers) were calculated from the blood compartment with plasma values (plasma flow and concentrations), rather than from the dialysate and using the combined calculations (plasma and whole blood values). The results ranged between 2.4 and 4.1 mmol/min. A very important and rapid fall in arterial acetate concentrations occurs in the first 20 min after the end of the dialysis and proves the rapid turnover of the acetate in man.


Calcineurin antagonists in vulvar lichen sclerosus.
Lichen sclerosus et atrophicus is a chronic inflammatory disorder that mainly affects girls of premenarchial age and women in their fifties. Besides the anogenital region, lichen sclerosus (LS) may also affect extragenital or mucosal areas. Symptoms include soreness and pruritus, but other less common symptoms are not rare. An increased activity of fibroblasts causes increased sclerosis of the affected skin. Latest studies have identified LS as a chronic inflammatory dermatosis. Auto-antibodies against the extracellular membrane protein-1 are present in up to 80% of the patients. Moreover, in the widely accepted therapy with potent corticosteroids promising results have been presented using calcineurin antagonists in the treatment of LS. An interdisciplinary management and a continued care of patients with LS will improve the clinical manifestations and quality of life.


Long-term outcomes of modified glued versus flanged intrascleral haptic fixation techniques for secondary intraocular lenses.
To report the long-term refractive outcomes and complications of two scleral fixation techniques for secondary intraocular lenses (IOL). Consecutive patients who underwent secondary IOL insertion at a tertiary care academic hospital using either modified glued ("glued") or flanged intrascleral haptic fixation (FISHF) techniques with over 12 months of follow-up were retrospectively reviewed. Pre- and postoperative corrected distance visual acuity (CDVA), postoperative complications, and refractive surprises were reported. Thirty-eight patients underwent "glued" fixation and 22 underwent FISHF, with mean follow-up times of 3.1 ± 0.5 and 2.0 ± 1.2 years, respectively. Aphakia secondary to trauma was the main surgical indication. MA50BM or MA60AC IOLs (Alcon Laboratories Inc., Fort Worth, TX) were implanted in 92% of "glued" patients, while CT Lucia 602 IOLs (Carl Zeiss Meditec Inc., Dublin, CA) were used in 96% of FISHF patients. Postoperative spherical equivalent significantly improved compared to preoperative values (p < 0.001). No significant difference in CDVA was seen between the two techniques. FISHF resulted in mean hyperopic surprises of + 0.81D and + 0.69D using the Holladay 2 and Barrett Universal II formulae, respectively, which was significantly greater than the "glued" patients. A higher rate of IOL dislocation was seen in the "glued" cohort (13%) compared to FISHF (0%). Retrospective long-term outcomes of patients with complex ocular comorbidities undergoing a modified "glued" technique demonstrated a higher rate of IOL dislocation but more predictable refractive outcomes compared to the FISHF technique. The FISHF technique resulted in a significant hyperopic shift using fourth-generation IOL calculators.


Understanding the meaning of social well-being at the end of life.
To advance understanding of the social well-being domain, a dimension of quality of life, from the perspective of dying individuals. Qualitative, hermeneutic, and phenomenologic. Private residences in a community setting. 8 terminally ill adult patients with cancer, aged 35-75, enrolled in hospice care. In-depth, semistructured, tape-recorded, and transcribed interviews were analyzed using the Giorgi method. Social well-being and quality of life at the end of life. Six themes emerged that described the meaning of close personal relationships at the end of life: meaning of relationships with family, friends, and coworkers; meaning of relationships with God or a higher power; loss and gains of role function; love; gratitude; and lessons on living. Patients who were terminally ill with advanced cancer expressed the importance of close personal relationships at the end of life and the need to communicate their importance through love and gratitude. All participants believed that personal relationships were strengthened by the end-of-life experience. Nurses can support terminally ill patients by understanding the importance of social relationships at the end of life. The relationships may be enhanced when nurses raise patients' conscious awareness of the relationships and encourage them to express their importance.


Optic nerve head drusen and visual field loss in normotensive and hypertensive eyes.
To compare visual field loss (VFL) in eyes with optic nerve head drusen (ONHD) with or without ocular hypertension (OHT). The records of all patients aged 45 years or older with a diagnosis of ONHD at 2 centers were reviewed. OHT was defined as intraocular pressure >or=22 mm Hg. We categorized ONHD into 3 grades based on visibility on disc photographs. We identified 22 eyes (13 patients) with both ONHD and OHT and 81 normotensive eyes (47 patients) with ONHD. VFL was present in 20/22 (90.9%) of hypertensive eyes compared with 54/81 (66.7%) of normotensive eyes (P=0.03, Fisher exact test). Drusen grade III and OHT were both independently and significantly associated with greater incidence of VFL (logistic regression analysis). VFL occurs more frequently in eyes with ONHD that also have OHT. Eyes with grade III ONHD are at increased risk for VFL compared to eyes with grade I drusen with the same intraocular pressure status. Patients with OHT and ONHD should undergo close surveillance for disease progression and be treated appropriately to prevent additional VFL.


Cellular responses to bacterial lipopolysaccharide: LPS facilitates priming of antigen-reactive T cells.
The effect of bacterial lipopolysaccharide (LPS) on the capacity of mice to mount a specific T-cell response to a protein antigen was examined. Inoculation of mice with LPS and ovalbumin (OA) resulted in enhancement of the T-cell proliferative response to OA. This enhancement was manifested in vitro by an increase in magnitude and by a more rapid appearance of the response after challenge with OA. This enhancement was also shown because the latent periods for the antigen-specific responses were reduced to 3 days after inoculation with antigen plus LPS, as compared with 5 days after inoculation with antigen alone. Various mouse strains, including the C3H/HeJ and C57BL/10ScN strains, responded to the adjuvant action of LPS at the T-cell level. Results suggest that LPS exerts this adjuvant effect by facilitating clonal expansion of antigen-reactive T cells during priming.


Colorectal cancer, comorbidity, and risk of venous thromboembolism: assessment of biological interactions in a Danish nationwide cohort.
Venous thromboembolism (VTE) is a major source of morbidity and mortality in cancer patients. Incident colorectal cancer (CRC) and comorbidity both predict VTE, but potential synergy between these factors has not been explored. Danish nationwide cohort study of CRC cases diagnosed in 1995-2010 and a matched general population reference cohort of subjects without CRC who matched cases on age, sex, and comorbidities. We calculated the Charlson Comorbidity Index using diagnoses recorded in the Danish National Patient Registry. We calculated standardised incidence rates (SIRs) and interaction contrasts (IC) to measure additive interaction between comorbidity and CRC status with respect to 5-year VTE incidence. Among 56 189 CRC patients, 1372 VTE cases were diagnosed over 145 211 person-years (SIR=9.5 cases per 1000 person-years). Among 271 670 reference subjects, 2867 VTE cases were diagnosed over 1 068 860 person-years (SIR=2.8 cases per 1000 person-years). CRC and comorbidity were positively and independently associated with VTE, but there was no evidence for biological interaction between these factors (e.g., comparing the 'severe comorbidity' stratum with the 'no comorbidity' stratum, IC=0.8, 95% CI: -3.3, 4.8). There is neither a deficit nor a surplus of VTE cases among patients with both comorbidity and CRC, compared with rates expected from these risk factors in isolation.


Contrast advanced dynamic flow imaging and contrast pulse subtraction imaging: Preliminary results in hepatic tumors.
To investigate the usefulness of contrast advanced dynamic flow imaging and contrast pulse subtraction imaging in the intranodular hemodynamics of hepatic tumors. Ten patients underwent contrast advanced dynamic flow imaging and contrast pulse subtraction imaging using Levovist(®), a microbubble contrast agent. Fourteen hepatic tumor nodules were studied: 9 were hepatocellular carcinoma, 1 metastasis, 1 hemangioma, 1 adenomatous hyperplasia, and 2 metastatic lymph nodes of hepatocellular carcinoma. Real-time scanning of contrast advanced dynamic flow imaging and intermittent interval-delay scanning of contrast pulse subtraction imaging were carried out in the early arterial phase, the late vascular phase, and the postvascular phase. The results obtained from contrast advanced dynamic flow imaging and contrast pulse subtraction imaging were compared with those obtained by precontrast power Doppler imaging and three-phase dynamic CT, respectively. The rate of detection of intranodular vascularity by contrast advanced dynamic flow imaging (93%) or contrast pulse subtraction imaging (93%) was significantly higher than that of precontrast power Doppler imaging (29%) and was as high as that of dynamic CT. Characteristic intranodular hemodynamics were detected in hepatocellular carcinoma, metastasis, hemangioma, and adenomatous hyperplasia with typical appearance of an intranodular blood vessel image in the early arterial phase, a parenchymal stain image in the late vascular phase, and a perfusion defect image in the post-vascular phase. Contrast advanced dynamic flow imaging and contrast pulse subtraction imaging clearly show the intranodular hemodynamics in hepatic tumors.