[Heparin resistance during cardiopulmonary bypass].
A 74-year-old man was scheduled for coronary artery bypass graft surgery with cardiopulmonary bypass. After intravenous heparin (200 U.kg-1), the activated clotting time (ACT) increased from 124 to 436 sec. However, it decreased to 128 sec immediately after cardiopulmonary bypass. The bypass was discontinued because the addition of heparin (200 U.kg-1) proved heparin resistance. The coronary artery bypass procedure was completed uneventfully without cardiopulmonary bypass. Several recent articles have reported that heparin resistance was corrected with antithrombin III concentrates, fresh frozen plasma, or argatroban. In this case, these drugs could not be used because the mechanism of heparin resistance remains uncertain. Thus, the off-pump technique is useful for unknown heparin resistance.


Pardaxin, a fish toxin peptide interaction with a biomimetic phospholipid/polydiacetylene membrane assay.
Pardaxin is a fish toxin belonging to the alpha-helical, pore-forming peptide family, used in toxicological and biophysical research to study toxin-cell and -lipid-artificial membranes interactions. We investigated the membrane interaction of two pardaxin analogues using a colorimetric phospholipid/polydiacetylene biomimetic assay. In this assay, polydiacetylene undergoes visible, concentration dependent, blue-red transformation induced through interactions of pardaxins with the vesicle membrane. Pardaxins P4 and P5, are composed of 33 amino acids, but differ in a single amino acid substitution at the carboxy-terminal (G31 to D31, respectively) known to decrease the pore forming activity. Addition of pardaxins in the colorimetric assay induced dose-dependent color transitions with different kinetics. The colorimetric analysis could distinguish between different pardaxins-membrane interaction profiles, suggesting bilayer surface association for P4 and vesicle membrane penetration for P5. The colorimetric assay could distinguish between pardaxins membrane interaction profiles although circular dichroism spectra of vesicle-interacting pardaxins did not indicate a significant difference in the secondary structure between these two toxin analogues. The colorimetric platform utilized in the present report represents a useful assay with general applications for studying membrane interactions of peptides in general and pore-forming toxins in particular, and may become an important tool for evaluating quantitative toxin structure-activity relationship.


The Association of Inflammatory Bowel Diseases with Autoimmune Disorders: A Report from the epi-IIRN.
There are conflicting data on the association between inflammatory bowel diseases [IBD] and autoimmunity disorders. The aim of this study was to explore this association including the effect of medications. We utilized health administrative data collected by three of the four health maintenance organizations [HMOs] in Israel, covering 52% of the country's population. We explored the prevalence of the following autoimmune disorders: insulin-dependent diabetes mellitus [IDDM], psoriasis, Sjögren syndrome, coeliac disease, systemic lupus erythematosus [SLE], primary sclerosis cholangitis [PSC] and autoimmune thyroiditis, among all IBD patients vs non-IBD controls. Case ascertainment was determined according to validated computerized algorithms. In total, 12625 IBD patients were compared to 12625 controls. A total of 1395 [11.1%] IBD patients had at least one autoimmune disease compared with 740 [5.9%] of non-IBD controls (odds ratio [OR] = 1.99 [95% confidence interval 1.81-2.19]; p < 0.05); all autoimmune diseases, except for thyroiditis, were more prevalent among IBD patients. Adjusted for confounding variables, anti-tumour necrosis factor [anti-TNF] medications were associated with a higher prevalence of psoriasis (54 [5.7%] in IBD vs 177 [4.1%] in controls; OR = 1.50 [1.07-2.08]; p < 0.05) but lower prevalence of Sjögren (1 [0.1%] vs 39 [0.9%]; OR [95% CI] = 0.13 [0.02-0.94]; p < 0.05) and coeliac disease (11 [1.2%] vs 68 [1.6%]; OR [95% CI] = 0.51 [0.27-0.99]; p < 0.05). Thiopurines and 5-aminosalicylates were not associated with any autoimmune disorder. IBD is associated with all autoimmune diseases explored here except for thyroiditis. Anti-TNF users have a higher prevalence of psoriasis, and lower prevalence of Sjögren and coeliac disease.


Identification of Potential Diagnostic and Prognostic Biomarkers for Gastric Cancer Based on Bioinformatic Analysis.
Background: Gastric cancer (GC) is one of the most prevalent cancers all over the world. The molecular mechanisms of GC remain unclear and not well understood. GC cases are majorly diagnosed at the late stage, resulting in a poor prognosis. Advances in molecular biology techniques allow us to get a better understanding of precise molecular mechanisms and enable us to identify the key genes in the carcinogenesis and progression of GC. Methods: The present study used datasets from the GEO database to screen differentially expressed genes (DEGs) between GC and normal gastric tissues. GO and KEGG enrichments were utilized to analyze the function of DEGs. The STRING database and Cytoscape software were applied to generate protein-protein network and find hub genes. The expression levels of hub genes were evaluated using data from the TCGA database. Survival analysis was conducted to evaluate the prognostic value of hub genes. The GEPIA database was involved to correlate key gene expressions with the pathological stage. Also, ROC curves were constructed to assess the diagnostic value of key genes. Results: A total of 607 DEGs were identified using three GEO datasets. GO analysis showed that the DEGs were mainly enriched in extracellular structure and matrix organization, collagen fibril organization, extracellular matrix (ECM), and integrin binding. KEGG enrichment was mainly enriched in protein digestion and absorption, ECM-receptor interaction, and focal adhesion. Fifteen genes were identified as hub genes, one of which was excluded for no significant expression between tumor and normal tissues. COL1A1, COL5A2, P4HA3, and SPARC showed high values in prognosis and diagnosis of GC. Conclusion: We suggest COL1A1, COL5A2, P4HA3, and SPARC as biomarkers for the diagnosis and prognosis of GC.


A decellularized porcine pulmonary valved conduit embedded with gelatin.
To prepare a tissue-engineered pulmonary valved conduit (PVC) with good tensile strength and biocompatibility. Sixty adult porcine PVCs were used to determine the optimal decellularization time. Five juvenile porcine decellularized PVCs and five juvenile porcine crosslinked PVCs were subsequently prepared according to the optimized decellularization and crosslinking methods. All PVCs were implanted into juvenile sheep for 8 months and then were harvested for staining. With a low concentration of detergent (0.25% Triton X-100+0.25% sodium deoxycholate), the decellularization effect on porcine PVCs was complete by 24 hours, and there was minimal damage to the matrix. Gelatin embedding and 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC) crosslinking improved the biomechanical properties of decellularized PVCs and reduced their immunogenicity. After implantation, the diameter and thickness of the PVCs in the decellularized and crosslinked groups increased significantly. In both groups, the conduits were unobstructed, with soft and smooth inner walls and without thrombosis, ulceration or neoplasia. The valves slightly degenerated with mild to moderate regurgitation. CD31-positive endothelial cells were visible on the inner surface of the conduits and valves. Scattered smooth muscle actin-positive cells were found in the middle layer of the conduit. The percentage of CD4- and CD68-positive cells and the calcium content were highest in decellularized porcine PVCs and lowest in ovine PVCs. The percentage of the matrix that was laminin-positive in decellularized and crosslinked porcine PVCs was lower than it was in ovine PVCs. Gelatin-embedded and EDC-crosslinked porcine PVCs can be "hosted" in sheep, with good biocompatibility, growth potential, and reduced calcification.


Influence of procedure classification on process variability and parameter uncertainty of surgical case durations.
Predictive variability of operating room (OR) times influences decision making on the day of surgery including when to start add-on cases, whether to move a case from one OR to another, and where to assign relief staff. One contributor to predictive variability is process variability, which arises among cases of the same procedure(s). Another contributor is parameter uncertainty, which is caused by small sample sizes of historical data. Process variability was quantified using absolute percentage errors of surgeons' bias-corrected estimates of OR time. The influence of procedure classification on process variability was studied using a dataset of 61,353 cases, each with 1 to 5 scheduled and actual Current Procedural Terminology (CPT) codes (i.e., a standardized vocabulary). Parameter uncertainty's sensitivity to sample size was quantified by studying ratios of 90% prediction bounds to medians. That studied dataset of 65,661 cases was used previously to validate a Bayesian method to calculate 90% prediction bounds using combinations of surgeons' scheduled estimates and historical OR times. (1) Process variability differed significantly among 11 groups of surgical specialty and case urgency (P < 0.0001). For example, absolute percentage errors exceeded the overall median of 22% for 57% of urgent spine surgery cases versus 42% of elective spine surgery cases. (2) Process variability was not increased when scheduled and actual CPTs differed (P = 0.23 without and P = 0.47 with stratification based on the 11 groups), because most differences represented known (planned) options inherent to procedures. (3) Process variability was not associated with incidence of procedures (P = 0.79), after excluding cataract surgery, a procedure with high relative variability. (4) Parameter uncertainty from uncommon procedures (0-2 historical cases) accounted for essentially all of the uncertainty in decisions dependent on estimates of OR times. The Bayesian method moderated the effect of small sample sizes on uncertainty in estimates of OR times. In contrast, from prior work, the use of broad categories of procedures reduces parameter uncertainty but at the expense of increased process variability. For procedures with few historic data, the Bayesian method allows for effective case duration prediction, permitting use of detailed procedure descriptions. Although fine resolution of scheduling procedures increases the chance of performed procedure(s) differing from scheduled procedure(s), this does not increase process variability. Future studies need both to address differences in process variability among specialties and accept the limitation that findings from one may not apply to others.


Euler fluid in two dimensions: Statistical approach.
We use Kirchhoff's vortex formulation of 2D Euler fluid equations to explore the equilibrium state to which a 2D incompressible fluid relaxes from an arbitrary initial flow. The vortex dynamics obeys Hamilton's equations of motion with x and y coordinates of the vortex position forming a conjugate pair. A state of fluid can, therefore, be expressed in terms of an infinite number of infinitesimal vortices. If the vortex dynamics is mixing, the final equilibrium state of the fluid should correspond to the maximum of Boltzmann entropy, with the constraint that all the Casimir invariants of the fluid must be preserved. This is the fundamental assumption of Lynden-Bell's theory of collisionless relaxation. In this paper, we will present a Monte Carlo method which allows us to find the maximum entropy state of the fluid starting from an arbitrary initial condition. We will then compare this prediction with the results of molecular dynamics simulation and demonstrate that the final state to which the fluid evolves is, actually, very different from that corresponding to the maximum of entropy. This indicates that the mixing assumption is not correct. We will then present a different approach based on core-halo distribution which allows us to accurately predict the final state to which the fluid will relax, starting from an arbitrary initial condition.


Racial Differences and Contributory Cardiovascular and Non-Cardiovascular Risk Factors Towards Chronic Kidney Disease Progression.
The prevalence of advanced chronic kidney disease (CKD) is higher in Black than in White Americans. We evaluated CKD progression in Black and White participants and the contribution of biological risk factors. We included the study of lung function (measured by forced vital capacity [FVC]), which is part of the emerging notion of interorgan cross-talk with the kidneys to racial differences in CKD progression. This longitudinal study included 2175 Black and 2207 White adult Coronary Artery Risk Development in Young Adults (CARDIA) participants. Estimated glomerular filtration rate (eGFR) and urinary albumin-to-creatinine ratio (UACR) were measured at study year 10 (age 27-41y) and every five years for 20 years. The outcome was CKD progression through no CKD, low, moderate, high, or very high-risk categories based on eGFR and UACR in combination. The association between race and CKD progression as well as the contribution of risk factors to racial differences were assessed in multivariable-adjusted Cox models. Black participants had higher CKD transition probabilities than White participants and more prevalent risk factors during the 20-year period studied. Hazard ratios for CKD transition for Black (vs White participants) were 1.38 from No CKD into ≥ low risk, 2.25 from ≤ low risk into ≥ moderate risk, and 4.49 from ≤ moderate risk into ≥ high risk. Racial differences in CKD progression from No CKD into ≥ low risk were primarily explained by FVC (54.8%), hypertension (30.9%), and obesity (20.8%). In contrast, racial differences were less explained in more severe transitions. Black participants had a higher risk of CKD progression, and this discrepancy may be partly explained by FVC and conventional risk factors.


Effects of diversity and procrastination in priority queuing theory: the different power law regimes.
Empirical analyses show that after the update of a browser, or the publication of the vulnerability of a software, or the discovery of a cyber worm, the fraction of computers still using the older browser or software version, or not yet patched, or exhibiting worm activity decays as a power law approximately 1/t(alpha) with 0<alpha<or=1 over a time scale of years. We present a simple model for this persistence phenomenon, framed within the standard priority queuing theory, of a target task which has the lowest priority compared to all other tasks that flow on the computer of an individual. We identify a "time deficit" control parameter beta and a bifurcation to a regime where there is a nonzero probability for the target task to never be completed. The distribution of waiting time T until the completion of the target task has the power law tail approximately 1/t(1/2), resulting from a first-passage solution of an equivalent Wiener process. Taking into account a diversity of time deficit parameters in a population of individuals, the power law tail is changed into 1/t(alpha), with alpha is an element of (0.5,infinity), including the well-known case 1/t. We also study the effect of "procrastination," defined as the situation in which the target task may be postponed or delayed even after the individual has solved all other pending tasks. This regime provides an explanation for even slower apparent decay and longer persistence.


[Group A bovine rotavirus: diagnosis and antigenic characterization of strains circulating in the Argentine Republic, 1994-1999].
Group A Bovine Rotavirus (BRV) has been identified as a major cause of neonatal diarrhea in cattle. The study was aimed to determine the prevalence of BRV and to antigenically characterize the G-types of circulating strains in dairy and beef herds in Argentina. A total of 1129 stool samples from diarrheic calves was analyzed from 1994 to 1999. The samples were initially screened for RV by ELISA and PAGE, and then G-typed using monoclonal antibodies (Mab) directed against G1, G2, G3, G6 and G10-specific epitopes. Forty percent (452/1129) of the samples were positive for RV by ELISA, while 24.7% (279/1129) were also positive for PAGE. VP7 was detected in the 70.5% (319/452) of the positive samples using a broadly reactive Mab (C60); 32.6% (104/319) were G6, 15.4% (49/319) were G10, and 6% (19/319) were G1. However, 46.1% (147/319) of the samples remained untypable. Rotavirus diarrhea prevalences were comparable in beef and dairy herds (87.3% and a 74.4%, respectively). Finally, G6 was the most prevalent G-type circulating in beef herds while G10 prevailed in dairy herds. A better understanding of RV epidemiology will contribute to the optimization of current vaccines and prevention programs of RV diarrhea in calves.


[Epidemiological and clinicopathological characteristics of prostate cancer in Hunan].
To investigate the epidemiological and clinicopathological characteristics of PCa and provide some strategies for the clinical prevention and treatment of the malignancy. This study included 1 594 cases of pathologically diagnosed PCa after radical prostatectomy in Xiangya Hospital of Central South University from January 1, 2010 to December 31, 2020. We collected the basic information about the patients, their main complaints and clinicopathological results, and analyzed the epidemiological and clinicopathological data. The patients were aged from 28 to 93 years, and the number of PCa cases showed an overall upward trend from 2010 to 2020. Urinary system symptoms were most common (62.53%) as initial symptoms, followed by increased PSA (17.82%), PCa, prostate nodule, prostate mass (8.43%) and bone metastasis (2.94%) found at physical examinations, and the cases of PSA elevation among the clinic visitors increased year by year from 2010 to 2020. Gleason score 7 was found in a largest proportion of the PCa patients, and adenocarcinoma was the main pathological type (78.6%). Logistic regression analysis showed that high Gleason score, instead of age and expressions of Ki67, AR and ERG, was an independent risk factor for intraductal carcinoma. The incidence of PCa shows an increasing trend, and is more common in those over 50 years old. PSA screening is gradually popularized in China. Intraductal carcinoma, as a major risk factor for aggressive PCa and poor prognosis of the malignancy, is significantly correlated with high Gleason scores.


Male bovine GH transgenic mice have decreased adiposity with an adipose depot-specific increase in immune cell populations.
White adipose tissue (WAT) is composed of mature adipocytes and a stromal vascular fraction (SVF), which contains a variety of cells, including immune cells that vary among the different WAT depots. Growth hormone (GH) impacts immune function and adiposity in an adipose depot-specific manner. However, its effects on WAT immune cell populations remain unstudied. Bovine GH transgenic (bGH) mice are commonly used to study the in vivo effects of GH. These giant mice have an excess of GH action, impaired glucose metabolism, decreased adiposity, increased lean mass, and a shortened lifespan. Therefore, the purpose of this study was to characterize the WAT depot-specific differences in immune cell populations in the presence of excess GH in vivo. Three WAT depots were assessed: inguinal (sc), epididymal (EPI), and mesenteric (MES). Subcutaneous and MES bGH WAT depots showed a significantly higher number of total SVF cells, yet only MES bGH WAT had higher leukocyte counts compared with control samples. By means of flow cytometry analysis of the SVF, we detected greater macrophage and regulatory T-cell infiltration in sc and MES bGH WAT depots compared with controls. However, no differences were observed in the EPI WAT depot. RNA-sequencing confirmed significant alterations in pathways related to T-cell infiltration and activation in the sc depot with fewer significant changes in the EPI bGH WAT depot. These findings collectively point to a previously unrecognized role for GH in influencing the distribution of WAT immune cell populations in a depot-specific manner.


Cervical epidural hematoma: case report.
Cervical epidural hematoma is a rare phenomenon in children. MRI scan of the cervical spine is the method of choice in establishing diagnosis and a quick evacuation of hematoma and de- compression. We present a case of 11-year-old boy whose lower extremities were paralysed after a trivial injury of the cervical spine which he sustained while playing. Seven days after the injury, severe clinical symptoms appeared, and MRI of the spine showed the presence of cervical epidural hematoma. Cervical epidural hematoma in children is very rare. Adequate neurological examination, di- agnostics and urgent surgical intervention are of paramount importance for accomplishing good results. Early and persistent rehabilitation are the condition for achieving maximal recovery.


A tangled web: regulatory connections between quorum sensing and cyclic Di-GMP.
Bacteria sense and respond to environmental cues to control important developmental processes. Two widely conserved and important strategies that bacteria employ to sense changes in population density and local environmental conditions are quorum sensing (QS) and cyclic di-GMP (c-di-GMP) signaling, respectively. The importance of these pathways in controlling a broad variety of functions, including virulence, biofilm formation, and motility, has been recognized in many species. Recent research has shown that these pathways are intricately intertwined. Here we review the regulatory connections between QS and c-di-GMP signaling. We propose that the integration of QS with c-di-GMP allows bacteria to assimilate information about the local bacterial population density with other physicochemical environmental signals within the broader c-di-GMP signaling network.


[Secretory IgA of the cervical mucus in neoplastic and nonneoplastic conditions of the uterine cervix].
In 39 women affected by cervical intraepithelial neoplasia (CIN) concentration of the cervical mucus secretory IgA (sIgA) was significantly higher than in 414 controls matched for age, reproductive status and smoking habit (196 healthy women; 109 with "specific" and "aspecific" cervicitis or cervico-vaginitis; 51 with benign epithelial disorders of the cervix; 40 with adenomatous cervical polyp and 18 with early invasive exocervical squamous carcinoma). CIN carried the highest proportion of cases with sIgA detectable or beyond the cut-off value and sIgA concentration was inversely related to CIN grade. Present data confirm our preliminary investigation on the cervical total IgA and explain that any increased levels of these IgA are induced by the secretory and not serum fraction of this immunoglobulin. We still don't know the exact meaning and value of the present results. It is only possible to suppose that they are the expression of a vigorous local immune activation adverse to CIN, which is elevated for as long as the architecture of cervical glandular epithelia is preserved.


Getting Insights From Twitter: What People Want to Touch in Daily Life.
Understanding what people want to touch in daily life has been one of the central topics in the fields of haptic science, engineering, and marketing. Several studies have addressed the topic, however, their findings were highly dependent on the experimental stimuli in the laboratory environment. In this study, we tried to gain insights into targets that people want to touch in daily life by conducting a Twitter survey. We collected a considerable amount of Japanese Twitter posts containing references to the desire for touch. To capture the motivation underlying these desires in relation to haptic properties, we used several queries that comprehensively covered exploratory procedures. The results showed that targets that people wanted to touch depended on the exploratory procedures in the queries used (e.g., "want to stroke" tended to target people and animals). We also found that these targets were desirable to touch not only for their haptic properties but also as a means of communicating with other people or living animals. Our findings would be important for understanding human haptic function in the real world and for developing consumer haptic displays and applications.


Aging in binary-state models: The Threshold model for complex contagion.
We study the non-Markovian effects associated with aging for binary-state dynamics in complex networks. Aging is considered as the property of the agents to be less prone to change their state the longer they have been in the current state, which gives rise to heterogeneous activity patterns. In particular, we analyze aging in the Threshold model, which has been proposed to explain the process of adoption of new technologies. Our analytical approximations give a good description of extensive Monte Carlo simulations in Erdős-Rényi, random-regular and Barabási-Albert networks. While aging does not modify the cascade condition, it slows down the cascade dynamics towards the full-adoption state: the exponential increase of adopters in time from the original model is replaced by a stretched exponential or power law, depending on the aging mechanism. Under several approximations, we give analytical expressions for the cascade condition and for the exponents of the adopters' density growth laws. Beyond random networks, we also describe by Monte Carlo simulations the effects of aging for the Threshold model in a two-dimensional lattice.


Ocular manifestations of isolated corneal bee sting injury, management strategies, and clinical outcomes.
The purpose of this study is to describe the presenting features, management strategies, and clinical outcome following bee sting injury to the cornea. Retrospective case series involving 11 eyes of 11 patients with corneal bee sting injuries who presented over a period of 2 years. Nine of these 11 eyes had the presence of intact bee stinger in the cornea, which was removed immediately under an operating microscope and sent for microbiological and histopathological evaluation. The patients were managed as per the individual treatment protocol of the respective treating physicians. Six eyes (54.5%) had a good clinical outcome (best-corrected visual acuity [BCVA] >20/40) with medical therapy alone with no need for surgical intervention. Five eyes (45.5%) had a poor clinical outcome (BCVA <20/40) with medical therapy and required surgery; of which three required a combined penetrating keratoplasty with cataract surgery, while one required isolated cataract surgery and one underwent penetrating keratoplasty. Glaucoma was present in 3/5 eyes undergoing surgery, one of which required a trabeculectomy. Five of the six eyes who had a good clinical outcome with medical therapy alone had been treated with concomitant oral steroids, along with topical antibiotic-steroid combination therapy. Oral corticosteroid supplementation to the topical steroid antibiotic treatment in patients with corneal bee sting injury where corneal involvement and anterior reaction is severe at presentation or inflammation not ameliorating with topical steroids alone prevents serious vision-threatening complications such as corneal decompensation, cataract, and glaucoma.


Total Synthesis of (-)-N-Methylwelwitindolinone B Isothiocyanate.
The asymmetric synthesis of (-)-N-methylwelwitindolinone B isothiocyanate is reported. Critical challenges overcome through these studies include the stereoselective installation of the sterically congested C13 alkyl chloride and control of the wayward reactivity of the indole unit to standard oxidants. A Pt-catalyzed hydrosilylation helped stymie unwanted rearrangements facilitated by vinyl group participation during the chloride installation step, and a new FeII -catalyzed oxidation accomplished the problematic conversion of indole into 2-indolinone.


Chimeric receptor mRNA transfection as a tool to generate antineoplastic lymphocytes.
mRNA transfection is a useful approach for temporal cell reprogramming with minimal risk of transgene-mediated mutagenesis. We applied this to redirect lymphocyte cytotoxicity toward malignant cells. Using the chimeric immune receptor (CIR) constructs anti-CD19 CIR and 8H9 CIR, we achieved uniform expression of CIRs on virtually the entire population of lymphocytes. We reprogrammed CD3+ CD8+, CD3+ CD4+, and natural killer (NK ) cells toward autologous and allogeneic targets such as B cells, Daudi lymphoma, primary melanoma, breast ductal carcinoma, breast adenocarcinoma, and rhabdomyosarcoma. The reprogramming procedure is fast. Although most of the experiments were performed on lymphocytes obtained after 7-day activation, only 1-day activation of T cells with anti-CD3, anti-CD28 antibodies, and interleukin-2 is sufficient to develop both lymphocyte cytotoxicity and competence for mRNA transfer. The entire procedure, which includes lymphocyte activation and reprogramming, can be completed in 2 days. The efficiency of mRNA-modified human T cells was tested in a murine xenograft model. Human CD3+CD8+ lymphocytes expressing anti-CD19 CIR mRNA inhibited Daudi lymphoma growth in NOD=SCID mice. These results demonstrate that a mixed population of cytotoxic lymphocytes, including T cells together with NK cells, can be quickly and simultaneously reprogrammed by mRNA against autologous malignancies. With relatively minor modifications the described method of lymphocyte reprogramming can be scaled up for cancer therapy.


Efficient light harvesting by photosystem II requires an optimized protein packing density in Grana thylakoids.
A recently developed technique for dilution of the naturally high protein packing density in isolated grana membranes was applied to study the dependence of the light harvesting efficiency of photosystem (PS) II on macromolecular crowding. Slight dilution of the protein packing from 80% area fraction to the value found in intact grana thylakoids (70%) leads to an improved functionality of PSII (increased antenna size, enhanced connectivity between reaction centers). Further dilution induces a functional disconnection of light-harvesting complex (LHC) II from PSII. It is concluded that efficient light harvesting by PSII requires an optimal protein packing density in grana membranes that is close to 70%. We hypothesize that the decreased efficiency in overcrowded isolated grana thylakoids is caused by excited state quenching in LHCII, which has previously been correlated with neoxanthin distortion. Resonance Raman spectroscopy confirms this increase in neoxanthin distortion in overcrowded grana as compared with intact thylakoids. Furthermore, analysis of the changes in the antenna size in highly diluted membranes indicates a lipid-induced dissociation of up to two trimeric LHCII from PSII, leaving one trimer connected. This observation supports a hierarchy of LHCII-binding sites on PSII.


Facile Route to Tetrasubstituted Pyrazoles Utilizing Ceric Ammonium Nitrate.
A convenient approach for the synthesis of tetrasubstituted pyrazoles is described. The method involves the treatment of 1,3-diketones and allyltrimethylsilane with CAN followed by cerium-catalyzed addition of substituted hydrazines to construct pyrazoles in good yields.


Lipid nanoparticle-mediated delivery of IL-21-encoding mRNA induces viral clearance in mouse models of hepatitis B virus persistence.
Hepatitis B virus (HBV) covalently closed circular DNA (cccDNA), the transcription template for all viral mRNAs, is highly stable and current treatment options cannot effectively induce its clearance. Previously, we established an HBV persistence mouse model based on a clinical isolate (termed BPS) and identified interleukin-21 (IL-21) as a potent inducer of HBV clearance. Lipid nanoparticle (LNP) mediated delivery of mRNA has proven to be a highly safe and effective delivery platform. This work explored the applicability and effectiveness of the mRNA-LNP platform in IL-21-based HBV therapies. First, LNP-encapsulated murine IL-21 mRNA (LNP-IL-21) was prepared, characterized, and demonstrated to engender IL-21 expression in vitro and in vivo. Next, LNP-IL-21 was shown to induce clearance of both serum and intrahepatic HBV antigen and DNA in two HBV persistence mouse models based on BPS and recombinant cccDNA (rcccDNA), respectively, which was associated with HBV-specific humoral and cellular immune responses. Furthermore, peripheral blood mononuclear cells from BPS persistence mice treated ex vivo with LNP-IL-21 and HBV surface antigen (HBsAg) could induce similar HBV clearance upon infusion into recipient mice. These findings indicated that IL-21 combined with mRNA-LNP platform represents a valid and promising strategy for developing novel therapeutics against chronic HBV infection.


[Filtration of active fractions with hemostasis effect from platycladi cacumen carbonisatum].
To discuss the hemostasis of the different polarities of Platycladi Cacumen Carbonisatum (PCC) on the blood heat and hemorrhage syndrome rat model induced by dry yeast. The SD rats were divided into seven groups. Yunnan Baiyao was taken as the positive control drug. The rats in the control group and model group were fed with CMC-Na for 7 days, and the rats in other groups were fed with corresponding drugs simultaneously. On day 7, the blood heat and hemorrhage syndrome rat model was established. Indexes including the whole blood viscosity, plasma viscosity, thrombin time (TT), activated partial thromboplastin time (APTT), prothrombin time (PT), fibrinogen content (FIB), red blood cell (RBC), hemoglobin (HGB), hematocrit (HCT), blood platelet count (PLT), thrombocytocrit (PCT), mean platelet volume (MPV), platelet distribution width (PDW) and the rate of platelet aggregation induced by ADP were detected. Additionally, the pathological examinations of lungs among each group were compared. Compared with the control group, the RBC, HGB and HCT of rats in the model group increased significantly, with distinct increase in high, middle and low whole blood viscosity and plasma viscosity of rats in the model group; TT and APTT were notably prolonged, while PT was notably shortened, with significant increase in FIB content; PLT, PCT, MPV and PDW remarkably increased; Additionally, the rate of platelet aggregation induced by ADP significantly decreased. After ig administration of the ethyl acetate extract of PCC, the low whole blood viscosity and plasma viscosity remarkably decreased; TT and APTT were significantly shortened, with notable reduction in PDW and in FIB content Additionally, the rate of platelet aggregation induced by ADP significantly increased. The injury of lungs was also improved in ethyl acetate extract group. The rate of platelet aggregation induced by ADP of n-butanol extract group notablly increased. Plasma viscosity of water extract group remarkably decreased, with TT being significantly shortened. But the effects of n-butanol extract or water extract were weaker than that of ethyl acetate extract. And the effect of petroleum ether extract was the weakest. Ethyl acetate extract is the active part of PCC, showing the effect of hemostasis by reducing the low whole blood and plasma viscosity, improving coagulation function mainly by acting on the endogenous coagulation, and ameliorating the function of platelet aggregation.


Probing nanodispersions of clays for reactive foaming.
Nanodispersions of clays in polyurethane components have been prepared. Nanoclays (both natural and organically modified) of various aspect ratios are used. The fillers are dispersed separately in polyurethane components, viz., polyol and polyisocyanate. The nanodispersions are characterized by the combined use of solution rheology, X-ray scattering, cryo-electron microscopy, and IR spectroscopy. Reactive foaming of these nanodispersions is carried out to make polyurethane nanocomposite foams. The status of the dispersion of fillers in components and in foams has been compared to investigate the effect of the foaming process in exfoliation. Interpretation of the results from different characterization techniques describes the state of the dispersion of fillers in components and in foam. The rheological and physicochemical behaviors of nanodispersions are shown to have a significant influence on the properties of nanocomposite foams.


New directions in plasma exchange.
This review examines the literature published on therapeutic plasma exchange during 2002. The review was performed by searching Medline for pertinent articles. One hundred thirty articles were identified, of which 11 are reviewed. During the period, reviews of the use of therapeutic plasma exchange for managing Guillain-Barré syndrome and myasthenia gravis were published. A large randomized trial of the use of plasma exchange to treat sepsis also appeared. Finally, a large case series of the use of plasma exchange in Wegener granulomatosis was published. The literature confirms the use of plasma exchange for Guillain-Barré syndrome but suggests that inadequate evidence exists to support its use for long-term improvement in myasthenia gravis. The study of patients with severe sepsis suggests that plasma exchange may benefit a subset of patients, those with abdominal infections. Finally, plasma exchange for Wegener granulomatosis with severe renal dysfunction appears not to offer any benefit over immunosuppressive therapy.


Lessons from severe acute respiratory syndrome (SARS): implications for infection control.
Severe acute respiratory syndrome (SARS), the first global epidemic in the 21st century, affected over 8500 people in approximately 30 countries . With a crude mortality of 9%, its cause was quickly identified as a novel coronavirus that jumped species from animals to man. The SARS coronavirus epidemic, which began in the Fall of 2002, was related to the exotic food industry in southern China, initially involving disproportionate numbers of animal handlers, chefs, and caterers. Subsequently, person-to-person transmission spawned the outbreak. What distinguished this illness clinically was the fact that approximately half of the victims were health care workers , infected while caring for recognized or unrecognized patients with SARS. There are many curiosities and uncertainties surrounding the epidemic of SARS with lessons that may be useful to the community of infectious diseases physicians, especially when looking ahead to the next epidemic. Herein we relate our perspectives on useful lessons derived from a review of the SARS epidemic.


Engineering large animal models of human disease.
The recent development of gene editing tools and methodology for use in livestock enables the production of new animal disease models. These tools facilitate site-specific mutation of the genome, allowing animals carrying known human disease mutations to be produced. In this review, we describe the various gene editing tools and how they can be used for a range of large animal models of diseases. This genomic technology is in its infancy but the expectation is that through the use of gene editing tools we will see a dramatic increase in animal model resources available for both the study of human disease and the translation of this knowledge into the clinic. Comparative pathology will be central to the productive use of these animal models and the successful translation of new therapeutic strategies.


[Research in use of vascular endothelial cells to promote osteogenesis of marrow stromal cells].
Osteogenesis deep in the materials is postponed because the blood vessels grow into the materials very slowly. It is one of the key challenges to the bone tissue engineering researchers. However, it was found that marrow stromal cells can produce vascular endothelial growth factor (VEGF) while endothelial cells produce bone morphogenetic protein (BMP). So we presume if we have co-culture of marrow stromal cells and endothelial cells on the biomaterials, osteogenesis and angiogenesis may be promoted simultaneously. In this experiment, we compare the alkaline phosphatase (ALP) activity and osteocalcin (OCN) production of three groups: the marrow stromal cells under activation of endothelial cells culture fluid, the induced marrow stromal cells, and the untreated marrow stromal cells. The results reveal that the ALP activity and OCN production of the marrow stromal cells under activation of endothelial cell culture fluid and the ALP activity and OCN production of the induced marrow stromal cells do not show statistically significant difference, but they are significantly higher than those of the untreated marrow stromal cells (P < 0.01). It is concluded that the VEGF in the endothelial cell culture fluid can promote osteogenesis as effective as osteogenic induction medium can do.


Functionalization of Polyethylene (PE) and Polypropylene (PP) Material Using Chitosan Nanoparticles with Incorporated Resveratrol as Potential Active Packaging.
The present paper reports a novel method to improve the properties of polyethylene (PE) and polypropylene (PP) polymer foils suitable for applications in food packaging. It relates to the adsorption of chitosan-colloidal systems onto untreated and oxygen plasma-treated foil surfaces. It is hypothesized that the first coated layer of chitosan macromolecular solution enables excellent antibacterial properties, while the second (uppermost) layer contains a network of polyphenol resveratrol, embedded into chitosan nanoparticles, which enables antioxidant and antimicrobial properties simultaneously. X-ray photon spectroscopy (XPS) and infrared spectroscopy (FTIR) showed successful binding of both coatings onto foils as confirmed by gravimetric method. In addition, both attached layers (chitosan macromolecular solution and dispersion of chitosan nanoparticles with incorporated resveratrol) onto foils reduced oxygen permeability and wetting contact angle of foils; the latter indicates good anti-fog foil properties. Reduction of both oxygen permeability and wetting contact angle is more pronounced when foils are previously activated by O2 plasma. Moreover, oxygen plasma treatment improves stability and adhesion of chitosan structured adsorbates onto PP and PE foils. Foils also exhibit over 90% reduction of Staphylococcus aureus and over 77% reduction of Escherichia coli as compared to untreated foils and increase antioxidant activity for over a factor of 10. The present method may be useful in different packaging applications such as food (meat, vegetables, dairy, and bakery products) and pharmaceutical packaging, where such properties of foils are desired.


Genotype-Phenotype of Isolated Foveal Hypoplasia in a Large Cohort: Minor Iris Changes as an Indicator of PAX6 Involvement.
Foveal hypoplasia (FVH) is defined as the lack of fovea with a relatively preserved neuroretina, occurring either as an isolated FVH (IFVH) condition or associated with other diseases. This study aimed to systemically molecularly characterize IFVH. Genetic defects in 33 families with IFVH were analyzed by exome sequencing. Variants in three genes (PAX6, SLC38A8, and AHR) were selected and evaluated with multistep bioinformatic tools. Mutations in the three genes were identified in 69.7% (23/33) of families with IFVH and infantile nystagmus, including 18 families with PAX6 mutations, 5 with SLC38A8 mutations, but none with AHR mutations. Clinical data from 32 patients in the 23 families showed FVH, infantile nystagmus, and full iris. Careful follow-up visits revealed subtle changes in iris in 9 of 14 patients with PAX6 variants. The PAX6 variants of the 18 families (15 missense and one stop-loss) were mostly located in the C-terminal region of the paired box domain. Variants in AHR, SLC38A8, and PAX6 contributed to IFVH in one (2%), 25 (45%), and 30 (53%) families with identified genetic defects (23 families in this study and 33 reported previously), respectively. PAX6 and SLC38A8 mutations are the main cause of IFVH based on our data and a systematic review. IFVH-associated PAX6 variants are mostly missense with a specific location, indicating a specific correlation of these variants with IFVH but not with typical aniridia. Full iris with subtle structural abnormalities is more common in patients with PAX6-associated IFVH, suggesting a potential diagnostic indicator.


Revisiting the genomic hypomethylation hypothesis of aging.
The genomic hypomethylation hypothesis of aging proposes that an overall decrease in global DNA methylation occurs with age, and it has been argued that the decrease in global DNA methylation could be an important factor in aging, resulting in the relaxation of gene expression regulation and abnormal gene expression. Since it was initially observed that DNA methylation decreased with age in 1974, 16 articles have been published describing the effect of age on global DNA methylation in various tissues from rodents and humans. We critically reviewed the publications on the effect of age on DNA methylation and the expression of the enzymes involved in DNA methylation to evaluate the validity of the hypomethylation hypothesis of aging. On the basis of the current scientific literature, we conclude that a decrease in the global methylation of the genome occurs in most if not all tissues/cells as an animal ages. However, age-related changes in DNA methylation in specific regions or at specific sites in the genome occur even though the global DNA methylation does not change.


Septic arthritis of the knee by Salmonella montevideo.
We describe a case of salmonella septic arthritis of the knee in a middle-aged woman with the following predisposing conditions: long-term corticosteroids and microscopic collagenous colitis. The patient presented with enteritis caused by the same strain 3 months before the arthritis. The first series of cultures were negative and the possibility of a chronic carriage of the disease was not suspected initially. The patient was treated with antibiotics and arthroscopic washouts; the corticosteroid treatment was maintained. There was a progressive clinical and microbiological improvement and the patient was discharged 3 weeks later. Salmonella montevideo is a rare form of salmonella and is known to be associated with tropical fishes, reptiles and imported species.


Preliminary study on diagnostic reference levels of whole-body PET-CT examinations in Jiangsu Province, China.
To survey the whole-body positron emission tomography/computed tomography (PET-CT) examinations in Jiangsu Province and establish the diagnostic reference levels (DRL). A total of nine hospitals in southern, central and northern Jiangsu Provinces were selected. Activity duration product (ADP), activity per body weight (AW), dose-length product (DLP) and total effective dose (ET) were choosen to establish DRLs for whole-body PET-CT examinations. DRL and achievable dose (AD) were calculated according to International Commission on Radiological Protection report. The conversion coefficient method was used to calculate the ET induced by PET-CT whole-body imaging. DRLs of whole-body PET-CT examinations in Jiangsu Province were set to be 922 mGy·cm (DLP), 4453 MBq.min (ADP), 5.22 MBq.kg-1(AW), 19.8 mSv (ET). The ET for whole-body PET-CT examinations is higher than other countries. The effective dose from radionuclides (EF) in female patients is lower than that in male patients. Effective doses from CT(ECT), ET and ECT/ET in female patients are higher than that in male patients (P < 0.01). Provincial DRLs are established for four radiation metrics in whole-body PET-CT examinations. DRL of AW in whole-body PET-CT examinations is at the medium level, and DLP is higher than that reported in most literature, which has the potential to be further reduced.


Diversity of the bacterial community in the rice rhizosphere managed under conventional and no-tillage practices.
Bacterial diversity in the rice rhizosphere at different rice growth stages, managed under conventional and no-tillage practices, was explored using a culture-based approach. Actinobacteria are among the bacterial phyla abundant in the rice rhizosphere. Their diversity was further examined by constructing metagenomic libraries based on the 16S rRNA gene, using actinobacterial- and streptomycete-specific polymerase chain reaction (PCR) primers. The study included 132 culturable strains and 125 clones from the 16S rRNA gene libraries. In conventional tillage, there were 38% Proteobacteria, 22% Actinobacteria, 33% Firmicutes, 5% Bacteroidetes, and 2% Acidobacteria, whereas with no-tillage management there were 63% Proteobacteria, 24% Actinobacteria, 6% Firmicutes, and 8% Bacteroidetes as estimated using the culture-dependent method during the four stages of rice cultivation. Principal coordinates analysis was used to cluster the bacterial communities along axes of maximal variance. The different growth stages of rice appeared to influence the rhizosphere bacterial profile for both cultivation practices. Novel clones with low similarities (89-97%) to Actinobacteria and Streptomyces were retrieved from both rice fields by screening the 16S rRNA gene libraries using actinobacterial- and streptomycete-specific primers. By comparing the actinobacterial community retrieved by culture-dependent and molecular methods, it was clear that a more comprehensive assessment of microbial diversity in the rice rhizosphere can be obtained using a combination of both techniques than by using either method alone. We also succeeded in culturing a number of bacteria that were previously described as unculturable. These were in a phylogenetically deep lineage when compared with related cultivable genera.


Expression of an enzymatically active Yb3 glutathione S-transferase in Escherichia coli and identification of its natural form in rat brain.
Glutathione S-transferases containing Yb3 subunits are relatively uncommon forms that are expressed in a tissue-specific manner and have not been identified unequivocally or characterized. A cDNA clone containing the entire coding sequence of Yb3 glutathione S-transferase mRNA was incorporated into a pIN-III expression vector used to transform Escherichia coli. A fusion Yb3-protein containing 14 additional amino acid residues at its N terminus was purified to homogeneity. Recombinant Yb3 was enzymatically active with both 1-chloro-2,4-dinitrobenzene and 1,2-dichloro-4-nitrobenzene as substrates but lacked glutathione peroxidase activity. Substrate specificity patterns of recombinant Yb3 were more limited than those of glutathione S-transferase isoenzymes containing Yb1- or Yb2-type subunits. Peptides corresponding to unique amino acid sequences of Yb3 as well as a peptide from a region of homology with Yb1 and Yb2 subunits were synthesized. These synthetic peptides were used to raise antibodies specific to Yb3 and others that cross-reacted with all Yb forms. Immunoblotting was utilized to identify the natural counterpart of recombinant Yb3 among rat glutathione transferases. Brain and testis glutathione S-transferases were rich in Yb3 subunits, but very little was found in liver or kidney. Physical properties, substrate specificities, and binding patterns of the recombinant protein paralleled properties of the natural isoenzyme isolated from brain.


Corynosoma acanthocephalans in their paratenic fish hosts in the northern Baltic Sea.
Cystacanth stages of three Corynosoma (Acanthocephala) species, C. strumosum and C. semerme, and a new species in the Bothnian Bay, C. magdaleni, were studied in the fourhorn sculpin (Myoxocephalus quadricornis) in 1996-1997. The length of the trunk and proboscis differentiated the three species in the fish. The stability of the Corynosoma infection was studied by comparing the present results with those collected from the same areas (central and coastal) in 1977-1982 (Valtonen, 1983a). As C. magdaleni and C. strumosum were not separated at that time, the joint infections of these two species (called "C. strumosum") were compared. The stability of infection with C. semerme in the central Bothnian Bay was noticeable (prevalences were 82.9 in earlier period and 81.9% in later period), while the prevalences of "C. strumosum" in the same areas had decreased (21 and 13.5%, respectively). This is suggested to be due to the disappearance of the marine bull-rout, Myoxocephalus scorpius, from the Bothnian Bay during the 1990s due to an overall decline in salinity throughout the Baltic Sea. In the coastal area Corynosoma infection was clearly lower than in central area in both periods.


An ultrasensitive biological probe enhanced RT-IPCR assay for detecting benzo[a]pyrene in environmental samples based on the specific polyclonal antibody.
Benzo[a]pyrene (BaP), a type of polycyclic aromatic hydrocarbon, is widely distributed in the environment. In this study, BaP immunogen and coating antigen were respectively prepared by different methods, and the specific antibody targeting the BaP analyte was obtained. Moreover, gold nanoparticles modified with the specific polyclonal antibody and thiol-capped DNA were prepared as biological probes. Based on the work above, an ultrasensitive biological probe enhanced real-time immuno-polymerase chain reaction (BP-rt-iPCR) assay was developed to detect BaP in several environmental samples. Under optimal conditions, the proposed method was used to detect BaP with a linearity ranging from 5 pg/l to 50 ng/l. The limit of detection was 1.63 pg/l. The recovery rates of the spiked samples ranged from 92.12% to 109.76% and the coefficients of variation were 7.53%-11.06%. This immunoassay was successfully used to detect BaP in environmental samples, and the BaP detection results were consistent with those obtained using high performance liquid chromatography, indicating that the BP-rt-iPCR method is accurate and reliable, and has great potential to detect trace amounts of BaP.


Essential Components of Educational Programs on Biomedical Writing, Editing, and Publishing.
The primary objective of educational programs on biomedical writing, editing, and publishing is to nurture ethical skills among local and international researchers and editors from diverse professional backgrounds. The mechanics, essential components, and target outcomes of these programs are described in this article. The mechanics covers the objectives, design, benefits, duration, participants and qualifications, program formats, administrative issues, and mentorship. The essential components consist of three core schedules: Schedule I Basic aspects of biomedical writing, editing, and communications; Schedule II Essential skills in biomedical writing, editing, and publishing; and Schedule III Interactive lectures on relevant topics. The target outcomes of the programs comprise knowledge acquisition, skills development, paper write-up, and journal publication. These programs add to the prestige and academic standing of the host institutions.


Gene expression profile of endotoxin-stimulated leukocytes of the term new born: control of cytokine gene expression by interleukin-10.
Increasing evidence now supports the association between the fetal inflammatory response syndrome (FIRS) with the pathogenesis of preterm labor, intraventricular hemorrhage and bronchopulmonary dysplasia. Polymorphonuclear leukocyte (PMNs) and mononuclear cell (MONOs) infiltration of the placenta is associated with these disorders. The aim of this study was to reveal cell-specific differences in gene expression and cytokine release in response to endotoxin that would elucidate inflammatory control mechanisms in the newly born. PMNs and MONOs were separately isolated from the same cord blood sample. A genome-wide microarray screened for gene expression and related pathways at 4 h of LPS stimulation (n = 5). RT-qPCR and ELISA were performed for selected cytokines at 4 h and 18 h of LPS stimulation. Compared to PMNs, MONOs had a greater diversity and more robust gene expression that included pro-inflammatory (PI) cytokines, chemokines and growth factors at 4 h. Only MONOs had genes changing expression (all up regulated including interleukin-10) that were clustered in the JAK/STAT pathway. Pre-incubation with IL-10 antibody, for LPS-stimulated MONOs, led to up regulated PI and IL-10 gene expression and release of PI cytokines after 4 h. The present study suggests a dominant role of MONO gene expression in control of the fetal inflammatory response syndrome at 4 hrs of LPS stimulation. LPS-stimulated MONOs but not PMNs of the newborn have the ability to inhibit PI cytokine gene expression by latent IL-10 release.


Staff and administration perspectives in a one-year geriatric rehabilitation developmental process.
A health care reform for senior citizens took effect in 1992 in Sweden. Shortcomings as regards geriatric rehabilitation were identified and, in 1995, governmental grants were assigned to local developmental projects. The aim of this study was to report the staff and administration perspectives in a geriatric rehabilitation developmental process over a 1-year period. In all, 782 staff and 45 administration respondents took part. The investigation was based on questionnaires and series of interviews. Significant positive changes with respect to collaboration between the authorities involved were demonstrated at the administrative level, while the most positive results at staff level concerned competence development in the group of employees without college education. A positive process as regards geriatric rehabilitation has started in the study district, indicating that governmental grants assigned for the stimulation of developmental activities are beneficial. Official goals for geriatric rehabilitation, points of departure for the organization of rehabilitation services and the content of general and specialized rehabilitation programmes are pinpointed as some of the areas deserving further attention.


Perioperative Increase in Neutrophil CD64 Expression is an Indicator for Intra-abdominal Infection after Colorectal Cancer Surgery.
Colorectal surgery is associated with a high incidence of postoperative infections. Early clinical signs are difficult to distinguish from the systemic inflammatory response related to surgical trauma. Timely diagnosis may significantly improve the outcome. The objective of this study was to compare a new biomarker index CD64 for neutrophils (iCD64n) with standard biomarkers, white blood cell (WBC) count, neutrophil/lymphocyte ratio (NLR), C-reactive protein (CRP) and procalcitonin (PCT) for the early detection of postoperative infection. The prospective study included 200 consecutive patients with elective colorectal cancer surgery. Postoperative values of biomarkers from the postoperative day (POD) 1 to POD5 were analysed by the receiver operating characteristic (ROC) analysis to predict infection. The Cox regression model and the Kaplan-Meier method were used to assess prognostic factors and survival. The increase of index CD64n (iCD64n) after surgery, expressed as the ratio iCD64n after/before surgery was a better predictor of infection than its absolute value. The best 30-day predictors of all infections were CRP on POD4 (AUC 0.72, 99% CI 0.61-0.83) and NLR on POD5 (AUC 0.69, 99% CI 0.57-0.80). The best 15-day predictors of organ/space surgical site infection (SSI) were the ratio iCD64n on POD1 (AUC 0.72, 99% CI 0.58-0.86), POD3 (AUC 0.73, 99% CI 0.59-0.87) and CRP on POD3 (AUC 0.72, 99% CI 0.57-0.86), POD4 (AUC 0.79, 99% CI 0.64-0.93). In a multivariate analysis independent risk factors for infections were duration of surgery and perioperative transfusion while the infection itself was identified as a risk factor for a worse long-term survival. The ratio iCD64n on POD1 is the best early predictor of intra-abdominal infection after colorectal cancer surgery. CRP predicts the infection with the same predictive value on POD3.


Effects of Healthy Aging and Mild Cognitive Impairment on a Real-Life Decision-Making Task.
In this study, we investigated the effects of age and of mild cognitive impairment (MCI) on decision making under risk by adopting a task representing real-life health-related situations and involving complex numerical information. Moreover, we assessed the relationship of real-life decision making to other cognitive functions such as number processing, executive functions, language, memory, and attention. For this reason, we compared the performance of 19 healthy, relatively younger adults with that of 18 healthy older adults and the performance of the 18 healthy older adults with that of 17 patients with MCI. Results indicated difficulties in real-life decision making for the healthy older adults compared with the healthy, relatively younger adults. Difficulties of patients with MCI relative to the healthy older adults arose in particular in difficult items requiring processing of frequencies and fractions. Significant effects of age and of MCI in processing frequencies were also evident in a ratio number comparison task. Decision-making performance of healthy participants and of the patient group correlated significantly with number processing. There was a further significant correlation with executive functions for the healthy participants and with reading comprehension for the patients. Our results suggest that healthy older individuals and patients with MCI make less advantageous decisions when the information is complex and high demands are put on executive functions and numerical abilities. Moreover, we show that executive functions and numerical abilities are not only essential in laboratory gambling tasks but also in more realistic and ecological decision situations within the health context.


Evaluation of monitoring sites for protection of groundwater in an urban area.
Monitoring for seasonal variation and changes in groundwater is a costly project. Assessing groundwater at selected monitoring sites and for site-specific indicators may reduce the cost of subsequent monitoring. In this context, the present study developed a method to assess groundwater using a combination of multivariate and univariate statistical techniques to identify critical sites of contamination. The sample data used describes the groundwater quality in Allahabad, India. The factor analysis brings out the observable parameters for groundwater pollution. Finally, univariate techniques such as analysis of variance (ANOVA) and Bonferroni t-test identify the critical sites of groundwater pollution. The first factor indicated high loading (>0.6) of total dissolved solids, Cl, Na, Mg, conductivity, SO4, and hardness. This represented overall pollution status of groundwater from human habitation, waste disposal, and agricultural activities in Allahabad. Iron, Mn, and Zn showed loading on distinct factors and indicated local contamination. Univariate techniques ANOVA and Bonferroni t-test for Zn concentration in handpump samples revealed heavy metal contamination at Hasimpur and Beniganj in India. Thus, initial monitoring followed by statistical analysis can help identify critical sampling locations and important indicators.


Presentation and management of pseudoaneurysms of femoral artery.
This study reports our experience of presentation, diagnosis and management of femoral pseudoaneurysms (PSAs). Descriptive study. This study was carried out at South Surgical Unit, Mayo Hospital, Lahore over a 3-year period from January 2001 to December 2003. Data was collected noting patient's demographic characteristics, etiology of aneurysms, modes of presentation, management and outcome. Thirteen patients presented with femoral artery PSAs. All except 2 were young males. Nine patients had aneurysms following IV drug abuse. Three occurred following accidental trauma and one followed angiography access. Ten presented with overt external bleeding (leaking) while 3 had closed rupture. Two PSAs were initially mistaken as an abscess and incised resulting in sudden hemorrhage. All IV drug abusers (n=9) had initial proximal / distal ligation to stop bleeding. Five had no further symptoms of ischemia, one had mild claudication, one developed rest pain and had had extra-anatomical ileo-popliteal bypass through the obturator foramen. One further patient had crossover femoral grafting because of critical ischemia. Four non-infected cases were reconstructed using direct repair, 2 reversed vein grafts and one polytetrafluoroethylene (PTFE) graft respectively. One patient (11%) each had a major and a minor limb amputation respectively. One patient left against medical advice after proximal /distal ligation. There was no mortality. There was one documented instance of recurrent drug abuse of PTFE graft. Femoral PSAs in our study was mostly due to IV drug abuse. All PSAs were either leaking or had frankly ruptured on presentation. If significant ischemia develops on ligation, bypass through the obturator foramen, placing the graft in depth away from recurrent abuse, is a useful option. These patients also need dedicated psychiatric rehabilitation to prevent further IV drug abuse.


Impact of sustained virologic response on chronic kidney disease progression in hepatitis C.
To determine how sustained virological response at 12 wk (SVR12) with direct acting antivirals (DAAs) for the treatment of hepatitis C virus (HCV) infection affects chronic kidney disease (CKD) progression. A retrospective analysis was performed in patients aged ≥ 18 years treated for HCV with DAAs at the VA Greater Los Angeles Healthcare System from 2014-2016. The treatment group was compared to patients with HCV from 2011-2013 who did not undergo HCV treatment, prior to the introduction of DAAs; the control group was matched to the study group in terms of age, gender, and ethnicity. Analysis of variance and co-variance was performed to compare means between SVR12 subgroups adjusting for co-variates. Five hundred and twenty-three patients were evaluated. When comparing the rate of change in estimated glomerular filtration rate (eGFR) one-year after HCV treatment to one-year before treatment, patients who achieved SVR12 had a decline in GFR of 3.1 mL/min ± 0.75 mL/min per 1.73 m2 compared to a decline in eGFR of 11.0 mL/min ± 2.81 mL/min per 1.73 m2 in patients who did not achieve SVR12 (P = 0.002). There were no significant clinical differences between patients who achieved SVR12 compared to those who did not in terms of cirrhosis, treatment course, treatment experience, CKD stage prior to treatment, diuretic use or other co-morbidities. The decline in eGFR in those with untreated HCV over 2 years was 2.8 mL/min ± 1.0 mL/min per 1.73 m2, which was not significantly different from the eGFR decline noted in HCV-treated patients who achieved SVR12 (P = 0.43). Patients who achieve SVR12 have a lesser decline in renal function, but viral eradication in itself may not be associated improvement in renal disease progression.


Deletion of amino acids Asp487-Ser488-Phe489 in human cytochrome P450c17 causes severe 17 alpha-hydroxylase deficiency.
17 alpha-Hydroxylase deficiency blocks the biosynthesis of cortisol and sex steroids, resulting in mineralocorticoid excess, hypertension, sexual infantilism, and female phenotype in both genetic sexes. The disease is caused by mutations in the gene encoding cytochrome P450c17, which is the single enzyme that mediates both 17 alpha-hydroxylase and 17,20-lyase activities. We report a 14-yr-old patient from Thailand with a classical clinical presentation of this rare disorder. Analysis of her P450c17 gene by polymerase chain reaction amplification and sequencing showed a nine-base deletion, eliminating codons 487-489 (Asp-Ser-Phe) near the carboxy-terminus of P450c17. This deletion creates a BclI site in the mutant DNA, permitting accurate demonstration that the patient was homozygous for this lesion, whereas one parent and two siblings were heterozygous. By use of site-directed mutagenesis, we created a vector that could express this mutated form of P450c17 when transfected into non-steroidogenic COS-1 cells. Such transfected cells produced immunodetectable P450c17 protein, but had no 17 alpha-hydroxylase or 17,20-lyase activity, whereas cells similarly transfected with a vector expressing normal human P450c17 could 17 alpha-hydroxylate either pregnenolone or progesterone and convert 17 alpha-hydroxypregnenolone to dehydroepiandrosterone, showing the presence of both activities. This is the first report of the molecular genetic basis of 17 alpha-hydroxylase deficiency in a Southeast Asian patient.


Modification of low density lipoprotein association with the arterial intima. A possible environment for the antiatherogenic action of beta-blockers.
The accumulation of lipoproteins and lipids associated with the progression of atherosclerotic lesions appears to be a sequential process involving interactions with the intimal extracellular matrix and, subsequently, with cells. Apolipoprotein B-containing lipoproteins appear first to be retained and modified focally by proteoglycans of the extracellular matrix. The association with the extracellular matrix may lead to further modifications. In vitro resident macrophages take up the modified apolipoprotein B lipoproteins via a nonsaturable mechanism that may contribute to their transformation into foam cells characteristic of the atherosclerotic lesion. The affinity of low density lipoprotein (LDL) for arterial proteoglycans in vitro is related to the charge and triglyceride content. Small, triglyceride-poor, cholesterol-rich particles interact more efficiently with proteoglycans and are taken up faster by cultured macrophages than larger triglyceride-rich ones. beta-Blockers increase the relative triglyceride content of circulating LDL, and in vitro this LDL has a lower affinity for arterial proteoglycans. These results suggest that some of the experimental antiatherogenic actions of beta-blockers may be related to a reduced LDL affinity for extracellular intima components associated with the small changes induced by the drugs in the lipoprotein structure. Hypothetically, this reduced affinity could diminish the focal accumulation of LDL in lesion-prone sites.


[The importance of clinical symptoms in the diagnosis of bacterial meningitis in neonates].
In a group of 32 neonates with bacterial meningitis (BM) the authors investigated the frequency of clinical symptoms and compared it with the frequency in a control group of 27 neonates where BM was ruled out. The following were significantly more frequent in neonates with BM: elevated temperature (p < 0.01) and seizures (p < 0.05). In the control group impaired muscular tonus was significantly more frequent (p < 0.05). Temperature had the highest diagnostic sensitivity (93.7%), followed by seizures (62.5%); exanthema had the highest specificity (92.6%), followed by bulging (92%). Neither sensitivity nor specificity of any of the investigated clinical symptoms reached the required level of 96%.


Whether Assisted Intramedullary Nail Implantation Without Traction Table is as Safe and Effective as Using Traction Table of Older Intertrochanteric Fracture Patients?
Despite promising clinical outcome proposals, there has been relatively little published regarding the use of traction table-assisted intramedullary nail implantation for intertrochanteric fractures. The purpose of this study is to further summarize and evaluate published clinical studies comparing the clinical outcomes of using traction table and without traction table in the management of intertrochanteric fracture. A comprehensive literature search using PubMed, Cochrane Library, and Embase was systematically performed to evaluate all studies included in the literature up to May 2022. The search terms included "intertrochanteric fractures", "hip fractures", and "traction table" with Boolean operators "AND" and "OR". The following information was extracted and summarized: demographic information, setup time, surgical time, amount of bleeding, fluoroscopy exposure time, reduction quality, and Harris Hip Score (HHS). A total of eight clinical controlled studies involving 620 patients were eligible for the review. The mean age at the time of injury was 75.3 years (traction table group 75.7 years, non-traction table group 74.9 years). The most common assisted intramedullary nail implantation method of non-traction table group included lateral decubitus position (4 studies), traction repositor, (3 studies) and manual traction (1 studies). Included studies results all support that there was no difference between the two groups in terms of reduction quality and Harris Hip Score, and the non-traction table group had an advantage in terms of setup time. However, there were still disputes in terms of surgical time, amount of bleeding and fluoroscopy exposure time. For patients with intertrochanteric fractures, assisting intramedullary nail implantation without traction table is as safe and effective as using traction table and doing so without a traction table may be more advantageous in terms of setup time.


Evidence for the absence of Staphylococcus aureus in land applied biosolids.
Staphylococcus aureus is an important human pathogen both within the hospital setting and as a community-acquired infection. Recently there has been concern that land applied biosolids may transmit S. aureus. However, no scientific data are available to document whether biosolids are a source of S. aureus. To determine if S. aureus is present in biosolids, we collected samples from 15 sites across the United States. Samples analyzed were as follows: 3 raw untreated sewage samples and 2 undigested primary sewage sludge samples; 23 different biosolid samples; and 27 aerosols obtained during biosolid land application (biosolid aerosols). Although S. aureus were detected in raw sewage samples, none were found in any of the treated biosolids nor in any biosolid aerosol samples. These results suggest that biosolids are not a likely source of S. aureus human exposure or infection.


[Shock-induced aggression and reactivity following raphe lesion in rats. Effects of physostigmine (author's transl)].
Shock-induced fighting behavior, flinch-jump thresholds and locomotor open-field activity were studied following dorsal and medial raphe lesions in rats. Attack scores were raised for low-intensity shocks (1 mA) only, whereas they remained unchanged for shocks of higher intensity (2 mA), as compared to controls. The jump threshold is decreased in raphe lesioned animals, but the flinch threshold is unchanged. Physostigmine (0,2-0,5 mg/kg) reduces the lesion-induced hyperreactivity: locomotor open-field activity is reduced to a greater extent than in the controls, and habituation to the open-field situation is restored. Doses of physostigmine (e.g. 0,2 mg/kg), that do not modify shock-induced aggression in controls, reduce aggression in lesioned animals to the level shown by controls for low-intensity shocks. In conclusion, shock-induced aggression is not directly dependent on a serotonergic brain mechanism. The behavioral changes observed are related to the hyperreactivity induced by raphe lesions. This hyperreactivity presumably results from a reduced activity of cholinergic brain mechanisms.


Neuroticism and pain catastrophizing aggravate response to pain in healthy adults: an experimental study.
The aim of this study was to investigate the association between neuroticism, pain catastrophizing, and experimentally induced pain threshold and pain tolerance in a healthy adult sample from two regions of the country of Croatia: the island of Korcula and city of Split. A total of 1,322 participants were enrolled from the Island of Korcula (n = 824) and the city of Split (n = 498). Participants completed a self-reported personality measure Eysenck Personality Questionnaire (EPQ) and pain catastrophizing questionnaire Pain Catastrophizing Scale (PCS), followed by a mechanical pain pressure threshold and tolerance test. We have explored the mediating role of catastrophizing in the relationship between neuroticism and pain intensity. The results showed that pain catastrophizing partially mediated the relationship between neuroticism and pain intensity, suggesting the importance of pain catastrophizing in increasing vulnerability to pain. The results also indicated gender-related differences, marked by the higher pain threshold and tolerance in men. This study adds to the understanding of the complex interplay between personality and pain, by providing a better understanding of such mechanisms in healthy adults.


Iron-Catalyzed Ortho C-H Methylation of Aromatics Bearing a Simple Carbonyl Group with Methylaluminum and Tridentate Phosphine Ligand.
Iron-catalyzed C-H functionalization of aromatics has attracted widespread attention from chemists in recent years, while the requirement of an elaborate directing group on the substrate has so far hampered the use of simple aromatic carbonyl compounds such as benzoic acid and ketones, much reducing its synthetic utility. We describe here a combination of a mildly reactive methylaluminum reagent and a new tridentate phosphine ligand for metal catalysis, 4-(bis(2-(diphenylphosphanyl)phenyl)phosphanyl)-N,N-dimethylaniline (Me2N-TP), that allows us to convert an ortho C-H bond to a C-CH3 bond in aromatics and heteroaromatics bearing simple carbonyl groups under mild oxidative conditions. The reaction is powerful enough to methylate all four ortho C-H bonds in benzophenone. The reaction tolerates a variety of functional groups, such as boronic ester, halide, sulfide, heterocycles, and enolizable ketones.


Effect of aminophylline on coronary reactive and functional hyperaemic response in conscious dogs.
This study was undertaken to determine whether adenosine release from myocardial cells plays a role in coronary reactive and functional vasomotion. Reactive hyperaemic blood flow responses to 10 s complete occlusions and 400 ms diastolic occlusions of the left circumflex coronary artery and to the vasomotor responses to the increased cardiac demand following ventricular extra-activation were examined in a chronic, heart-blocked dog preparation during a control period and following intravenous bolus administration of aminophylline (5 mg X kg-1). Aminophylline administration resulted in a 19% decrease in the blood flow debt repayment ratio of 10 s reactive hyperaemic responses compared with the control period. However, administration of aminophylline had no effect on the coronary vascular response to 400 ms diastolic occlusions or to ventricular extra-activations. These observations indicate that adenosine may play a role in the coronary vascular response to prolonged interventions but that other factors, as yet unidentified, may be implicated in the beat-to-beat regulation of coronary vascular resistance.


Clinical correlates of filarial infection in Haitian children: an association with interdigital lesions.
To assess clinical findings associated with Wuchereria bancrofti infection, 192 school children in a filariasis-endemic area of Haiti underwent physical and ultrasonographic examinations and testing for circulating filarial antigen (CFA). The CFA-positive children were more likely than CFA-negative children to have severe interdigital lesions (> or = 1 macerated lesion with involvement of > or = 4 toe web spaces) (P < 0.0001) and inguinal (P = 0.003) or crural (P = 0.004) lymph node pathology. In multivariate analysis, CFA positivity remained a significant predictor for severe interdigital lesions (P = 0.006) and inguinal lymph node pathology (P = 0.05). Ultrasound detected adult worms and lymphangectasia (diameter = 2.0-4.0 mm) in 11 (10.8%) CFA-positive children. Among CFA-positive children, ultrasonographic detection of adult worms was associated with inguinal (P = 0.01) and crural (P = 0.004) lymph node pathology and advanced pubertal stage (sexual maturity rating = 3-5) (P = 0.02). This is the first study to associate interdigital lesions with filarial infection in children.


[Expressions of hTERT, p53, c-erbB-2 and Bcl-2 in colonic adenocarcinoma mouse models with liver metastases: effects of classical traditional Chinese medicine prescriptions for promoting circulation and removing blood stasis].
To observe the effects of classical traditional Chinese medicine prescriptions that function to promote blood circulation and removing blood stasis on the metastatic behavior of malignant tumors, and explore the possible mechanisms of such effects. BALB/c mouse models of colonic adenocarcinoma with liver metastases were established by intrasplenic injection of colonic adenocarcinoma cells (CT26) to receive treatment with the three representative classical circulation-promoting and blood stasis-removing prescriptions of traditional Chinese medicine, namely Guizhifuling pills, Didang Tang and Danshenyin, respectively. The expressions of human telomerase reverse transcriptase (hTERT), p53, c-erbB-2 and Bcl-2 were detected in the mouse models with different treatments and in normal control mice. Tumor metastases of various degrees were observed in the mice after inoculation of the tumor cells. The expressions of hTERT, p53, c-erbB-2 and Bcl-2 in the models receiving treatment with either Didang Tang or Guizhifuling pills differed significantly from those of the untreated model group (P<0.05), whereas between Danshenyin group and the model group, only the expression of hTERT showed significant difference. Didang Tang and Guizhifuling pills can reduce the expressions of hTERT, p53, c- erbB-2 and Bcl-2, while Danshenyin can only reduce the expression of hTERT without similar effects on the other 3 oncogenes. Such inhibitory effects of the prescriptions on hTERT and the oncogenes might explain their actions to inhibit malignant tumor metastasis, which can be related to performance of the prescriptions in promoting circulation by removing blood stasis.


Radiation dose of nuclear medicine technicians performing PET/MR.
Since october 2015, PET/MR has been used extensively for clinical routine in the nuclear medicine department of the Pitié-Salpêtrière Hospital (Paris, France) with a throughput of 11 to 15 patients each day. While many studies have been conducted to investigate dose reduction strategies to patients with hybrid PET/MR devices, no study has focused on staff radiation safety. Knowing that patient positioning within the scanner takes longer in PET/MR than in PET/CT because of the placement of several local MR receive coils, a retrospective study was carried out to measure the radiation doses to nuclear medicine technologists from the patient. The analysis was conducted during one year on 1332 clinical PET/MR studies performed with the Signa PET/MR system (General Electric Healthcare) in our department. The whole-body exposure of the technologist staff was on average for all PET/MR exams10.3 ± 4 nSv per injected MBq of 18 F. When performing brain PET/MR exams only, the whole-body exposure was on average 8.7 ± 2 nSv per injected MBq of 18 F. Brain PET/MR provides lower radiation dose than whole-body examinations for cancer screening due to a lower injected activity (2 vs. 3 MBq kg-1) and shorter patient positioning (5 vs. 15 min). When starting PET/MR in a nuclear medicine department, an important step is to optimise patient positionning within the scanner to minimise radiation dose received by the technical staff from patients.


Neurocognitive insights into substance abuse.
Cognitive studies are revealing key aspects of how drug abusers monitor and respond to negative feedback differently from non-abusers, and in doing so are adding an important piece to the conceptual puzzle that must be solved to understand, treat, and prevent drug abuse. In this review, we bring together two quite different lines of research, one addressing the selection of gambles in a risky decision task, and the other focused on imaging neural systems related to the detection and processing of errors. We suggest that diminished behavioural control, which is a cardinal feature of drug abuse, may be linked to alterations in the psychological and neural mechanisms that detect error signals and which, in turn, lead to optimization of behavioural responses.


A simple technique to make faster laparoscopic running sutures.
The authors show a simple technique for laparoscopic running sutures. The running suture is locked at the starting point, passing the needle through a small loop previously created at the free end of the suture. It is then completed making three to four continuous interlocking loops at the ending point.


A minority stress--emotion regulation model of sexual compulsivity among highly sexually active gay and bisexual men.
Sexual compulsivity represents a significant public health concern among gay and bisexual men, given its co-occurrence with other mental health problems and HIV infection. The purpose of this study was to examine a model of sexual compulsivity based on minority stress theory and emotion regulation models of mental health among gay and bisexual men. Gay and bisexual men in New York City reporting at least nine past-90-day sexual partners (n = 374) completed measures of distal minority stressors (i.e., boyhood gender nonconformity and peer rejection, adulthood perceived discrimination), hypothesized proximal minority stress mediators (i.e., rejection sensitivity, internalized homonegativity), hypothesized universal mediators (i.e., emotion dysregulation, depression, and anxiety), and sexual compulsivity. The hypothesized model fit the data well (RMSEA = 0.05, CFI = 0.98, TLI = 0.95, SRMR = 0.03). Distal minority stress processes (e.g., adulthood discrimination) were generally found to confer risk for both proximal minority stressors (e.g., internalized homonegativity) and emotion dysregulation. Proximal minority stressors and emotion dysregulation, in turn, generally predicted sexual compulsivity both directly and indirectly through anxiety and depression. The final model suggests that gay-specific (e.g., internalized homonegativity) and universal (e.g., emotion dysregulation) processes represent potential treatment targets to attenuate the impact of minority stress on gay and bisexual men's sexual health. Tests of interventions that address these targets to treat sexual compulsivity among gay and bisexual men represent a promising future research endeavor.


Effects of four anticholinesterase-anticholinergic combinations and tracheal extubation on QTc interval of the ECG, heart rate and arterial pressure.
Imbalance in cardiac sympathetic tone causes prolongation of the QTc interval of the ECG. On the other hand, impairment of the parasympathetic control of the heart rate caused by anticholinesterase-anticholinergic combinations might also affect the cardiac sympathetic tone and hence the QTc interval of the ECG. The main purpose of the present study was to compare the effects of four anticholinesterase-anticholinergic combinations used for the antagonism of the neuromuscular block on the QTc interval of the ECG, heart rate and arterial pressure. Eighty-four ASA class I-II patients with a mean age of 32 to 37 yr undergoing otolaryngological surgery were randomly allocated to one of the following groups: neostigmine 40 microg/kg+glycopyrronium 8 microg/kg (Ne-Glyc), neostigmine 40 microg/kg+atropine 20 microg/kg (Ne-Atr), edrophonium 200 microg/kg+atropine 300 microg (Edr-Atr (1)), edrophonium 500 microg/kg+atropine 7 microg/kg (Edr-Atr (2)). QTc interval and heart rate were measured by a signal processing method based on an IBM/PC/xT-compatible microcomputer and arterial pressure with a sphygmomanometer at 1-min intervals up to 10 min after the injection of the drugs and immediately and 2 min after extubation. The ECG, lead II, was continuously recorded. Neuromuscular block was measured by a Datex relaxograph. In all groups, the most pronounced increase in both QTc interval, heart rate and arterial pressure occurred 1 min after the study drugs and immediately after extubation. In all groups, the mean QTc intervals at 1 and 2 min after the study drugs and after extubation were longer than the upper limit of the normal range (440 ms). Junctional rhythm occurred in 1 to 3 patients in all other groups with the exception of the Edr-Atr(1) group in which no cardiac arrhythmias occurred. At 1 min, the heart rate in the Ne-Atr group was at a significantly higher level than that in the Ne-Glyc group. From 3 to 6 min, the heart rate in the Edr-Atr(2) group and at 3 min in the Edr-Atr(1) group was at a lower level than the heart rate in the Ne-Glyc group. On the basis of the present results, anticholinesterase-anticholinergic combinations should be avoided in patients having a long QT interval syndrome or a prolonged QT interval from other causes. In addition, the cardiovascular stimulation caused by tracheal extubation should also be avoided in these patients.


Genomic analyses confirm close relatedness between Rhodococcus defluvii and Rhodococcus equi (Rhodococcus hoagii).
Rhodococcus defluvii strain Ca11(T) was isolated from a bioreactor involved in extensive phosphorus removal. We have sequenced the whole genome of this strain, and our comparative genomic and phylogenetic analyses confirm its close relatedness with Rhodococcus equi (Rhodococcus hoagii) strains, which share >80 % of the gene content. The R. equi virulence plasmid is absent though most of the chromosomal R. equi virulence-associated genes are present in R. defluvii Ca11(T). These data suggest that although R. defluvii is an environmental organism, it has the potential to colonize animal hosts.


Detection of mRNA expression patterns by nonradioactive in situ hybridization on histological sections of floral tissue.
Analysis of gene activity with high spatial resolution is a prerequisite for deciphering regulatory networks which underlie developmental programs. Over many years, in situ hybridization has become the gold standard for the identification of in vivo expression patterns of endogenous mRNAs. Nonetheless, the method has several limitations, and the detection of lowly expressed transcripts is still a challenge. Here, we present a robust protocol for sensitive analysis of expression patterns in inflorescence tissue of Arabidopsis thaliana. We describe how the samples are fixed, embedded, and sectioned in preparation for in situ hybridization, how RNA probes are prepared, and how hybridization and detection is carried out. While the described protocol is optimized for inflorescence meristems, it can possibly be used for other tissues as well.


Role of Protein Dimeric Interface in Allosteric Inhibition of N-Acetyl-Aspartate Hydrolysis by Human Aspartoacylase.
The results of molecular modeling suggest a mechanism of allosteric inhibition upon hydrolysis of N-acetyl-aspartate (NAA), one of the most abundant amino acid derivatives in brain, by human aspartoacylase (hAsp). Details of this reaction are important to suggest the practical ways to control the enzyme activity. Search for allosteric sites using the Allosite web server and SiteMap analysis allowed us to identify substrate binding pockets located at the interface between the subunits of the hAsp dimer molecule. Molecular docking of NAA to the pointed areas at the dimer interface predicted a specific site, in which the substrate molecule interacts with the Gly237, Arg233, Glu290, and Lys292 residues. Analysis of multiple long-scaled molecular dynamics trajectories (the total simulation time exceeded 1.5 μs) showed that binding of NAA to the identified allosteric site induced significant rigidity to the protein loops with the amino acid side chains forming gates to the enzyme active site. Application of the protein dynamical network algorithms showed that substantial reorganization of the signal propagation pathways of intersubunit communication in the dimer occurred upon allosteric NAA binding to the remote site. The modeling approaches provide an explanation to the observed decrease of the reaction rate of NAA hydrolysis by hAsp at high substrate concentrations.


Doppler-free saturated-absorption spectroscopy of CO2 at 4.3 microm by means of a distributed feedback quantum cascade laser.
We report the application of a cw distributed feedback quantum cascade laser to Lamb-dip spectroscopy of CO2 at 4.3 microm. With the laser operating in the free-running mode, we observed the sub-Doppler profile of the P(28) line of the (0,1(1),0)->(0,1(1),1) hot band by implementing a pump-probe scheme and using wavelength modulation spectroscopy for highly sensitive detection of saturated absorption signals. We investigated the main limitations to the observation of a narrow resonance, with particular attention to the effect of the laser current noise. We determined the intrinsic laser emission width, which was found to be approximately 3.4 MHz (FWHM) for an observation time of approximately 200 ms.


Non-thermal ablation of rabbit liver VX2 tumor by pulsed high intensity focused ultrasound with ultrasound contrast agent: Pathological characteristics.
To investigate the pathological characteristics of non-thermal damage induced by pulsed high intensity focused ultrasound (PHIFU) combined with ultrasound contrast agent (UCA), SonoVue (Bracco SpA, Milan, Italy) in rabbit liver VX2 tumor. Liver VX2 tumor models were established in 20 rabbits, which were divided randomly into PHIFU combined with ultrasound contrast agent group (PHIFU + UCA group) and sham group. In the PHIFU + UCA group, 0.2 mL of SonoVue was injected intravenously into the tumor, followed by ultrasound exposure of I(SP) 5900 W/cm(2). The rabbits were sacrificed one day after ultrasound exposure. Specimens of the exposed tumor tissues were obtained and observed pathologically under light microscope and transmission electron microscope. The remaining tumor tissues were sent for 2,3,5-Triphenyltetrazolium chloride (TTC) staining. Before TTC staining, tumor tissues in both the sham and the PHIFU + UCA groups resembled gray fish meat. After TTC staining, the tumor tissues were uniformly stained red, with a clear boundary between tumor tissue and normal tissue. Histological examination showed signs of tumor cell injury in PHIFU + UCA group, with cytoplasmic vacuoles of various sizes, chromatin margination and karyopyknosis. Electron microscopic examination revealed tumor cell volume reduction, karyopyknosis, chromatin margination, intercellular space widening, the presence of high electron-density apoptotic bodies and vacuoles in cytoplasm. The non-thermal effects of PHIFU combined with UCA can be used to ablate rabbit liver VX2 tumors.


Glucose uptake via SGLT-1 is stimulated by beta(2)-adrenoceptors in the ruminal epithelium of sheep.
Glucose absorption via the sodium glucose-linked transporter (SGLT)-1, decreases the glucose concentration in the ruminant forestomach and may ameliorate or prevent ruminal lactic acidosis. Because acidotic ruminants show increased sympathetic activity, the possibility of adrenergic modulation of SGLT-1 was investigated. Glucose uptake into ovine ruminal epithelia was measured in Ussing chambers after the addition of 200 micromol/L (14)C-labeled glucose to the mucosal solution. Glucose uptake decreased (P < 0.05) by >50% in comparison with control after mucosal addition of the SGLT-1 inhibitor, phlorizin (100 micromol/L). Serosal preincubation with 100 micromol/L epinephrine increased (P < 0.05) the phlorizin-sensitive glucose uptake in the absence and presence of indomethacin (10 micromol/L). The effect of epinephrine was simulated by beta- (100 micromol/L isoproterenol) and beta(2)-receptor agonists (10 micromol/L terbutaline), as well as by direct stimulation of adenylyl cyclase (10 micromol/L forskolin). The serosal addition of methoxamine, clonidine, dobutamine or BRL 37344 had no effect. Inhibition of protein kinase A with 2 micromol/L H 89 completely abolished the stimulation of glucose uptake by epinephrine. We conclude that ruminal SGLT-1 can be stimulated via beta(2)-dependent generation of cyclic adenosine monophosphate.


Levodopa-induced dyskinesia: interplay between the N-methyl-D-aspartic acid receptor and neuroinflammation.
Parkinson's disease (PD) is a common neurodegenerative disorder of middle-aged and elderly people, clinically characterized by resting tremor, myotonia, reduced movement, and impaired postural balance. Clinically, patients with PD are often administered levodopa (L-DOPA) to improve their symptoms. However, after years of L-DOPA treatment, most patients experience complications of varying severity, including the "on-off phenomenon", decreased efficacy, and levodopa-induced dyskinesia (LID). The development of LID can seriously affect the quality of life of patients, but its pathogenesis is unclear and effective treatments are lacking. Glutamic acid (Glu)-mediated changes in synaptic plasticity play a major role in LID. The N-methyl-D-aspartic acid receptor (NMDAR), an ionotropic glutamate receptor, is closely associated with synaptic plasticity, and neuroinflammation can modulate NMDAR activation or expression; in addition, neuroinflammation may be involved in the development of LID. However, it is not clear whether NMDA receptors are co-regulated with neuroinflammation during LID formation. Here we review how neuroinflammation mediates the development of LID through the regulation of NMDA receptors, and assess whether common anti-inflammatory drugs and NMDA receptor antagonists may be able to mitigate the development of LID through the regulation of central neuroinflammation, thereby providing a new theoretical basis for finding new therapeutic targets for LID.


What is the moral basis of the authority of family members to act as surrogates for incompetent patients?
... The authority of family members should be understood as presumptive; that is, there is a moral presumption that a close family member should serve as surrogate for an incompetent patient. That presumption can be overcome or rebutted in a particular case, either when there is sufficient evidence that the usual reasons supporting this presumption do not hold or when the surrogate's decision exceeds appropriate limits of surrogates' decision-making discretion. In order to clarify these hard cases and appropriate public policy, we need a much deeper and more complex analysis than either the conventional view, or the alternative account that Pearlman and colleagues provide. I have sought here only to point toward some of the other grounds that a full account of family members' authority as surrogates would have to develop and explore in much more detail....