Role of MicroRNAs in acceleration of vascular endothelial senescence.
Many factors are involved in cellular aging, and senescence induction requires complex regulation of various signaling networks and processes. Specifically, in the area of aging-related vascular cognitive impairment, laboratory-based findings have not yet yielded agents of practical use for clinical settings. One possible reason is that the physiologic elements of aging have been insufficiently considered. We sought to establish techniques to better model cellular aging using modulation of microRNAs, aiming to identify key microRNAs capable of fine-tuning aging-associated genes, and thereby regulating the senescence of vascular endothelial cells. We utilized expression microRNA arrays to evaluate control and senescent vascular endothelial cells in order to identify testable candidates. Bioinformatic analysis was used to select key microRNAs. These candidates were then modulated in vitro using microRNA mimics and inhibitors in endothelial cells, and senescence-associated gene expression patterns were evaluated by qPCR. Seventeen microRNAs were found to be significantly increased more than 2-fold in senescent cells. Of those, bioinformatic analysis concluded that miR-181a-5p, miR-30a-5p, miR-30a-3p, miR-100-5p, miR-21-5p, and miR-382-5p were likely associated with regulation of cellular senescence. We evaluated the potential targets of these six microRNAs by comparing them with cell-cycling and apoptosis-related genes from published mRNA transcriptional array data from aged tissues, and found that miR-181a-5p, miR-30a-5p and miR-30a-3p were enriched in overlapping targets compared with the other candidates. Modulation of these microRNAs in vascular endothelial cells revealed that over-expression of miR-30a-5p, and inhibition of both miR-30a-3p and miR-181a-5p, induced senescence. miR-181a-5p, miR-30a-5p and miR-30a-3p likely contribute to aging-associated vascular endothelial cell senescence.


Use of the bispectral index during the early postresuscitative phase after out-of-hospital cardiac arrest.
Non-invasive and real-time measures of neurological status after cardiac arrest are needed to be able to make an early determination of the postresuscitative outcome. We investigated whether the bispectral index (BIS) predicts the postresuscitative outcome in 10 patients with out-of-hospital cardiac arrest. We measured the BIS after return of spontaneous circulation (ROSC) in the emergency room and on admission to the intensive care unit (ICU). We determined the Glasgow Coma Scale (GCS) on admission to the emergency room and the ICU and the Glasgow Outcome Scale (GOS) on discharge from the ICU. The BIS increased after about 30 min of ROSC or reached a plateau in patients rated as achieving a good recovery or moderate disability, but it did not increase to >80 in patients rated as being in a permanent vegetative state/dead. The GCS on admission to the ICU was the same as that on admission to the emergency room. The BIS values were significantly lower in the nonsurviving group than in the surviving group. There was a positive correlation between the BIS on admission to the ICU and the GOS on discharge from the ICU. The BIS can thus be used to predict the postresuscitative outcome of patients with out-of-hospital cardiac arrest.


Direct observation of lithium-ion transport under an electrical field in LixCoO2 nanograins.
The past decades have witnessed the development of many technologies based on nanoionics, especially lithium-ion batteries (LIBs). Now there is an urgent need for developing LIBs with good high-rate capability and high power. LIBs with nanostructured electrodes show great potentials for achieving such goals. However, the nature of Li-ion transport behaviors within the nanostructured electrodes is not well clarified yet. Here, Li-ion transport behaviors in Li(x)CoO(2) nanograins are investigated by employing conductive atomic force microscopy (C-AFM) technique to study the local Li-ion diffusion induced conductance change behaviors with a spatial resolution of ~10 nm. It is found that grain boundary has a low Li-ion diffusion energy barrier and provides a fast Li-ion diffusion pathway, which is also confirmed by our first principles calculation. This information provides important guidelines for designing high performance LIBs from a point view of optimizing the electrode material microstructures and the development of nanoionics.


The landscape of plant genomics after 20 years.
Many letters of the plant genetic code have been read since the first plant genome was published in 2000 for Arabidopsis. In a recent paper, Marks et al. examined 798 plant genomes and provide a current view of plant genomics in terms of the quality of the assemblies, coupled with their taxonomical and geographical distribution.


Dural arteriovenous malformation associated with subdural and intracerebral hematoma: a CT scan and angiographic correlation.
Computed tomography of a case of hemorrhage from a dural arteriovenous malformation depicts an occipital varix with dilated venous channels, an intracerebral hematoma, a subdural hematoma and a subfacial hernation. The angiographic and surgical findings are described.


Spatiotemporal mutualistic model of mistletoes and birds.
A mathematical model which incorporates the spatial dispersal and interaction dynamics of mistletoes and birds is derived and studied to gain insights of the spatial heterogeneity in abundance of mistletoes. Fickian diffusion and chemotaxis are used to model the random movement of birds and the aggregation of birds due to the attraction of mistletoes, respectively. The spread of mistletoes by birds is expressed by a dispersal operator, which is typically a convolution integral with a dispersal kernel. Two different types of kernel functions are used to study the model, one is a Dirac delta function which reflects the special case that the spread behavior is local, and the other one is a general non-negative symmetric function which describes the nonlocal spread of mistletoes. When the kernel function is taken as the Dirac delta function, the threshold condition for the existence of mistletoes is given and explored in terms of parameters. For the general non-negative symmetric kernel case, we prove the existence and stability of spatially nonhomogeneous equilibria. Numerical simulations are conducted by taking specific forms of kernel functions. Our study shows that the spatial heterogeneous patterns of mistletoes are related to the specific dispersal pattern of birds which carry mistletoe seeds.


DNA methylation-mediated silencing of FLT1 in parthenogenetic porcine placentas.
Studies show that perturbed expression of vascular endothelial growth factor (VEGF) family genes is related to abnormal development of parthenogenetic (PA) placenta. In this study, the methylation status of VEGF family genes were compared between PA and normal placentas using bisulfite sequencing PCR (BSP). Results showed no significant difference in the methylation of VEGF-A differentially methylated region (DMR), placental growth factor (PIGF) DMR, and kinase insert domain receptor (KDR) DMR, whereas FMS-like tyrosine kinase 1 (FLT1) DMR was hypermethylated in PA placentas. These results suggested that abnormal methylation of FLT1 DMR might trigger the developmental failure of porcine PA placentas.


[Development of a cooperative autopsy network of pathology, neuropathology and forensic medicine].
Autopsies are an important tool for understanding novel diseases, including COVID-19. The German Registry of COVID-19 Autopsies (DeRegCOVID) was established and launched in April 2020. DeRegCOVID acts as the electronic backbone of the German Network for Autopsies in Pandemics (DEFEAT PANDEMIcs), which started in September 2020. The results of DeRegCOVID and DEFEAT PANDEMIcs are characterized by an unprecedented collaboration of more than 35 university and non-university autopsy centers linking pathological, neuropathological, and forensic medicine institutes. DeRegCOVID has evolved, adapted to new challenges, and currently contains the largest international autopsy dataset. After only a short period of operation, more than 80 publications have been produced, which have contributed to the understanding of the pathogenesis of COVID-19, e.g., through the discovery of thromboembolic events, multiorgan tropism, and NeuroCovid-19. The autopsy centers have carried out extensive educational work and, beyond the scientific gain in knowledge, have explained to politicians and the general public the essential role of autopsies in pandemic management. To further develop autopsy-driven research, a continuation of DEFEAT PANDEMIcs was conceived, the National Autopsy Network (NATON). The registry and network, in which all interested centers can participate, have demonstrated the value of networked medical research and the high value of autopsy for medicine.


Behavioral symptoms in vascular cognitive impairment and vascular dementia.
Noncognitive or behavioral and psychological symptoms (BPSD) are common in vascular dementia. Many occur with the same frequency as in Alzheimer's disease, though depression, emotional lability, and apathy may be more common and psychosis less so. There is a particularly strong relationship between cerebrovascular disease and depression.


The stress of being a poor child in America.
This article explores the human ecology of child poverty. It focuses on the psychologic meanings of poverty in American society. Issues of shame linked to economic inequality rather than limited resource possession are at the core of clinical issues associated with poverty.


The role of acetylation sites in the regulation of p53 activity.
As a "genomic guardian", p53 mainly functions as a transcription factor that regulates downstream targets responsible for cell fate control, and the activity of p53 is tightly regulated by a complex network that include an abundance of post-translational modifications. Notably, acetylation of p53 at many positions has been demonstrated to play a major role in accurate p53 regulation and cell fate determination. However, no evidence has been provided to compare the effect of acetylation at different sites on p53 regulation. Here, we constructed six acetylation-defective p53 mutants that lysine was substituted by arginine at residues 120, 164, 305, 320, 370/372/373 or 381/382/386, respectively, and determined their effects on p53 activity systematically. Our results showed that all six mutants exhibited diminished transactivation ability and selective regulation of target genes expression through distinct mechanisms. Specifically, lysine 370/372/373 and 381/382/386 mutations decreased p53 stability, and lysine 305 mutation reduced p53 phosphorylation level at serine 15, while lysine 120 and 164 mutations decreased p53 acetylation level at lysine 382. Collectively, these data indicate that acetylation of p53 at different sites has diverse regulatory effects on p53 transcriptional activity through different mechanisms.


Extensive characterization of aerosol optical properties and chemical component concentrations: Application of the GRASP/Component approach to long-term AERONET measurements.
A recently developed GRASP/Component approach (GRASP: Generalized Retrieval of Atmosphere and Surface Properties) was applied to AERONET (Aeronet Robotic Network) sun photometer measurements in this study. Unlike traditional aerosol component retrieval, this approach allows the inference of some information about aerosol composition directly from measured radiance, rather than indirectly through the inversion of optical parameters, and has been integrated into the GRASP algorithm. The newly developed GRASP/Component approach was applied to 13 AERONET sites for different aerosol types under the assumption of aerosol internal mixing rules to analyze the characteristics of aerosol components and their distribution patterns. The results indicate that the retrievals can characterize well the spatial and temporal variability of the component concentration for different aerosol types. A reasonable agreement between GRASP BC retrievals and MERRA-2 BC products is found for all different aerosol types. In addition, the relationships between aerosol component content and aerosol optical parameters such as aerosol optical depth (AOD), fine-mode fraction (FMF), absorption Ångström exponent (AAE), scattering Ångström exponent (SAE), and single scattering albedo (SSA) are also analyzed for indirect verifying the reliability of the component retrieval. It was demonstrated the GRASP/Component optical retrievals are in good agreement with AERONET standard products [e.g., correlation coefficient (R) of 0.93-1.0 for AOD, fine-mode AOD (AODF), coarse-mode AOD (AODC) and Ångström exponent (AE); R = ~ 0.8 for absorption AOD (AAOD) and SSA; RMSE (root mean square error) < 0.03 for AOD, AODF, AODC, AAOD and SSA]. Thus, it is demonstrated the GRASP/Component approach can provide aerosol optical products with comparable accuracy as the AERONET standard products from the ground-based sun photometer measurements as well as some additional important inside on aerosol composition.


Selection methodology with scoring system: application to Mexican plants producing podophyllotoxin related lignans.
As most anticancer drugs are derived from natural sources, the screening of local medicinal flora should be considered a primary step in the search for new sources for antineoplastic agents. In Mexico, more than 6000 medicinal plant species are used for the treatment of various diseases, including cancer. A multifactorial plant selection method, employing various criteria was designed and applied in order to select alternative sources of podophyllotoxin lignan analogues. For each criterion (chemotaxonomy, traditional medical uses and published scientific data), an arbitrary score system was ascribed to the species and the sum of these enabled us to compare potential candidates. The resulting selected plants were tested for cytotoxic activity and the compounds responsible for this activity were evaluated by liquid chromatography-mass spectroscopy (LC-MS). Around 50 species from the Mexican flora were initially considered. From these, six species were selected by referring to the results from the scoring system and these were then collected. Three extracts were evaluated as being highly cytotoxic against three different cancer cell lines. Finally, podophyllotoxin-like lignans could be identified by observing the fragmentation pattern on mass spectra, obtained from the LC-MS in two species: Linum scabrellum and Hyptis suaveolens.


Exploring the driving factors of haze events in Beijing during Chinese New Year holidays in 2020 and 2021 under the influence of COVID-19 pandemic.
Unexpected outbreak of the 2019 novel coronavirus (COVID-19) has profoundly altered the way of human life and production activity, which posed visible impacts on PM2.5 and its chemical species. The abruptly emergency reduction in human activities provided an opportunity to explore the synergetic impacts of multi-factors on shaping PM2.5 pollution. Here, we conducted two comprehensive observation measurements of PM2.5 and its chemical species from 1 January to 16 February in Beijing 2020 and the same lunar date in 2021, to investigate temporal variations and reveal the driving factors of haze before and after Chinese New Year (CNY). Results show that mean PM2.5 concentrations during the whole observation were 63.83 and 66.86 μg/m3 in 2020 and 2021, respectively. Higher secondary inorganic species were observed after CNY, and K+, Cl- showed three prominent peaks which associated closely with fireworks burnings from suburb Beijing and surroundings, verifying that they could be used as two representative tracers of fireworks. Further, we explored the impacts of meteorological conditions, regional transportation as well as chemical reactions on PM2.5. We found that unfavorable meteorological conditions accounted for 11.0 % and 16.9 % of PM2.5 during CNY holidays in 2020 and 2021, respectively. Regional transport from southwest and southeast (south) played an important role on PM2.5 during the two observation periods. Higher ratio of NO3-/SO42- were observed under high OX and low RH conditions, suggesting the major pathway of NO3- and SO42- formation could be photochemical process and aqueous-phase reaction. Additionally, nocturnal chemistry facilitated the formation of secondary components of both inorganic and organic. This study promotes understandings of PM2.5 pollution in winter under the influence of COVID-19 pandemic and provides a well reference for haze and PM2.5 control in future.


How important is the butyrylcholinesterase level for cesarean section?
Butyrylcholinesterase (BChE), commonly known as pseudocholinesterase or non-neural cholinesterase, hydrolyzes neuromuscular blocker agents containing choline esters such as succinylcholine that is widely used in rapid sequence induction (RSI) for general anesthesia. The aim of this study is to compare plasma BChE levels and investigate the affects and relationship of succinylcholine on BChE levels in preeclamptic, gestational diabetic and healthy pregnants. We designed a prospective, controlled, pilot single-center study. Thirty (n=30) pregnant women who were scheduled for cesarean section under general anesthesia (refusal of regional anesthesia) with RSI involved. Group 1 included ten (n=10) preeclamptic pregnancies, Group 2 included ten (n=10) gestational diabetic (GD) pregnancies and Group 3 included ten (n=10) healthy pregnancies. BChE levels of all patients were measured prior to the initiation of cesarean section. Train-of-four recovery of 90% (TOF T1) was used to monitor the degree of neuromuscular block beginning from the administration of succinylcholine. No statistically significant difference was found between the groups comparing BChE levels and the duration between tracheal intubation and formation of TOF T1 (p>0.05). As similar results were gathered from normal and high-risk pregnancies (preeclamptic pregnancy or gestational diabetic pregnancy) who underwent cesarean section under general anesthesia, we believe that succinylcholine is still neuromuscular agent of choice in cesarean section.


[ERAS, from concept to care].
Enhanced recovery after surgery (ERAS) aims at reducing the length of hospital stays and complications. Everyone has a role to play - healthcare professionals, medical secretaries, administrative staff and patients. A coordinated treatment pathway must be ensured and changes in practices must be accepted.


Angioplasty for symptomatic intracranial stenosis: clinical outcome.
Medical treatment of symptomatic intracranial stenosis carries a high risk of stroke. This study was done to evaluate the clinical and angiographic outcomes after intracranial angioplasty for this disease. A total of 120 patients with 124 intracranial stenoses were treated by primary angioplasty. All patients had neurologic symptoms (stroke or transient ischemic attack) attributable to intracranial stenoses > or =50%. Angiograms were evaluated before and after angioplasty for the degree of stenosis. Pretreatment stenoses varied from 50% to 95% (mean 82.2+/-10.2). Post-treatment stenoses varied from 0% to 90% (mean 36.0+/-20.1). There were 3 strokes and 4 deaths (all neurological) within 30 days of the procedure, giving a combined periprocedural stroke and death rate of 5.8%. A total of 116 patients (96.7%) were available for a mean follow-up time of 42.3 months. There were 6 patients who had a stroke in the territory of treatment and 5 additional patients with stroke in other territories. Ten deaths occurred during the follow-up period, none of which were neurological. Including the periprocedural stroke and deaths, this yielded an annual stroke rate of 3.2% in the territory of treatment and a 4.4% annual rate for all strokes. Intracranial angioplasty can be performed with a high degree of technical success and a low risk of complications. Long-term clinical follow-up of intracranial angioplasty patients demonstrates a risk of future strokes that compares favorably to patients receiving medical therapy.


Cognitive-affective processes and suicidality in response to repetitive transcranial magnetic stimulation for treatment resistant depression.
Repetitive transcranial magnetic stimulation (rTMS) can elicit 45-55 % response rates and may alleviate suicidality symptoms in treatment resistant depression (TRD). Blunted anticipatory reward sensitivity and negatively biased self-referential processing may predict trajectories of depressive and suicidality symptoms in rTMS for TRD and be modulated during treatment. Fifty-five individuals with TRD received four weeks of low-frequency rTMS applied to the right dorsolateral prefrontal cortex (LFR-rTMS) and were followed until 17 weeks post-baseline. Participants completed behavioral measures of anticipatory reward sensitivity and self-referential processing at baseline and five weeks post-baseline (approximately one-week post-treatment). We examined whether baseline anticipatory reward sensitivity and self-referential processing predicted trajectories of depressive and suicidality symptoms from baseline to follow-up and whether these cognitive-affective variables showed change from baseline to week five. Anticipatory reward sensitivity and negative self-referential encoding at baseline were associated with higher overall depressive symptoms and suicidality from baseline to 17 weeks post-baseline. At week five, participants self-attributed a higher number of positive traits and a lower number of negative traits and had a lesser tendency to remember negative relative to positive traits they had self-attributed, compared to baseline. The specificity of these results to LFR-rTMS is unknown in the absence of a comparison group, and our relatively small sample size precluded the interpretation of null results. Baseline blunted anticipatory reward sensitivity and negative biases in self-referential processing may be risk factors for higher depressive symptoms and suicidality during and after LFR-rTMS, and LFR-rTMS may modulate self-referential processing.


Dual camera snapshot high-resolution-hyperspectral imaging system with parallel joint optimization via physics-informed learning.
The hardware architecture of the coded aperture snapshot spectral imaging (CASSI) system is based on a coded mask design, resulting in a poor spatial resolution of the system. Therefore, we consider the use of a physical model of optical imaging and a jointly optimized mathematical model to design a self-supervised framework to solve the high-resolution-hyperspectral imaging problem. In this paper, we design a parallel joint optimization architecture based on a two-camera system. This framework combines the physical model of optical system and a joint optimization mathematical model, which takes full advantage of the spatial detail information provided by the color camera. The system has a strong online self-learning capability for high-resolution-hyperspectral image reconstruction, and gets rid of the dependence of supervised learning neural network methods on training data sets.


Substrate specificity of thePenicillium lilacinum enzyme lytic to the cell wall ofRhodotorula glutinis and the structure of theRhodotorula cell wall glucomannan.
The lytic enzyme active on cell walls ofRhodotorula, which was produced byPenicillium lilacinum ATCC 36010, decomposed an extracellular mannan fromRhodotorula glutinis IFO 0695 and was confined to the β-1,3-mannoside bond on the reducing side of the β-1,4-linkedD-mannopyranose. Based on these results, the structure of the glucomannan, which was a major component ofRhodotorula cell walls, was proposed.


The 3-iodothyronamine (T1AM) and the 3-iodothyroacetic acid (TA1) indicate a novel connection with the histamine system for neuroprotection.
The 3-iodothyronamine (T1AM) and 3-iodothryoacetic acid (TA1), are endogenous occurring compounds structurally related with thyroid hormones (THs, the pro-hormone T4 and the active hormone T3) initially proposed as possible mediators of the rapid effects of T3. However, after years from their identification, the physio-pathological meaning of T1AM and TA1 tissue levels remains an unsolved issue while pharmacological evidence indicates both compounds promote in rodents central and peripheral effects with mechanisms which remain mostly elusive. Pharmacodynamics of T1AM includes the recognition of G-coupled receptors, ion channels but also biotransformation into an active metabolite, i.e. the TA1. Furthermore, long term T1AM treatment associates with post-translational modifications of cell proteins. Such array of signaling may represent an added value, rather than a limit, equipping T1AM to play different functions depending on local expression of targets and enzymes involved in its biotransformation. Up to date, no information regarding TA1 mechanistic is available. We here review some of the main findings describing effects of T1AM (and TA1) which suggest these compounds interplay with the histaminergic system. These data reveal T1AM and TA1 are part of a network of signals involved in neuronal plasticity including neuroprotection and suggest T1AM and TA1 as lead compounds for a novel class of atypical psychoactive drugs.


Neutrophil migration into indomethacin induced rat small intestinal injury is CD11a/CD18 and CD11b/CD18 co-dependent.
Neutrophils may exacerbate intestinal inflammatory diseases through secretion of proteolytic enzymes and reactive oxygen and nitrogen intermediates. To define the mechanisms involved in neutrophil infiltration into the non-steroidal anti-inflammatory disease inflamed intestine to develop strategies to regulate this process. The small intestinal epithelium of (15 mg/kg) indomethacin treated rats was examined for cytokine mRNA. The kinetics of neutrophil accumulation into the gastrointestinal tract (including lumen contents) of inflamed rats was determined using radiolabelled (111In) neutrophils injected intravenously followed by a three hour migration period. To determine which adhesion molecules were critical for migration, rats were also injected with function blocking monoclonal antibodies to the beta2 (CD11/CD18) integrins. Interleukin 1beta, interleukin 1 receptor II, tumour necrosis factor alpha, and monocyte inflammatory peptide 2 but not monocyte chemoattractant protein 1 mRNA were detected in the epithelium within hours of indomethacin injection. Neutrophils were detectable in the small intestine and intestinal lumen by six hours and continued to accumulate until 48 hours post indomethacin injection. Neutrophil accumulation in the intestine was essentially blocked by anti-CD18, and partially blocked by either anti-CD11a or CD11b antibody treatment. Migration into the intestinal lumen was reduced by anti-CD11b. The small intestinal epithelium acts as one source of cytokines with properties important in the recruitment of neutrophils. In turn, neutrophil migration into the indomethacin inflamed small intestine is mediated by CD11a/CD18 and CD11b/CD18.


Development and validation of a risk prediction model for visual impairment in older adults.
This study aimed to determine the risk factors that affect visual impairment in older adults for developing and evaluating a visual impairment risk prediction model. In this hospital-based unmatched case-control design study, we enrolled 586 participants (411 in the training set and 175 in the internal test set) from the ophthalmology clinic and physical examination center of a teaching hospital in Liaoning Province, China, from June to December 2020. Visual impairment was defined as best-corrected visual acuity <6/18 (The WHO definition). Possible influencing factors of visual impairment were assessed, including demographic factors, socioeconomic factors, disease and medication factors, and lifestyle. A visual impairment risk prediction model was developed using binary logistic regression analysis. The area under the ROC curve (AUC) was used to evaluate the effectiveness of the proposed prediction model. Six independent influencing factors of visual impairment in older adults were identified: age, systolic blood pressure, physical activity scores, diabetes, self-reported ocular disease history, and education level. A visual impairment risk prediction model for older adults was developed, showing powerful predictive ability in the training set and internal test set with AUCs of 0.87 (95%CI 0.83-0.90) and 0.81 (95%CI 0.74-0.88), respectively. The risk prediction model for visual impairment in older adults had high predictive power. Identifying older adults at risk for developing visual impairment can help healthcare workers to adopt appropriate targeted programs for early education and intervention to prevent or delay visual impairment and prevent injuries due to visual impairment in older adults.


Association between Sleep Duration and Depression among the Elderly Population in China.
The objective of this study was to understand how sleep duration could affect depression among elderly in China. A total of 7103 individuals aged 60 and older were selected from China Health and Retirement Longitudinal Study. A generalized linear mixed-effects model was used to estimate the relationship between sleep duration and depression, and we performed stratified analyses by age: young-old elderly, old-old elderly and oldest-old elderly. Short sleep duration significantly incresased CES-D10 depression scores. In addition, the participants with middle sleep duration had higher CES-D10 scores compared to the participants with long sleep duration among young-old elderly, and we found that middle sleep duration was not significantly different from CES-D10 scores after adjustment for demographics, frequencies of activities and Chronic diseases. These findings suggested that there was a complex association between depression and sleep duration among elderly in China. Different from previous research results on the middle or normal sleep time of the elderly, the middle sleep duration maybe not optimal sleep duration in this study. Investigation of sleep extension to prevent depression may be warranted among the elderly.


Determination of aliphatic aldehydes as their thiazolidine derivatives in foods by gas chromatography with flame photometric detection.
A selective and sensitive gas chromatographic method for the determination of saturated and unsaturated aliphatic aldehydes in foods has been developed. After extraction of the sample with acetonitrile, aldehydes were converted into their thiazolidine derivatives by the reaction with cysteamine, and then measured by gas chromatography with flame photometric detection. The calibration curves for aliphatic aldehydes in the range 20-2500 ng were linear and the detection limits at a signal-to-noise ratio of 3 were ca. 4-100 pg injected. Aliphatic aldehydes in foods could be selectively determined by this method without any interference from coexisting substances. Overall recoveries of aldehydes added to food samples were 82-111%. Analytical results for the determination of aliphatic aldehydes in various food samples are presented.


Direct recovery of infectious pestivirus from a full-length RT-PCR amplicon.
This study describes the use of a novel and rapid long reverse transcription (RT)-PCR for the generation of infectious full-length cDNA of pestiviruses. To produce rescued viruses, full-length RT-PCR amplicons of 12.3 kb, including a T7-promotor, were transcribed directly in vitro, and the resulting RNA transcripts were electroporated into ovine cells. Infectious virus was obtained after one cell culture passage. The rescued viruses had a phenotype similar to the parental Border Disease virus strain. Therefore, direct generation of infectious pestiviruses from full-length RT-PCR cDNA products could be a valuable instrument for virus rescue, conservation and further characterization.


Ultrastructure of the heart muscle cells of the cuttlefish Rossia macrosoma (Delle Chiaje) (Mollusca: Cephalopoda).
The muscle cells of the ventricle, the branchial heart and the branchial heart appendages of Rossia macrosoma (Delle Chiaje) are studied. The ventricle myocardium has three muscle layers, while the other two organs exhibited a loose arrangement of muscle cells. The muscle cells of the ventricle, the branchial heart and the branchial heart appendages are similar in structure. The nuclei are surrounded by myofibrils. In the myofibrils A-, I- and discontinuous Z-bands are seen. The diameters of the thick filaments are 300--400A, their length varies from 1.7 to 3.9 mu. Thin filaments have a diameter of approximately 85A. The ratio between thick and thin filaments is roughly 1 to 11. The SR runs mostly as a longitudinal network within the myofibrils. A few short T-tubules are observed in the Z-regions. Peripheral and internal couplings exist. The latter are few in number. Intercalated discs are small and rarely observed. They have been found in all three organs. A difference in the function of these organs is not reflected in the ultrastructure of the intercalated discs. These discs are often of the interdigitating type with interfibrillar junctions and unspecialized regions. Peripheral couplings are seen at the unspecialized regions. The intercalar surfaces of the muscle cells "shoulder off" into the lateral surface, and the transition between the two surfaces is not a sharp one. Attachment plaques are found scattered over the whole sarcolemma.


Modulation of radiation-induced oral mucositis by thalidomide : Preclinical studies.
Oral mucositis is a common, dose-limiting early side effect of radio(chemo)therapy for head-and-neck tumors. The epithelial radiation response is accompanied by changes in the inflammatory signaling cascades mediated by the transcription factor nuclear factor-kappa B (NF-κB). The present study was initiated to determine the effect of the NF-κB inhibitor thalidomide on the clinical manifestation of oral mucositis in the established mouse tongue model. Treatment protocols comprised single dose irradiation and daily fractionated irradiation (5 fractions of 3 Gy/week) over 1 (days 0-4) or 2 weeks (days 0-4, 7-11), alone or in combination with daily thalidomide application (100 mg/kg intraperitoneally) over varying time intervals. Fractionation protocols were terminated by graded local radiation doses (day 7/14) to generate full dose-effect curves. Tongue epithelial ulcerations, corresponding to confluent mucositis, served as the clinically relevant endpoint. Thalidomide application did not show a significant radioprotective potential when administered in combination with single dose irradiation. Thalidomide in combination with one week of fractionated irradiation significantly increased the isoeffective top-up doses. Similar results were observed during two weeks of fractionated irradiation in all but one experiment. Thalidomide treatment demonstrated a significant mucositis-ameliorating effect during fractionated irradiation, which is likely to result from NF-κB inhibition. However, further mechanistic studies are required to define the underlying mechanisms of the observed mucoprotective effect.


The pharmaceutics from the foreign empire: the molecular pharming of the prokaryotic staphylokinase in Arabidopsis thaliana plants.
Here, we present the application of microbiology and biotechnology for the production of recombinant pharmaceutical proteins in plant cells. To the best of our knowledge and belief it is one of few examples of the expression of the prokaryotic staphylokinase (SAK) in the eukaryotic system. Despite the tremendous progress made in the plant biotechnology, most of the heterologous proteins still accumulate to low concentrations in plant tissues. Therefore, the composition of expression cassettes to assure economically feasible level of protein production in plants remains crucial. The aim of our research was obtaining a high concentration of the bacterial anticoagulant factor-staphylokinase, in Arabidopsis thaliana seeds. The coding sequence of staphylokinase was placed under control of the β-phaseolin promoter and cloned between the signal sequence of the seed storage protein 2S2 and the carboxy-terminal KDEL signal sequence. The engineered binary vector pATAG-sak was introduced into Arabidopsis thaliana plants via Agrobacterium tumefaciens-mediated transformation. Analysis of the subsequent generations of Arabidopsis seeds revealed both presence of the sak and nptII transgenes, and the SAK protein. Moreover, a plasminogen activator activity of staphylokinase was observed in the protein extracts from seeds, while such a reaction was not observed in the leaf extracts showing seed-specific activity of the β-phaseolin promoter.


Predicting low birthweight and complicated labor in urban black women: a biopsychosocial perspective.
This study explored demographic, biomedical and psychosocial factors as predictors of two adverse pregnancy outcomes: intrapartum complications and low birthweight, in 140 urban black pregnant women. The intrapartum complication rate was 18%. A four factor equation (low family functioning, advanced maternal age, working during pregnancy, and short stature) predicted intrapartum complications (80% sensitivity, 67% specificity and 35% positive predictive value). The low birthweight rate was 14%. Four factors (low family functioning, stressful events, Quetelet's Index, and cigarette smoking) predicted low birthweight (65% sensitivity, 84% specificity and 42% positive predictive value). Family functioning, alone, predicted low birthweight with 65% sensitivity, 64% specificity and 31% positive predictive value. Family functioning, was the only predictor for both outcomes. Family functioning and other psychosocial risk factors may potentially improve identification of high risk pregnant urban black women.


Interaction between a medical group and a school of public health: a case study of a productive affiliation.
As schools of the health sciences come under increasing financial pressures and providers must cope with the increasing complexity of the health care system, mutually supportive arrangements may become more common and more important to both parties. Underlying such arrangements is the expectation that the schools of the health sciences may gain sources of support for professional education and access to training opportunities and that the providers may gain in operational capacity and access to specialized expertise. We have developed a collaborative relationship between a school of public health and a multispecialty group medical practice. Although in some respects an improbable combination, the relationship has yielded benefits and may be of interest to other institutions.


Competing risks in epidemiology: possibilities and pitfalls.
In studies of all-cause mortality, the fundamental epidemiological concepts of rate and risk are connected through a well-defined one-to-one relation. An important consequence of this relation is that regression models such as the proportional hazards model that are defined through the hazard (the rate) immediately dictate how the covariates relate to the survival function (the risk). This introductory paper reviews the concepts of rate and risk and their one-to-one relation in all-cause mortality studies and introduces the analogous concepts of rate and risk in the context of competing risks, the cause-specific hazard and the cause-specific cumulative incidence function. The key feature of competing risks is that the one-to-one correspondence between cause-specific hazard and cumulative incidence, between rate and risk, is lost. This fact has two important implications. First, the naïve Kaplan-Meier that takes the competing events as censored observations, is biased. Secondly, the way in which covariates are associated with the cause-specific hazards may not coincide with the way these covariates are associated with the cumulative incidence. An example with relapse and non-relapse mortality as competing risks in a stem cell transplantation study is used for illustration. The two implications of the loss of one-to-one correspondence between cause-specific hazard and cumulative incidence should be kept in mind when deciding on how to make inference in a competing risks situation.


Immobilization of Agrobacterium tumefaciensd-psicose 3-epimerase onto titanium dioxide for bioconversion of rare sugar.
d-Psicose (d-ribo-2-hexulose or d-allulose) is the Carbon-3 epimer of d-fructose sugar and considered as an unnatural (rare) sugar found in low amount in nature. It has about 70% of the relative sweetness but 0.3% of the energy of sucrose, which is suggested as the most suitable sucrose substitute for food additives. Enzymatic biosynthesis using ketose 3-epimerases is a necessary procedure for the production of d-Psicose from d-fructose. However, significant drawbacks in the application of ketose 3-epimerases at industrial scale observe lower thermal stability as well as bioconversion efficiency, reusability and recovery of the enzyme. We have attempted immobilization of ketose 3-epimerases from Agrobacterium tumefaciens (agtu) d-psicose 3-epimerase (DPEase) on titanium dioxide. Further, Scanning electron microscopy (SEM), inverted microscopy, Fourier transform infrared spectroscopy (FTIR) and UV-vis spectroscopy showed that the enzyme was successfully immobilized on the titanium dioxide (TiO2) surface. Titanium dioxide immobilized agtu-DPEase (TiO2-agtu-DPEase) shows pH optima at 6.0 and 60 °C as a higher working temperature. TiO2-agtu-DPEase showed a half-life of 180 min at 60 °C, which is higher as compared to Agrobacterium tumefaciens (agtu) DPEase (3.99 min at 50 °C). At equilibrium, 36:64 (D-psicose: d-fructose), the bioconversion efficiency was accounted for titanium dioxide immobilized DPEase, which is higher than the agtu-DPEase. Titanium dioxide immobilized DPEase showed bioconversion efficiency up to 9 cycles of reusability.


Molecular cloning, sequencing, and physiological characterization of the qox operon from Bacillus subtilis encoding the aa3-600 quinol oxidase.
Bacillus subtilis contains two aa3-type terminal oxidases (caa3-605 and aa3-600) catalyzing cytochrome c and quinol oxidation, respectively, with the concomitant reduction of O2 to H2O (Lauraeus, M., Haltia, T., Saraste, M., and Wikström, M. (1991) Eur. J. Biochem. 197, 699-705). Previous studies characterized only the structural genes of caa3-605 oxidase. We isolated the genes coding for the four subunits of a B. subtilis terminal oxidase from a genomic DNA library. These genes, named qoxA to qoxD, are organized in an operon. Examination of the deduced amino acid sequence of Qox subunits showed that this oxidase is structurally related to the large family of mitochondrial-type aa3 terminal oxidases. In particular, the amino acid sequences are very similar to those of subunits of Escherichia coli bo quinol oxidase and B. subtilis caa3-605 cytochrome c oxidase. We produced, by in vitro mutagenesis, a mutation in the qox operon. From the phenotype of the mutant strain devoid of Qox protein, the study of expression of the qox operon in different growth conditions, and the analysis of the deduced amino acid sequence of the subunits, we concluded that Qox protein and aa3-600 quinol oxidase are the same protein. Although several terminal oxidases are found in B. subtilis, Qox oxidase (aa3-600) is predominant during the vegetative growth and its absence leads to important alterations of the phenotype of B. subtilis.


Morphometric analyses of hominoid crania, probabilities of conspecificity and an approximation of a biological species constant.
Thackeray has previously explored the possibility of using a morphometric approach to quantify the "amount" of variation within species and to assess probabilities of conspecificity when two fossil specimens are compared, instead of "pigeon-holing" them into discrete species. In an attempt to obtain a statistical (probabilistic) definition of a species, Thackeray has recognized an approximation of a biological species constant (T=-1.61) based on the log-transformed standard error of the coefficient m (log sem) in regression analysis of cranial and other data from pairs of specimens of conspecific extant species, associated with regression equations of the form y=mx+c where m is the slope and c is the intercept, using measurements of any specimen A (x axis), and any specimen B of the same species (y axis). The log-transformed standard error of the co-efficient m (log sem) is a measure of the degree of similarity between pairs of specimens, and in this study shows central tendency around a mean value of -1.61 and standard deviation 0.10 for modern conspecific specimens. In this paper we focus attention on the need to take into account the range of difference in log sem values (Δlog sem or "delta log sem") obtained from comparisons when specimen A (x axis) is compared to B (y axis), and secondly when specimen A (y axis) is compared to B (x axis). Thackeray's approach can be refined to focus on high probabilities of conspecificity for pairs of specimens for which log sem is less than -1.61 and for which Δlog sem is less than 0.03. We appeal for the adoption of a concept here called "sigma taxonomy" (as opposed to "alpha taxonomy"), recognizing that boundaries between species are not always well defined.


Do patients with psoriasis are at higher risk for atherogenity? A case-control study.
Psoriasis is a chronic, inflammatory skin disease that is common in both adult and childhood. Patients with psoriasis are at significant risk for the development of many comorbid conditions, including cardiovascular diseases. We aimed to investigate the cardiovascular risk status and serum lipid parameters in patients with psoriasis and to determine the risk of cardiovascular disease by atherogenic indices obtained accordingly. This retrospective case-control study was conducted with a total of 142 individuals, 72 patients with psoriasis vulgaris and 70 healthy volunteers over the age of 18 who were admitted to the dermatology outpatient clinic. Demographic information and laboratory values were retrieved from the hospital database. Afterward, atherogenic indexes such as Atherogenic index of plasma (AIP), Castelli Risk Index I and II (CRI-I and II), and Atherogenic coefficient (AC) were calculated. There was a significant difference in lipid profile between the psoriasis patients and the control group. In patients with psoriasis, triglyceride level (140.09 ± 71.20 mg/dl vs. 116.10 ± 63.95, p = 0.037) was higher, while HDL level (44.34 ± 11.77 mg/dl vs. 50.31 ± 11.62, p = 0.003) was lower. Regarding atherogenic indices; AIP (0.10 ± 0.24 vs. -0.04 ± 0.27, p = 0.001), CRI-I (4.63 ± 1.40 vs. 3.94 ± 1.02, p = 0.001), CRI-II (2.98 ± 1.01 vs. 2.61 ± 0.82, p = 0.019) and AC (3.63 ± 1.40 vs.. 2.94 ± 1.02, p = 0.001) were significantly higher in patients with psoriasis. Our study shows that patients with psoriasis have higher pro-atherogenic lipid profile and atherogenic indexes at a high risk level. Patients with psoriasis have an increased risk of cardiovascular diseases.


The effect of glycemic control on Candida colonization of the tongue and the subgingival plaque in patients with type II diabetes and periodontitis.
Identify the relationship between the tongue and subgingival plaque Candida colonization, and its relationship to the quality of glycemic control (assessed by glycosylated hemoglobin) and other confounders, in type II diabetics who have periodontitis. Candida species were isolated from the tongue and subgingival plaque of the 2 deepest periodontal pockets from 78 patients, and were identified by RapID Yeast Plus System. Student's t test, χ(2) test or Fisher's exact test, analysis of variance, multivariate logistic regression analysis, and Spearman's correlation test were used. Candida species colonized 46 (59%) and 38 (48.7%) of the patients tongue and subgingival plaque, respectively. Subgingival Candida was more prevalent in females than males (P = .041). The quality of glycemic control correlated with the prevalence of subgingival Candida (P = .047) and the severity of gingival disease (P = .047). Poor glycemic control and female gender may be associated with increased subgingival Candida in patients with type II diabetes.


TRH raises cytosolic Ca2+ in human adenomatous lactotrophs.
The effect of TRH on cytosolic free calcium concentrations, [Ca2+]i, was evaluated on cell suspensions obtained from 6 human PRL secreting pituitary adenomas. In these cells resting [Ca2+]i levels were variable (mean +/- SE; 103.8 +/- 6.5, n = 25); the addition of 100 nM TRH caused a marked [Ca2+]i rise within 20 sec., the peak values ranging from 200 to 437 nM (285 +/- 10.8 nM, n = 10). The transients induced by TRH were composed by a rapid increase, due to mobilization of calcium from intracellular stores, followed within a few seconds by a lower plateau which was due to stimulated influx from the extracellular space. In fact, when EGTA and verapamil were applied after TRH they caused the Ca2+ plateau to dissipate rapidly. The addition of 1 microM dopamine (DA) caused a substantial decrease of resting [Ca2+]i (about 10-30%) as well as an inhibition of the plateau phase induced by TRH. The effect of DA completely depended on extracellular Ca2+. The TRH-induced transients observed in adenomatous cells were quite similar in size and time course to those recorded in normal rat lactotrophs. As previously observed in rat lactotrophs, in adenomatous cells treatment with pertussis toxin (PTx, 1 microgram/ml for 4 h) was unable to affect the [Ca2+]i transients induced by TRH while completely abolished the effect of DA. The effects of TRH on in vivo and in vitro PRL secretion were also evaluated. Before surgery, no patient showed a positive response to the iv administration of 200 micrograms TRH (serum PRL levels: 95 +/- 62 ng/ml in basal conditions vs 124 +/- 92 after TRH, P = NS).(ABSTRACT TRUNCATED AT 250 WORDS)


[Left ventricular projectile migration after an accidental close-range gunshot wound].
We report the case of a 24-year-old female after sustaining a shotgun wound in the left upper extremity and chest. Initial emergency diagnostics revealed numerous shotgun pellets scattered throughout the left-side soft tissue, chest and upper lung lobe with one pellet having migrated into the left ventricle of the heart.Due to the devastating injury pattern, gunshot wounds are interdisciplinarily challenging and should include extended initial diagnostics, such as contrast agent CT. The potential toxicity of elevated lead blood levels have to be taken into further account.


Evaluation of neutralizing antibodies to type A, B, E, and F botulinum toxins in sera from human recipients of botulinum pentavalent (ABCDE) toxoid.
Twenty-five serum specimens from personnel immunized with botulinum pentavalent toxoid (ABCDE) had titers of neutralizing antibodies to type A (5.7 to 51.6 IU/ml), type B (0.75 to 18 IU/ml), and type E (0.61 to 10 IU/ml) botulinum toxins. Titers for one type could not be used to predict titers for another type in individuals receiving the toxoid. Cross-neutralizing antibodies to type F botulinum toxin were not detected (less than 0.0125 IU/ml).


[Breast conserving treatment in patients with early detection of breast cancer].
Kujawsko-pomorskie province is a region with high morbidity and death-rate from breast cancer. One method of detected less advanced forms of breast cancer and increased number of patients with BCT having prophylactic medical examination. The aim of the study was the treatment evaluation of patients with noninvasive and invasive cancer treated with BCT, screening-detected and non-screening detected. Prophylactic mammography for breast cancer was taken in three medical centers. First one so called "mobile" was localized in the health service center, second one in the bus with the mammography reaching distant areas and third one was performing examinations locally. There were 63401 people examined for breast cancer (age 35 -79), detected 288 breast cancers (0.54% of examined population). 260 of them were operated on. 1149 breast cancers were detected in non-screening group. The number of detected noninvasive cancers, their sizes and methods of treatment were analysed. Twelve of 260 (4,62%) cancers detected in screening patients were carcinoma noninvasive and 34 invasive cancers treated with BCT. In non-screening patients 20 carcinoma noninvasive and 104 invasive cancers were found and treated with BCT The number of patients with noninvasive and invasive cancers treated with BCT in prophylactic group is statistically higher. Sizes and clinical stages of malignant tumours detected in both groups were not different 1. Prophylactic breast cancer examinations increase the number of noninvasive cancers. 2. Breast cancer prophylactic examinations increase the number of patients treated with BCT.


Factors affecting the pregnancy rate after microsurgical reversal of tubal ligation.
To evaluate the factors affecting the pregnancy rate after microsurgical reversal of tubal ligation. Retrospective clinical study. Private practice affiliated with a tertiary care center. One hundred twenty-eight consecutive patients who underwent tubal reversal between October 1992 and May 2001. Microsurgical tubal reanastomosis performed by a single surgeon. Subsequent pregnancy rates were evaluated with Fisher's exact tests and logistic regression according to clinical characteristics of patients. The pregnancy rate was 85.7% (54 out of 63) in patients <or=35 years of age vs. 45.5% (10 out of 22) in patients >35 years. The odds ratio (OR) between the two age groups was 7.20, with a 95% confidence interval (CI) of 2.41 to 21.55. The pregnancy rate was 85.4% (35 out of 41) in patients with body mass index (BMI) <or=25 compared with 65.9% (29 out of 44) in patients with BMI >25 (OR 3.02; CI 1.04 to 8.77). Patients sterilized <or=8 years had a pregnancy rate of 87.2% (34 out of 39), vs. 65.2% (30 out of 46) in patients sterilized >8 years (OR 3.63; CI 1.19 to 11.09). Age was the primary statistically significant factor affecting pregnancy rate in tubal reversal patients. Body mass index and duration of sterilization had smaller, but statistically significant, associations with pregnancy rate.


Vestibular toxicity of cis-2-pentenenitrile in the rat.
cis-2-Pentenenitrile, an intermediate in the synthesis of nylon and other products, causes permanent behavioral deficits in rodents. Other low molecular weight nitriles cause degeneration either of the vestibular sensory hair cells or of selected neuronal populations in the brain. Adult male Long-Evans rats were exposed to cis-2-pentenenitrile (0, 1.25, 1.50, 1.75, or 2.0mmol/kg, oral, in corn oil) and assessed for changes in open field activity and rating scores in a test battery for vestibular dysfunction. Surface preparations of the vestibular sensory epithelia were observed for hair cell loss using scanning electron microscopy. A separate experiment examined the impact of pre-treatment with the universal CYP inhibitor,1-aminobenzotriazole, on the effect of cis-2-pentenenitrile on vestibular rating scores. The occurrence of degenerating neurons in the central nervous system was assessed by Fluoro-Jade C staining. cis-2-Pentenenitrile had a dose-dependent effect on body weight. Rats receiving 1.50mmol/kg or more of cis-2-pentenenitrile displayed reduced rearing activity in the open field and increased rating scores on the vestibular dysfunction test battery. Hair cell loss was observed in the vestibular sensory epithelia and correlated well with the behavioral deficits. Pre-treatment with 1-aminobenzotriazole blocked the behavioral effect. Fluoro-Jade C staining did not reveal significant neuronal degeneration in the central nervous system apart from neurite labeling in the olfactory glomeruli. We conclude that cis-2-pentenenitrile causes vestibular toxicity in a similar way to allylnitrile, cis-crotononitrile and 3,3'-iminodipropionitrile (IDPN), and also shares other targets such as the olfactory system with these other nitriles. The present data also suggest that CYP-mediated bioactivation is involved in cis-2-pentenenitrile toxicity.


Optical studies of membrane state during action potential propagation.
One of the most striking phenomena in biology is the action potential (AP), a nonlinear pulse with threshold and amplitude saturation (all-or-none-behavior) that propagates along neurons and other cells. In the classical interpretation the AP is considered to be an electrical phenomenon - a regenerating current flowing in a "biological cable". In contrast, the thermodynamic interpretation has emphasized that conservation laws necessitate pulses and that pulses must manifest as transient changes of all observables of the system (electrical, mechanical, thermal, etc.). It is a key prediction of the latter approach that the cell membrane must undergo thermodynamic state changes during an AP. In order to characterize the thermodynamic state of an excitable membrane, plant cells (Chara australis) were stained with Di-4-ANEPPDHQ. The location of the dye in the cell membrane was confirmed by confocal microscopy and changes of fluorescence emission were investigated as a function of temperature and extracellular pH. In parallel, emission of the dye was studied in artificial lipid vesicles (DMPC, DMPS) in the vicinity of the main transition temperature. In all these systems, the emission spectrum shifted as a function of membrane state. This shift became nonlinear and was maximal when the membrane underwent a transition (∂λ∂T∼(6-10)nm°C-1). In the excitable cell Di-4-ANEPPDHQ exhibited a transient blueshift by ∼7 nm during an AP. A blueshift also occurred upon cooling and extracellular acidification. These results provided evidence for a sequence of state changes during an AP in which the cellular membrane condenses followed by expansion. This finding is in line with the thermodynamic interpretation of cellular excitability. Future studies should confirm/falsify these findings with other fluorescent dyes or state-sensitive techniques.


Fluoro-functionalized ionic covalent organic frameworks (F-iCOFs) for highly selective enrichment and sensitive determination of perfluorinated sulfonates by MALDI-MS.
An easily prepared fluoro-functionalized ionic covalent organic framework (F-iCOF) has been implemented into MALDI-TOF MS, enabling the highly selective enrichment and sensitive determination of perfluorinated sulfonate (PFS) contaminants in a rapid and convenient manner. The good thermal stability and excellent optical absorption properties of F-iCOF makes it a brilliant matrix with no background noise. Moreover, benefitting from the large surface area, appropriate pore size, good water dispersibility, and abundant fluorine atom and cationic characteristic of F-iCOF, it exhibited superior adsorption capacity and enrichment selectivity towards PFSs. Good signal responses for PFSs were obtained in the presence of various interfering compounds such as BSA, HA, or even more than 100-fold excess of glutamic acid and similar in structure sodium alkyl sulfonates, highlighting the specific selectivity of F-iCOF. Calibration curves for potassium perflurobutane sulfonate (PFBSK) in tap water and whole blood were established with good linear correlation in the range 1-500 pg mL-1. The limits of detection and quantification for PFBSK were as low as 0.04 pg mL-1 and 0.05 pg mL-1, respectively, which are comparable or better than the existing methods for the determination of PFSs.


Zn-Metal-Organic Framework Derived Ordered Mesoporous Carbon-Based Nanostructure for High-Performance and Universal Multivalent Metal Ion Storage.
Metal-organic framework (MOF) derivatives promise great potential in energy storage and conversion because of their excellent tunability in both the active metal sites, organic links, and the overall structures down to atomic and up to mesoscale. Nevertheless, a big challenge is to precisely control and thoroughly understand the actual MOF-to-derivative conversion process to realize the template-free synthesis of the MOF-derived ordered mesoporous materials. Here, a class of ordered mesoporous N-doped carbon nanoflakes is presented with slit-shaped pores synthesized by one-step pyrolysis of Zn1 Cux -MOF, where the Cu doping plays a critically important direction-inducing function on the dissociation of organic ligands during the pyrolysis. Benefiting from the uniquely ordered mesoporous structure and large specific surface area (910 m2 g-1 ), the Zn1 Cux -MOF-derived ordered mesoporous carbon nanoflakes present outstanding electrochemical storage performance for multivalent metal ions, such as Mg2+ , Ca2+ , Co2+ , Ni2+ , Al3+ , and Zn2+ , demonstrating the universal nature of the slit-shaped pores in enabling the multivalent metal ions for energy storage. Moreover, the assembled flexible Zn-ion hybrid supercapacitor (ZHSC) delivers a high specific capacity of 134 mAh g-1 at 0.5 A g-1 , excellent cycling and mechanical stability, showing great application potential in the new generation energy storage devices.


Fitting the two-compartment model in DCE-MRI by linear inversion.
Model fitting of dynamic contrast-enhanced-magnetic resonance imaging-MRI data with nonlinear least squares (NLLS) methods is slow and may be biased by the choice of initial values. The aim of this study was to develop and evaluate a linear least squares (LLS) method to fit the two-compartment exchange and -filtration models. A second-order linear differential equation for the measured concentrations was derived where model parameters act as coefficients. Simulations of normal and pathological data were performed to determine calculation time, accuracy and precision under different noise levels and temporal resolutions. Performance of the LLS was evaluated by comparison against the NLLS. The LLS method is about 200 times faster, which reduces the calculation times for a 256 × 256 MR slice from 9 min to 3 s. For ideal data with low noise and high temporal resolution the LLS and NLLS were equally accurate and precise. The LLS was more accurate and precise than the NLLS at low temporal resolution, but less accurate at high noise levels. The data show that the LLS leads to a significant reduction in calculation times, and more reliable results at low noise levels. At higher noise levels the LLS becomes exceedingly inaccurate compared to the NLLS, but this may be improved using a suitable weighting strategy. Magn Reson Med 76:998-1006, 2016. © 2015 Wiley Periodicals, Inc.


A cleavable cytolysin-neuropeptide Y bioconjugate enables specific drug delivery and demonstrates intracellular mode of action.
Myxobacterial tubulysins are promising chemotherapeutics inhibiting microtubule polymerization, however, high unspecific toxicity so far prevents their application in therapy. For selective cancer cell targeting, here the coupling of a synthetic cytolysin to the hY1-receptor preferring peptide [F(7),P(34)]-neuropeptide Y (NPY) using a labile disulfide linker is described. Since hY1-receptors are overexpressed in breast tumors and internalize rapidly, this system has high potential as peptide-drug shuttle system. Molecular characterization of the cytolysin-[F(7),P(34)]-NPY bioconjugate revealed potent receptor activation and receptor-selective internalization, while viability studies verified toxicity. Triple SILAC studies comparing free cytolysin with the bioconjugate demonstrated an intracellular mechanism of action regardless of the delivery pathway. Treatments resulted in a regulation of proteins implemented in cell cycle arrest confirming the tubulysin-like effect of the cytolysin. Thus, the cytolysin-peptide bioconjugate fused by a cleavable linker enables a receptor-specific delivery as well as a potent intracellular drug-release with high cytotoxic activity.


Validation of a patient classification through evaluation of the nursing staff degree of occupation.
The instrument of evaluation of the degree of occupation of nursing staff is centered on the activities of the staff. It generates an index indicating how "busy" the staff is during a given shift on a particular unit. It can be used to validate a patient classification system by level of nursing resources requirements.


Encephalopathy, hearing loss and retinal occlusions (Susac's syndrome): a new case.
We describe a young woman with retinal arteriolar occlusions, encephalopathy, and hearing loss. At present this disorder is known as Susac's syndrome, a microangiopathy of the brain and retina whose pathogenesis is, however, unknown. The article reviews the clinical features of this rare, but not unusual, syndrome that can easily be misdiagnosed as multiple sclerosis.


Carbohydrate-rich high-molecular-mass antigens are strongly recognized during experimental Histoplasma capsulatum infection.
During histoplasmosis, Histoplasma capsulatum soluble antigens (CFAg) can be naturally released by yeast cells. Because CFAg can be specifically targeted during infection, in the present study we investigated CFAg release in experimental murine histoplasmosis, and evaluated the host humoral immune response against high-molecular-mass antigens (hMMAg. >150 kDa), the more immunogenic CFAg fraction. Mice were infected with 2.2 x 10⁴ H. capsulatum IMT/HC128 yeast cells. The soluble CFAg, IgG anti-CFAg, IgG anti-hMMAg, and IgG-hMMAg circulating immune complexes (CIC) levels were determined by enzymelinked immunosorbent assay, at days 0, 7, 14, and 28 post-infection. We observed a progressive increase in circulating levels of CFAg, IgG anti-CFAg, IgG anti-hMMAg, and IgG-hMMAg CIC after H. capsulatum infection. The hMMAg showed a high percentage of carbohydrates and at least two main immunogenic components. We verified for the first time that hMMAg from H. capsulatum IMT/HC128 strain induce humoral immune response and lead to CIC formation during experimental histoplasmosis.


Urate nephropathy associated with impaired kinetic properties of hypoxanthine phosphoribosyl transferase in a 45-day-old infant.
We report a 45-day-old male infant who presented with anuric renal failure and fluid overload due to urate nephropathy consequent upon hyperuricemia with hyperuricosuria. His maternal uncle had undergone renal transplantation for chronic renal failure secondary to uric acid nephrolithiasis. The levels of hypoxanthine phosphoribosyl transferase (HPRT) and adenine phosphoribosyl transferase activity in the baby were found to be quantitatively normal. However, when the HPRT activity was measured at low substrate concentrations [phosphoribosyl pyrophosphate (PRPP) and hypoxanthine] and compared with usual assay conditions, the HPRT activity at lower PRPP was less in the propositus, suggesting altered enzyme kinetics. Apparent K (m(PRPP)) and V (max), but not K (m(hypoxanthine)), were then found to be higher in the propositus than the control range. This is the first case of urate nephropathy secondary to altered enzyme kinetics presenting as early as 45 days. Uric acid nephropathy should be considered in the differential diagnosis of unexplained acute kidney injury in infants. In such cases, quantitative tests for HPRT enzyme activity may not be sufficient and altered enzyme kinetics should also be investigated.


Coptisine inhibits Helicobacter pylori and reduces the expression of CagA to alleviate host inflammation in vitro and in vivo.
Helicobacter pylori (H. pylori) is a major pathogen colonized in the human stomach and is implicated in gastritis, peptic ulcer, and gastric carcinoma. Antibiotics are useful for eradicating H. pylori but failed for drug resistance, making it urgent to develop effective and safe drugs. Rhizoma Coptidis was reported as one of the most effective Chinese medicines to treat H. pylori-related gastrointestinal diseases, while the precise antimicrobial mechanism remains unclear. Thus, it is of great significance to study the antimicrobial ingredients and corresponding mechanisms of Rhizoma Coptidis. To search for the most effective alkaloid against H. pylori in Rhizoma Coptidis and illustrate the probable mechanisms. Five main alkaloids in Rhizoma Coptidis were isolated. Minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) were tested to determine the most effective one. Bacterial growth experiments, Annexin V-FITC/PI staining, TUNEL staining, and transmission electron microscopy (TEM) were performed to further study the anti-H. pylori activity of coptisine (Cop). The in vivo effect of Cop on H. pylori eradication rate and H. pylori-induced inflammation was investigated in mice. Transcriptomics was used to understand the underlying mechanism of eradicating H. pylori and reducing host inflammation. Western blot, RT-PCR, and ELISA experiments were utilized and confirmed that cagA was one of the targets of Cop. According to the MIC and MBC, Cop was the most effective alkaloid against H. pylori, especially with no drug resistance developed. In vitro experiments showed that Cop inhibited H. pylori by inducing DNA fragmentation, phosphatidylserine exposure, and membrane damage. Cop (150 mg/kg/day) effectively eradicated H. pylori in mice and reduced the levels of IL-2 and IL-6 to relieve gastric inflammation. Transcriptomic analysis revealed that virulence factor cagA was one of the hub genes associated with the inflammation-improving effect of Cop. That is, Cop could decrease the expression of CagA and subsequently reduce the translocation of CagA to gastric epithelial cells, thereby improving the morphology of hummingbird-like phenotype induced by CagA and alleviating inflammation. Cop is the most effective alkaloid in Rhizoma Coptidis and might act through multiple mechanisms for H. pylori eradication along with reducing the expression of CagA to alleviate inflammation.


Growth and development of the mouse retinal pigment epithelium. II. Cell patterning in experimental chimaeras and mosaics.
The retinal pigment epithelium (PE), with pigmentation as a cell-autonomous marker, was analyzed in three types of mice: congenic pigmented----albino chimaeras, X-inactivation mosaics (Cattanach's translocation), and mosaics homozygous for the pink-eyed unstable mutation, which contain rare fully pigmented cells. In 10 chimaeric and 34 X-inactivation eyes, the proportionate mix in the right and left eyes of an individual animal was similar, the mix was approximately constant in all parts of a given eye, average patch size was larger toward the periphery of the PE, and peripheral patches tended to be elongated in the radial dimension. In all 44 whole mounts from pink-eyed unstable mutants, patches of 1-12 pigmented cells, each representing a single clone, were scattered throughout the PE; they tended to be larger with increasing distance from the optic nerve head. The collective data are consistent with significant cell mixing prior to specification of the two eye fields, during early organ-forming stages, and during later development of the PE. The tendency of peripheral patches to orient radially reflects the edge-biased pattern of cell proliferation in the PE. Cell mixing appears to be more prominent posteriorly in the PE sheet; growth proceeds anteriorly for more generations.


Hematopoietic Progenitor Cell Harvesting Is Feasible after Treatment with Brentuximab Vedotin in CD30(+) Lymphoma Patients Who Received Multiple Prior Lines of Treatment.
Brentuximab vedotin (BV), an antibody-drug conjugate that targets CD30, induces high response rates in CD30(+) lymphoid malignancies. It is unknown if BV use affects procurement of autologous CD34(+) stem cells and hematopoietic engraftment after autologous stem cell transplantation (ASCT). We examined 42 patients treated with BV before mobilization. Median times from diagnosis to transplantation, from initial BV treatment to transplantation, and from last BV treatment to stem cell collection were 21 months (range, 10 to 210), 5 months (range, 1.5 to 16.8), and 30 days (range, 2 to 280), respectively. Mobilization was successful on the first attempt in 38 patients (90.4%). The median number of infused CD34(+) cells was 5.46 × 10(6)/kg (range, 1.65 to 54.78 × 10(6)/kg). The median times to neutrophil and platelet engraftment were 10 (range, 9 to 13), and 10.5 days (range, 7 to 35), respectively. BV before high-dose chemotherapy-ASCT did not adversely affect peripheral blood stem cell mobilization and subsequent engraftment in a cohort of heavily pretreated patients with CD30(+) lymphomas.


Multimodality cancer care and implications for episode-based payments in cancer.
Most patients receiving multimodality cancer care receive care from different practices. Therefore, episode-based payments in oncology must hold multiple providers accountable for costs and quality.


Differential diagnosis of Perkinsus species by polymerase chain reaction-restriction fragment length polymorphism assay.
Perkinsosis is an infection of marine molluscs caused by the protistan parasites of the genus Perkinsus, which has been classified by the OIE as a disease that warrants notification. In the present study, we have applied a molecular genetic approach to develop an optional method for the specific identification of Perkinsus species. A species-specific polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay of the rRNA ITS region was developed to identify and distinguish among Perkinsus species. A taxonomic key was established that allows successful identification of Perkinsus species using a single restriction enzyme (Rsa I) to discriminate P. chesapeaki and P. marinus or by a combination of two endonucleases (Rsa I plus Hinf I) to discriminate P. olseni and P. mediterraneus. In order to validate the RFLP assay, the PCR products were cloned and sequenced, and its phylogenetic affinity was determined. Phylogenetic analysis confirmed the specific identification carried out by RFLPs. Herein is the first report of P. olseni in Manila clams from the NW Adriatic Sea (Italy), which we identified by employing this method. The PCR-RFLP assay herein described may be useful to provide accurate, rapid and inexpensive identification of Perkinsus species, and may aid in ongoing epizooetiological studies and diseases control programmes.


Lung adenocarcinoma from East Asian never-smokers is a disease largely defined by targetable oncogenic mutant kinases.
To determine the proportion of lung adenocarcinomas from East Asian never-smokers who harbor known oncogenic driver mutations. In this surgical series, 52 resected lung adenocarcinomas from never-smokers (< 100 cigarettes in a lifetime) at a single institution (Fudan University, Shanghai, China) were analyzed concurrently for mutations in EGFR, KRAS, NRAS, HRAS, HER2, BRAF, ALK, PIK3CA, TP53 and LKB1. Forty-one tumors harbored EGFR mutations, three harbored EML4-ALK fusions, two harbored HER2 insertions, and one harbored a KRAS mutation. All mutations were mutually exclusive. Thus, 90% (47 of 52; 95% CI, 0.7896 to 0.9625) of lung adenocarcinomas from never-smokers were found to harbor well-known oncogenic mutations in just four genes. No BRAF, NRAS, HRAS, or LKB1 mutations were detected, while 15 had TP53 mutations. Four tumors contained PIK3CA mutations, always together with EGFR mutations. To our knowledge, this study represents the first comprehensive and concurrent analysis of major recurrent oncogenic mutations found in a large cohort of lung adenocarcinomas from East Asian never-smokers. Since drugs are now available that target mutant EGFR, HER2, and ALK, respectively, this result indicates that prospective mutation testing in these patients should successfully assign a targeted therapy in the majority of cases.


The amelioration of hyperglycemia in streptozotocin-induced diabetic rats after the intraportal transplantation of an insufficient number of islets by nicotinamide treatment.
The purpose of the present study was to determine whether or not hyperglycemia in streptozotocin (STZ)-induced diabetic rats after the intraportal transplantation of an insufficient number of isogenic islets can be ameliorated by nicotinamide treatment. WKA/Qdj (RT 1u) rats were used both as donors and recipients. Islets were isolated by the collagenase technique. A total of 350 islets was transplanted into the liver via the portal vein of the STZ-induced diabetic rats. Either nicotinamide (NA, 0.5 g/kg) or a vehicle (saline) was administered ip once a day for 60 days after transplantation. All the diabetic rats without islet transplantation remained hyperglycemic irrespective of the NA treatment. All the recipients (n = 12) bearing the islet grafts and treated with saline remained hyperglycemic (> 400 mg/dl) at 60 days after transplantation. In marked contrast, all the recipients (n = 18) with islet grafts and treated with NA became normoglycemic (< 200 mg/dl) at 16.2 +/- 7.1 days (mean +/- SD) after transplantation. Morphologically, islets were easily found in the liver of the recipients. Aldehyde-fuchsin stain revealed that the beta cells in the islet grafts of the NA treated recipients were well granulated, whereas those treated with saline were degranulated. The insulin content of the liver bearing the grafts treated with either NA or saline was 116.3 +/- 26.0 micrograms/liver (n = 4) or 5.7 +/- 2.2 micrograms (n = 4), respectively, while that of 350 donor islets was 29.4 +/- 2.5 micrograms (n = 5). The insulin content of the pancreas in the NA- or saline-treated recipients was 27.3 +/- 10.6 micrograms/pancreas (n = 4) or 2.7 +/- 1.2 micrograms (n = 4), respectively, while those of the pancreas from the diabetic rats without transplantation was 1.9 +/- 0.7 micrograms (n = 4) or 1.6 +/- 0.8 micrograms (n = 5), respectively. These findings clearly demonstrate that the hyperglycemia in the STZ-diabetic recipients after transplantation of an insufficient number of islets can be ameliorated while, in addition, the islet mass in the liver as well as the endogenous pancreas both increase in size with nicotinamide treatment.


Mad, bad and dangerous to know: dimensions and measurement of attitudes toward injecting drug users.
Attitudes toward injecting drug users were assessed using a 53-item questionnaire which was administered to 143 workers at a drug and alcohol research unit and an AIDS treatment facility. Factor analysis revealed three interpretable dimensions: intravenous drug use as a matter of both public concern and personal inadequacy; intravenous drug users as criminals who should be removed from society; and social avoidance of, and personal distaste for, intravenous drug users. The scale and subscales had good test-retest reliability and internal consistency. Its potential use as a measure of attitudes toward injecting drug users for both treatment research and AIDS research is discussed.


Khalas date flavonoids inhibited cell viability, induced apoptosis and expression of the pro-autophagy LC3-B gene in human hepatocellular carcinoma cells (HepG2).
Autophagy is a protective mechanism important in human diseases as cancer. We evaluated the impact of khalas date extract (KDE) (20-60 mg/mL) on cell viability, morphological changes, DNA fragmentation and gene expression of LC3B-II associated with autophagosome on HepG2 cell line. The GC/MS identification of KDE showed its high content of flavonoids including quercetin, myricetin, kaempferol and catechol. KDE reduced cell viability of HepG2 with IC50 (31.52 mg/mL). Cells treated with KDE showed two band of DNA fragments at (30 and 40 mg) indicating that KDE induced DNA damage and apoptosis in HepG2. The analysis RT-PCR data showed a 0.2-fold increase in the expression of LC3-B in the cells treated with KDE versus control. We concluded that, KDE flavonoids such as quercetin, myricetin kaempferol exhibited anticancer properties manifested by inhibition of HepG2 cell viability and induction of apoptosis and upregulation of the pro-autophagy LC3-B gene.


Palliative Care for Parkinson Disease.
Palliative care (PC) is an approach to the care of persons affected by serious illness that focuses on reducing suffering by addressing medical, psychosocial, and spiritual needs. Persons living with Parkinson disease have PC needs that begin at the time of diagnosis and continue throughout the course of the illness including nonmotor symptom burden, caregiver distress, grief, and increased mortality. Primary PC refers to essential PC skills that may be practiced by nonpalliative medicine specialists to improve outcomes for their patients.


Cost-effectiveness and future implications for cardiovascular imaging.
This review highlights the current economic climate for health care and the evidentiary standards that are increasingly applied to appropriate use of cardiovascular imaging. Additionally, the evidence on cost efficiency and effectiveness is explored in this review. Ongoing multicentre registries and clinical trials will further enrich this evidence base with regard to value-based imaging strategies that provide enhanced effectiveness and efficiency resulting in improved patient outcomes.


Genetic dissection of psychopathological symptoms: insomnia in mood disorders and CLOCK gene polymorphism.
We investigated the possible effect of the 3111T/C CLOCK gene polymorphism on sleep disorders in a sample of 620 patients affected by major depressive disorder (MDD) and bipolar disorder (BP). We detected a significantly higher recurrence of initial (P = 0.0001), middle (P = 0.0009), and early (P = 0.0008) insomnia in homozygotes for the C variant and a similar trend concerning decreased need of sleep in BP (P = 0.0074). Other demographic and clinical features were found not related with CLOCK polymorphisms. This preliminary observation leads to hypothesize a possible involvement of the CLOCK gene polymorphism in the sleep disregulations in MDD and BP.


B-Cell Epitope Predictions Using Computational Methods.
Identifying protein antigenic epitopes that are recognizable by antibodies is a key step in immunologic research. This type of research has broad medical applications, such as new immunodiagnostic reagent discovery, vaccine design, and antibody design. However, due to the countless possibilities of potential epitopes, the experimental search through trial and error would be too costly and time-consuming to be practical. To facilitate this process and improve its efficiency, computational methods were developed to predict both linear epitopes and discontinuous antigenic epitopes. For linear B-cell epitope prediction, many methods were developed, including PREDITOP, PEOPLE, BEPITOPE, BepiPred, COBEpro, ABCpred, AAP, BCPred, BayesB, BEOracle/BROracle, BEST, LBEEP, DRREP, iBCE-EL, SVMTriP, etc. For the more challenging yet important task of discontinuous epitope prediction, methods were also developed, including CEP, DiscoTope, PEPITO, ElliPro, SEPPA, EPITOPIA, PEASE, EpiPred, SEPIa, EPCES, EPSVR, etc. In this chapter, we will discuss computational methods for B-cell epitope predictions of both linear and discontinuous epitopes. SVMTriP and EPCES/EPCSVR, the most successful among the methods for each type of the predictions, will be used as model methods to detail the standard protocols. For linear epitope prediction, SVMTriP was reported to achieve a sensitivity of 80.1% and a precision of 55.2% with a fivefold cross-validation based on a large dataset, yielding an AUC of 0.702. For discontinuous or conformational B-cell epitope prediction, EPCES and EPCSVR were both benchmarked by a curated independent test dataset in which all antigens had no complex structures with the antibody. The identified epitopes by these methods were later independently validated by various biochemical experiments. For these three model methods, webservers and all datasets are publicly available at http://sysbio.unl.edu/SVMTriP , http://sysbio.unl.edu/EPCES/ , and http://sysbio.unl.edu/EPSVR/ .


Bisphosphonate associated femoral stress fracture distal to an orthopaedic implant: They are predictable!
Stress fractures are uncommon and often occur in young athletes with high intensity physical activity. These stress fractures occur in weight bearing long bones. Recent literature suggests association of thigh pain, tension side cortical thickening of femoral shaft or a femoral subtrochanteric atypical stress fractures in patients on long term bisphosphonate therapy. The reports of peri-implant bisphosphonate associated atypical stress fractures are very rare. We describe a series of three cases of femoral shaft stress phenomenon around orthopaedic implants who presented with similar prodromal thigh pain and tension side cortical thickening. Two patients sustained fractures as the condition was not recognised despite presenting with prodromal symptoms and one patient with a stress riser who was treated prophylactically. Thus this series aims to highlight the importance of identifying the stress phenomenon around orthopaedic implants, be it intra or extra-medullary implants. The location of these fractures is just distal to the implants and are classically transverse fractures. The treatment of peri-implant stress fractures needs a personalised approach in every case with appropriate choice of implants.


Effects of pravastatin on apolipoprotein-specific high density lipoprotein subpopulations and low density lipoprotein subclass phenotypes in patients with primary hypercholesterolemia.
The HMG-CoA reductase inhibitor class of cholesterol-lowering agents reduces very low density lipoproteins (VLDL) and low density lipoproteins (LDL) and slightly increases high density lipoproteins (HDL). However, the effects of these agents on subclasses within the LDL and HDL fractions are not well understood. We have employed an HMG-CoA reductase inhibitor, pravastatin, to determine if LDL subclass phenotypes, as determined by gradient gel electrophoresis, and HDL particles containing both apolipoprotein (apo) A-I and A-II, Lp(AI w AII), and those containing apo A-I but not A-II, Lp(AI w/o AII) are affected by pravastatin (10 mg daily). Twenty-four subjects with LDL-cholesterol (LDL-C) > 160 mg/dl, triglyceride (TG) < 350 mg/dl and no recent myocardial infarction or secondary causes of hypercholesterolemia were enrolled. Compared with an age- and sex-matched normolipidemic reference group (controls), the hypercholesterolemic subjects had reduced levels of Lp(AI w/o AII) and increased levels of Lp(AI w AII) at baseline. In addition, both of their HDL subpopulations had significantly more small (7.0-8.2 nm) particles (P < 0.02 and 0.0001) but significantly fewer large (9.2-11.2 nm) particles (P < 0.002 and 0.0001). Pravastatin induced statistically significant (P < 0.001) reductions in plasma total C (15%), LDL-C (18%), and apo B (16%). While apo A-I and A-II levels increased 5% (P < 0.001) and 6% (P < 0.05), respectively, concentration, composition, and size abnormalities in Lp(AI w AII) and Lp(AI w/o AII) persisted. Lp(a), apo E and cholesteryl ester transfer protein (CETP) levels also did not change. Although changes in LDL subclass phenotypes were observed, all changes involved the intermediate phenotype, and no significant changes in LDL peak particle diameter were seen in either group. Interrelationships between CETP, LDL subclass phenotypes and HDL subpopulations were also seen. Although pravastatin decreased plasma apo B and LDL lipid concentrations, no major changes were seen in LDL subclass phenotypes or HDL subpopulations even in the presence of abnormalities associated with arteriosclerosis. Similarly, CETP, which is believed to play a role in HDL and LDL particle size distribution, did not change with pravastatin treatment. Further research is needed to determine the pathophysiological basis of abnormal HDL and LDL subclasses in hypercholesterolemia and explore methods of rectifying the abnormalities.


Outcome criteria in patients with peripheral arterial disease.
To adequately evaluate patients with chronic occlusive arterial disease several factors will need to be taken into account and documented. These include associated diseases such as diabetes mellitus. When surgical or endovascular therapy is applied, analysis of outcome must include the symptomatic status of the patient, the anatomic evidence of patency of the procedure and of the proximal and distal disease, the hemodynamic result, limb preservation, and mortality. All of these factors will provide a better global picture of the disease and information on how it can be best treated.


Orthodontic screws to extrude impacted maxillary canines.
The impaction of maxillary canines is a frequently encountered clinical problem in orthodontic practice. Patients' refusal to participate in long-term treatment or ankylosis of the impacted tooth result in various treatment difficulties. The aim of this study was to evaluate the possible role of mini-screws in the management of unerupted upper canines. In a series of 63 consecutive patients (27 males and 36 females, age range 14-49 years, mean 22.7 years) with a total of 69 impacted maxillary canines, each impacted tooth was surgically exposed and an attachment bonded. An intraosseous screw with an endosseous body and intraoral neck section was inserted into the premolar-molar interradicular space. Following soft tissue healing, orthodontic traction was initiated. After correction of the canine angulation, the mini-screw was removed and conventional orthodontic therapy completed. Of the 69 canines, 61 (88.41%) were extruded successfully. In the 7 cases that failed, skeletal anchorage spared both patients and clinicians the disappointment of customary long-term, unsuccessful orthodontic therapy. In one patient, the mini-screw was removed because of inflammation and pain before initiating orthodontic traction. Our results demonstrate that mini-screw anchorage should be taken into consideration when extrusion of an impacted canine is planned.


The role of fluconazole in the regulation of fatty acid and unsaponifiable matter biosynthesis in Schizochytrium sp. MYA 1381.
Schizochytrium has been widely used in industry for synthesizing polyunsaturated fatty acids (PUFAs), especially docosahexaenoic acid (DHA). However, unclear biosynthesis pathway of PUFAs inhibits further production of the Schizochytrium. Unsaponifiable matter (UM) from mevalonate pathway is crucial to cell growth and intracellular metabolism in all higher eukaryotes and microalgae. Therefore, regulation of UM biosynthesis in Schizochytrium may have important effects on fatty acids synthesis. Moreover, it is well known that UMs, such as squalene and β-carotene, are of great commercial value. Thus, regulating UM biosynthesis may also allow for an increased valuation of Schizochytrium. To investigate the correlation of UM biosynthesis with fatty acids accumulation in Schizochytrium, fluconazole was used to block the sterols pathway. The addition of 60 mg/L fluconazole at 48 h increased the total lipids (TLs) at 96 h by 16% without affecting cell growth, which was accompanied by remarkable changes in UMs and NADPH. Cholesterol content was reduced by 8%, and the squalene content improved by 45% at 72 h, which demonstrated fluconazole's role in inhibiting squalene flow to cholesterol. As another typical UM with antioxidant capacity, the β-carotene production was increased by 53% at 96 h. The increase of squalene and β-carotene could boost intracellular oxidation resistance to protect fatty acids from oxidation. The NADPH was found to be 33% higher than that of the control at 96 h, which meant that the cells had more reducing power for fatty acid synthesis. Metabolic analysis further confirmed that regulation of sterols was closely related to glucose absorption, pigment biosynthesis and fatty acid production in Schizochytrium. This work first reported the effect of UM biosynthesis on fatty acid accumulation in Schizochytrium. The UM was found to affect fatty acid biosynthesis by changing cell membrane function, intracellular antioxidation and reducing power. We believe that this work provides valuable insights in improving PUFA and other valuable matters in microalgae.


Environmental Breviatea harbour mutualistic Arcobacter epibionts.
Breviatea form a lineage of free living, unicellular protists, distantly related to animals and fungi. This lineage emerged almost one billion years ago, when the oceanic oxygen content was low, and extant Breviatea have evolved or retained an anaerobic lifestyle. Here we report the cultivation of Lenisia limosa, gen. et sp. nov., a newly discovered breviate colonized by relatives of animal-associated Arcobacter. Physiological experiments show that the association of L. limosa with Arcobacter is driven by the transfer of hydrogen and is mutualistic, providing benefits to both partners. With whole-genome sequencing and differential proteomics, we show that an experimentally observed fitness gain of L. limosa could be explained by the activity of a so far unknown type of NAD(P)H-accepting hydrogenase, which is expressed in the presence, but not in the absence, of Arcobacter. Differential proteomics further reveal that the presence of Lenisia stimulates expression of known 'virulence' factors by Arcobacter. These proteins typically enable colonization of animal cells during infection, but may in the present case act for mutual benefit. Finally, re-investigation of two currently available transcriptomic data sets of other Breviatea reveals the presence and activity of related hydrogen-consuming Arcobacter, indicating that mutualistic interaction between these two groups of microbes might be pervasive. Our results support the notion that molecular mechanisms involved in virulence can also support mutualism, as shown here for Arcobacter and Breviatea.


Surgical correction of epispadias associated with buried penis.
Isolated male epispadias is a rare entity with incidence of approximately 1 in 120,000 live births. Epispadias usually presents with a phimotic preputial orifice where glans is not visible and hence is also known as concealed epispadias. Buried penis in children is defined as a congenital insufficient penile skin with an unretractable foreskin that keeps the penis deep inside the pre-pubic fat. This congenital malformation of the penile envelopes is usually isolated. However, in some cases the concealed penis hides an underlying penile anomaly. We present surgical repair of a very rare case with concealed epispadias. A nine-month-old infant had buried his penis, and his mother was seeking his circumcision. Local examination revealed concealed penopubic epispadias. A pediatric surgeon operated on this patient using the modified partial penile disassembly technique. The patient was doing well at follow-up visits at one, three, and six months. There were no urethral stricture or obstructive urinary symptoms. The parents were satisfied with the cosmetic outcome. The embryogenesis and development of the urethra and the prepuce are linked. Urethral development defects (as in hypospadias or epispadias) are frequently coupled with faulty prepuce on the same side. The goal of surgical management for epispadias is to correct the dorsal chordee and reconstruct the epispadiac urethra and glans. Based on the cosmesis of the penis reconstruction, preservation of erectile function, and achieving urine continence, the outcome is evaluated. Concealed epispadias is frequently ignored because patients appear with buried penis, non-retractile prepuce, and a normal urine stream. Preoperative diagnosis and parent counseling are critical for the effective treatment of this uncommon entity. The modified partial penile disassembly procedure, in which the tunica albuginea is stitched to the pubic periosteum at 3 and 9 o'clock, can be used to correct buried epispadias.


Epitope-based vaccines: an update on epitope identification, vaccine design and delivery.
The basic premise of the epitope-based approach to vaccine development is that, in certain cases, the responses induced by the natural immunogen are not optimal, and can be improved upon by isolation or optimization of specific components of the response. For example, immunodominance is a key factor limiting the type and breadth of adaptive immunity. Recent advances in understanding the mechanisms of immunodominance thus represent an opportunity to further develop the epitope-based approach.


[Fragility and experiencing limits as a chance for development in old age--the meaning of the particular experiences of the aging body for identification and development as focused on the very old].
The main focus of this article is the meaning of particular experiences of the aging body for identity and development with respect to very old age. This experience of embodiment results from a dynamic development between unpleasant experiences of physical aging, positive bodily experiences of the pleasure of living, and reflections on this direct engagement with the aging body. The interaction of those three dimensions requires a constant rebalancing, which, in view of the frail body, becomes increasingly demanding. Beyond one's own experiences with aging through direct engagement with the body, established social relationships give room for an individual's physical nature and support the maintenance of identity and development. People who look after and care for old aged people have to recognize their own embodiment and have to acknowledge their aging body. This applies not only to contact with old aged people, but also requests that the potential for developing one's own identity be recognised. The inclusion of the body in the discourse on the aging process demands a mindset change in social gerontology and for the individual it means to submit oneself to the ethics of embodied existence.


Chitooligosaccharides for wound healing biomaterials engineering.
Chitooligosaccharides (CHOS) are oligomers of β-(1-4) linked N-acetylglucosamine and D-glucosamine that are produced from chitin or chitosan using different enzymatic or chemical methods. CHOS are water-soluble and non-cytotoxic with diverse bioactivities such as antibacterial, anti-inflammation, anti-obesity, anti-tumor and antioxidant. These biological features make CHOS promising compounds for several medical and food applications. In this review, we critically summarize the biological activities of CHOS in biomaterials engineering with a particular focus on CHOS applications for skin tissue healing and regeneration. We also present an updated overview of CHOS fabrications into wound dressing biomaterials for several in vitro and in vivo studies.