Intestinal bacteria and development of the antibody repertoire.
Extract: The function of the immune system is to protect the host from invasion by pathogenic microorganisms. Accordingly, most studies of host-microbial interactions have focused on pathogenic agents. The most common and intricate host-microbial interactions are, however, those between the host and non-pathogenic microorganisms that have taken up residence within the host, especially within the gastrointestinal tract. The lower gastrointestinal tract of mammals provides one of the best examples in nature of mutually beneficial association between host and colonizing foreign microorganisms. Between 500 and 1,000 microbial species colonize the mammalian colon to a density of approximately 1,000,000,000,000 bacteria per gram of content, comprising in total 100 times more cells than those that make up the host itself. Over the period of evolution, mammals have not only developed immunological tolerance mechanisms to accommodate this resident community, but they also have come to rely on these intestinal commensals for their own normal development. Studies of germfree and gnotobiotic animals revealed that the intestinal microbiota influences many aspects of immunity including development and function of mucosal immunity, development of oral tolerance and generation of the antibody repertoire. A recent study demonstrated that capsular polysaccharide produced by the commensal bacteria, Bacteroides fragilis, stimulates maturation of the developing immune system by contributing to the generation of CD4+ T cells and the proper T helper 1/T helper 2 cytokine balance.


Too stringent patient selection criteria in a clinical trial of alpha-blockers reduce the value of the results.
The patient selection criteria in a clinical trial of an alpha-blocker for the treatment of benign prostatic hypertrophy were such that 85% of the patients on the waiting lists of 4 hospitals had to be excluded. The value of such a trial is discussed. Trial protocols should be designed to allow the enrollment of patients truly representative of the patients for which the treatment is intended.


Interaction of regular exercise and chronic nitroglycerin treatment on blood pressure and rat aortic antioxidants.
Many cardiac patients undergo exercise conditioning with or without medication. Therefore, we investigated the interaction of exercise training and chronic nitroglycerin treatment on blood pressure (BP), aortic nitric oxide (NO), oxidants and antioxidants in rats. Fisher 344 rats were divided into four groups and treated as follows: (1) sedentary control, (2) exercise training (ET) for 8 weeks, (3) nitroglycerin (15 mg/kg, s.c. for 8 weeks) and (4) ET+nitroglycerin. BP was monitored with tail-cuff method. The animals were sacrificed 24 h after the last treatments and thoracic aorta was isolated and analyzed. Exercise training on treadmill for 8 weeks significantly increased respiratory exchange ratio (RER), aortic NO levels, and endothelial nitric oxide synthase (eNOS) protein expression. Training significantly enhanced aortic glutathione (GSH), reduced to oxidized glutathione (GSH/GSSG) ratio, copper/zinc-superoxide dismutase (CuZn-SOD), Mn-SOD, catalase (CAT), glutathione peroxidase (GSH-Px) glutathione disulfide reductase (GR) activities and protein expressions. Training significantly depleted aortic malondialdehyde (MDA) and protein carbonyls without change in BP. Nitroglycerin administration for 8 weeks significantly increased aortic NO levels and eNOS protein expression. Nitroglycerin significantly enhanced aortic Mn-SOD, CAT, GR and glutathione-S-transferase (GST) activities and protein expressions with decreased MDA levels, protein carbonyls and BP. Interaction of training and nitroglycerin treatment significantly increased aortic NO levels, eNOS protein expression, GSH/GSSG ratio, antioxidant enzymes and normalized BP. The data suggest that the interaction of training and nitroglycerin maintained BP by up-regulating the aortic NO and antioxidants and reducing the oxidative stress in rats.


Outcomes of a hepatitis C screening protocol in at-risk adults with prior cardiac surgery.
Symptoms associated with hepatitis C infection often do not develop until an advanced stage of liver disease. Prior to 1992, reliable testing for hepatitis C was unavailable, resulting in potential patient exposure during cardiopulmonary bypass. As the hepatitis C prevalence in our center was unknown, a screening protocol for patients who underwent surgery prior to 1992 was developed. Patients evaluated in the Wisconsin Adult Congenital Heart Disease program who underwent surgery prior to 1992 were screened for hepatitis C as part of their initial clinical evaluation. The hepatitis C-positive patients were assessed for risk factors, level of hepatic involvement, whether they received treatment, and whether viral clearance was obtained. A total of 147 patients (53% male) underwent testing. Seven (4.8%) patients had evidence of chronic hepatitis C infection, which is higher than the Wisconsin reported prevalence of 0.3%. Six of the seven patients had elevated liver enzymes at time of diagnosis. No relationship was found between hepatitis C infection and number of surgeries, year of surgery, or age at surgery. Four patients had hepatitis C genotype 1, but none achieved viral clearance despite three having received treatment. Three had genotype 2, were treated, and had viral clearance. No hepatitis C-positive patient developed cirrhosis or required liver transplant. Hepatitis C infection in patients with congenital heart disease who underwent surgical palliation prior to 1992 is common, with prevalence higher than the general population. Our data emphasize the continued importance of screening the high-risk adult congenital heart disease patients.


WT1 IgG antibody for early detection of nonsmall cell lung cancer and as its prognostic factor.
There are urgent needs to develop methods for early detection of nonsmall cell lung cancer (NSCLC) because of its increasing incidence and poor prognosis. Here, we analyzed the production of IgG antibody (WT1 Ab) against WT1 (Wilms' tumor gene) protein that was overexpressed in the majority of NSCLC. Enzyme-linked immuno-sorbent assay showed that WT1 Ab was produced in all of 91 NSCLC patients and 70 healthy individuals and that WT1 Ab titers were significantly higher in NSCLC patients compared with healthy individuals. When the cut-off level of WT1 Ab titers were fixed at mean + 3SD of those in healthy individuals, 26.4% of NSCLC patients had WT1 Ab titers over the cut-off level, and positive rates of WT1 Ab at each clinical stage were 25.0, 30.8 and 38.4% in stage I, II and III NSCLC, respectively. When WT1 Ab was combined with CEA or CYFRA for detection of NSCLC, positive detection rates increased from 25.0 to 34.1 and 31.8%, respectively, in stage I and from 38.4 to 69.2 and 46.1%, respectively, in stage III, but not changed in stage II. Western blot analysis showed that dominant subclass of WT1 Ab was Th1-type IgG2. Interestingly, elevation of WT1 Ab titers was significantly associated with longer disease-free survival in patients with stages I-III NSCLC. These results showed that WT1 Ab could be a useful marker for early detection of NSCLC and its prognostic prediction. These results also suggested that WT1-specific immune responses played an important role in anti-cancer immunity in NSCLC.


[Characteristics of biocrusts in croplands and their effects on surface soil disintegration in the black soil region of Northeast China].
We selected typical croplands in the black soil region of Northeast China to analyze the characteristics of biocrusts during the growing season, including species composition, thickness, coverage, and biomass (chlorophyll content). We collected bareground soil and biocrusts samples with chlorophyll content of 5-15, 15-25, 25-35, and 35-50 mg·g-1, and measured the soil disintegration rate and soil maximum disintegration ratio of each sample using a force gauge in the laboratory. The results showed that: 1) biocrusts dominated by algae and moss were frequently developed in the croplands, with Stigeoclonium and Bryum capillare as the most common species, respectively. The thickness and biomass of algal crusts were significantly lower than moss crusts, with a successional trend from algal crusts to moss crusts. 2) The coverage, thickness, and biomass of biocrusts in croplands were negatively correlated with the frequency and intensity of tillage disturbance. For instance, the values of those characterisitics were only 27.8%, 1.52 mm, and 6.49 mg·g-1 on average, respectively, in traditional tillage croplands, and increased to 83.5%, 2.74 mm, and 34.16 mg·g-1, respectively, in the croplands with conservational tillage. 3) Biocrusts considerably reduced the disintegration of surface soil, particularly in the layer of biocrusts. Compared to the bareground soil, the soil disintegration rate of biocrusts, with four levels of biomass (with chlorophyll content of 5-15, 15-25, 25-35, and 35-50 mg·g-1), was reduced by 43.1%, 50.1%, 55.5%, and 59.8%, respectively, while the soil maximum disintegration ratios were reduced by 11.4%, 17.7%, 33.2%, and 36.6%, respectively. 4) Soil disintegration rate and maximum disintegration ratio were significantly and negatively correlated with the biomass and thickness of biocrusts, indicating that the impacts of biocrusts on soil disintegration were primarily caused by the improvements in physical properties of surface soil. In conclusion, biocrusts were frequently deve-loped in croplands in the black soil region of Northeast China, owing to less disturbance following the conversion from traditional tillage to conservational tillage. They had the potential to protect surface soil against disintegration and improve soil anti-scourability, which was critical for soil conservation in croplands in this region.


Twelve-month persistency with oral 5-aminosalicylic acid therapy for ulcerative colitis: results from a large pharmacy prescriptions database.
Patients receiving 5-aminosalicylic acid (5-ASA) require long-term therapy to achieve good outcomes. Persistency (duration of time from initiation to discontinuation of therapy) is therefore an important consideration. To evaluate persistency in patients receiving various oral 5-ASA formulations. This retrospective, 12-month, cohort study examined new-starter patients (any age and diagnosis) from a large United States pharmacy database who filled a prescription for oral 5-ASA [Lialda(®), Asacol(®), Pentasa(®) 250 or 500 mg, balsalazide (generic and Colazal(®)), and olsalazine (Dipentum(®))] between March and September 2007. Persistency was evaluated monthly on the basis of prescription refill rates. Prescription and refill records were identified for 44,191 patients receiving oral 5-ASA. After 1 year, 20% of patients receiving Lialda were considered persistent and classified as continuing (refilling within a timeframe of up to twice the duration of the prescription), compared with 9% receiving Asacol, 7 (250 mg) and 10% (500 mg) receiving Pentasa, 10% receiving balsalazide, and 10% receiving Dipentum. Overall persistency with oral 5-ASA therapy was low. However, patients receiving once-daily Lialda had significantly higher persistency after 1 year of treatment than patients receiving other oral 5-ASA therapies.


Effects of pronase on isolated chloroplasts.
Subjecting isolated spinach chloroplasts to mild proteolysis (10-minute incubation at 20 C in 500 micrograms per milliliter pronase) caused chloroplast clumping but did not affect their integrity as measured by their ability to carry out light stimulated, glycerate-3-P-dependent O(2) evolution. Transmission electron microscopy revealed no detectable differences between the control and treated plastids. Mild proteolysis inactivated exogenously added pyruvate kinase and should be a useful technique in certain enzyme distribution studies.


Detection of galectin-3 and localization of advanced glycation end products (AGE) in human chronic skin wounds.
The matricellular protein galectin-3 (Gal-3) is upregulated in excisional skin repair in rats where it has been shown to modulate the inflammatory phase of repair. Recent research into kidney pathology has implicated Gal-3 as a receptor for advanced glycation end products (AGE), resulting in the binding and clearance of these molecules. AGEs are thought to contribute to defective skin repair in diabetic patients as well as a result of the normal aging process. However, the distribution and localization of Gal-3 and AGEs has never been performed in human chronic skin wound tissue. Using immunohistochemistry, the localization of Gal-3 and AGEs in tissue isolated from chronic wounds and non-involved skin from the same patient was investigated. Of the 16 patients from which tissue was isolated, 13 had type II diabetes, one had type I diabetes and 2 patients without diabetes were also examined. In non-involved dermis, Gal-3 was detected strongly in the epidermis and in the vasculature. However, at the wound edge and in the wound bed, the level of Gal-3 labelling was greatly reduced in both the epidermis and vasculature. Labelling of serial sections for Gal-3 and AGE demonstrated that where Gal-3 immunoreactivity is reduced in the epidermis and vasculature, there is a concomitant increase in the level of AGE staining. Interestingly, similar labelling patterns were evident in diabetic and non-diabetic patients. The results from our study demonstrate an inverse correlation between Gal-3 and AGEs localization, suggesting that Gal-3 may protect against accumulation of AGEs in wound healing.


Diplotype trend regression analysis of the ADH gene cluster and the ALDH2 gene: multiple significant associations with alcohol dependence.
The set of alcohol-metabolizing enzymes has considerable genetic and functional complexity. The relationships between some alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) genes and alcohol dependence (AD) have long been studied in many populations, but not comprehensively. In the present study, we genotyped 16 markers within the ADH gene cluster (including the ADH1A, ADH1B, ADH1C, ADH5, ADH6, and ADH7 genes), 4 markers within the ALDH2 gene, and 38 unlinked ancestry-informative markers in a case-control sample of 801 individuals. Associations between markers and disease were analyzed by a Hardy-Weinberg equilibrium (HWE) test, a conventional case-control comparison, a structured association analysis, and a novel diplotype trend regression (DTR) analysis. Finally, the disease alleles were fine mapped by a Hardy-Weinberg disequilibrium (HWD) measure (J). All markers were found to be in HWE in controls, but some markers showed HWD in cases. Genotypes of many markers were associated with AD. DTR analysis showed that ADH5 genotypes and diplotypes of ADH1A, ADH1B, ADH7, and ALDH2 were associated with AD in European Americans and/or African Americans. The risk-influencing alleles were fine mapped from among the markers studied and were found to coincide with some well-known functional variants. We demonstrated that DTR was more powerful than many other conventional association methods. We also found that several ADH genes and the ALDH2 gene were susceptibility loci for AD, and the associations were best explained by several independent risk genes.


Magneto-structural correlations in dinuclear Mn(III) compounds with formula [{Mn(L)(NN)}(μ-O)(μ-2-RC6H4COO)2{Mn(L')(NN)}]n+.
Three dinuclear Mn(III) compounds with oxo and carboxylato bridges have been synthesized and characterized by X-ray diffraction: [{Mn(L)(NN)}(μ-2-ClC(6)H(4)COO)(2)(μ-O){Mn(L')(NN)}](n+) with NN = 2,2'-bipyridine (1 and 2) or 1,10-phenanthroline (3). The counteranion is either NO(3)(-) (1 and 3) or ClO(4)(-) (2) and the monodentate positions (L, L') could be occupied by molecules of water or the counteranion. For compound 1, L = H(2)O and L' = NO(3)(-); compound 2 shows two different dinuclear units and L and L' could be H(2)O or ClO(4)(-), and for compound 3 both monodentate positions are occupied by nitrate anions. The magnetic properties of the three compounds have been analyzed using the Hamiltonian H = -JS(1)·S(2). Compound 1 exhibits a dominant ferromagnetic behavior, with J = 3.0 cm(-1), |D(Mn)| = 1.79 cm(-1), |E(Mn)| = 0.60 cm(-1) with intermolecular interactions zJ' = -0.18 cm(-1). Due to the anisotropy of the Mn(III) ions, the ground state S = 4 shows ZFS with |D(4)| = 0.58 cm(-1). Compounds 2 and 3 show antiferromagnetic couplings, with J = -10.9 and -0.3 cm(-1), respectively. The magnetic interaction in this kind of compound depends on several structural factors. In the present work, the distortion around manganese ions, the torsion angle between the phenyl ring and the carboxylate group and the relative disposition of the coordination octahedra have been analyzed.


Blue-light dependent ROS formation by Arabidopsis cryptochrome-2 may contribute toward its signaling role.
Cryptochromes are blue-light absorbing flavoproteins with many important signaling roles in plants, including in de-etiolation, development, and stress response. They interact with downstream signaling partners such as transcription factors and components of the proteasome, and thereby alter regulation of nuclear gene expression in a light dependent manner. In a prior study, it has also been shown that Arabidopsis cry1 activation by blue light results in direct enzymatic conversion of molecular oxygen (O2) to ROS (reactive oxygen species) in vivo leading to cell death in overexpressing lines. Here we extend these observations to show that Atcry2 is translocated from the cytosol to the nucleus in response to blue light illumination, resulting in nuclear accumulation of ROS in expressing insect cell cultures. These observations suggest that ROS formation may represent a novel means of signaling by Atcry2 distinct from, and perhaps complementary to, the currently known mechanism of light-mediated conformational change.


Comparison of the phenolic component profiles of skullcap (Scutellaria lateriflora) and germander (Teucrium canadense and T. chamaedrys), a potentially hepatotoxic adulterant.
Scutellaria lateriflora, commonly known as skullcap, is used as an ingredient in numerous herbal products. Unfortunately, it has occasionally been adulterated with Teucrium canadense or T. chamaedrys, commonly known as germander, which contains potentially hepatotoxic diterpenes. Chromatographic profiles of the phenolic components provide a means of distinguishing between these plants and enhancing public safety. To develop a chromatographic method for the identification of Scutellaria lateriflora and two Teucrium species and to quantify the latter as adulterants. Samples were extracted with aqueous methanol and the extracts were analysed using a standardised LC-DAD-ESI/MS profiling method to obtain their phenolic profiles. Skullcap contained primarily flavonoids, while the major phenolic components of the two Teucrium species were the phenylethanoids, verbascoside and teucrioside. Using the phenylethanoids as markers, it was possible to clearly distinguish between the two genus and to determine 5% Teucrium mixed with Scutellaria using either ultraviolet absorption spectrometry or mass spectrometry in the total ion count mode. Using MS in the selective ion monitoring (SIM) mode, 1% Teucrium could be measured. This study showed that chromatographic profiling was able to identify Scutellaria and Teucrium, separately and when mixed together.


NLRP3 Inflammasome Activation Inhibitors in Inflammation-Associated Cancer Immunotherapy: An Update on the Recent Patents.
Inflammasomes are recognized as key regulators in innate immunity from the pathogenic to endogenous danger signals. Although controlled activation of inflammasome is highly beneficial, dysregulation of inflammasome activation plays central role in various autoimmune, inflammatory disorders and aid in promoting various forms of cancers in humans such as breast cancer, fibrosarcoma, gastric carcinoma, and lung metastasis. NLRP3 inflammasome activation has been emerged as a topic of interest and is under profound investigation for its involvement in multiple forms of cancers. This review emphasizes an overview of the recent patents on NLRP3 inflammasome activation inhibitors with their relevant biological/pharmacological properties for the prevention and treatment of inflammation-associated cancer disorders. Data were obtained from online patent searchers such as World Intellectual Property Organization (WIPO®), Free Patent Online (FPO), Espacenet® and Google Patents. Several NLRP3 inflammasome activation inhibitors were recently patented from naturally derived and synthetic agents mainly by academic researchers. Most of the claimed patents have been validated and confined to cell lines and animal models limiting their entry into clinical settings. The vigorous effort to discover and develop agents to specifically inhibit NLRP3 inflammasome activation, may pave the way to therapeutic intervention targeting inflammasome-regulated pathways that are involved in the pathogenesis of various forms of cancer.


mTOR plays a pivotal role in multiple processes of enamel organ development principally through the mTORC1 pathway and in part via regulating cytoskeleton dynamics.
We herein report that deletion of mTOR in dental epithelia caused defective development of multiple cell layers of the enamel organ, which culminated in tooth malformation and cystogenesis. Specifically, cells of the stellate reticulum and stratum intermedium were poorly formed, resulting in cystic changes. The pre-ameloblasts failed to elongate along the apical-basal axis and persisted vigorous expression of Sox2 and P63, which are normally downregulated during cytodifferentiation. Expression of amelogenic markers was also attenuated in mutants. Cell proliferation and cell sizes in mutants were significantly reduced over time. Importantly, we found reduced amounts and aberrant aggregations of cytoskeletal components in mutants, along with attenuated expression of cytoskeleton regulator Cdc42, whose epithelial deletion causes a similar phenotype. Moreover, disruption of actin assembly in an organ culture system affected cell proliferation and cytodifferentiation of tooth germs, supporting a causative role of mTOR-regulated cytoskeleton dynamics for the observed phenotype of mTOR mutant mice. In further support of this view, we showed that mTOR overactivation caused increased cytoskeletal component synthesis and assembly, along with accelerated cytodifferentiation in the enamel organ. Finally, we demonstrated that mTOR regulated enamel organ development principally through the mTORC1 pathway.


Correlates of smoking discarded cigarettes in a sample of low-income adults.
Unconventional smoking behaviors such as smoking used or discarded cigarettes may increase the risk of nicotine dependence and exposure to toxins. To better understand low-income smokers who smoke discarded cigarettes and to inform effective tobacco cessation strategies, the current study examined potential correlates not considered in prior studies. This secondary analysis examined baseline data from 1936 low-income smokers participating in a randomized cessation trial. To assess smoking discarded cigarettes, participants were asked: "In the past 30 days, have you smoked what's left of a cigarette that someone else left behind?" Unadjusted and adjusted logistic regression were used to explore associations between smoking discarded cigarettes and social needs, social environment, mental and physical health, other smoking-related behaviors, and demographic characteristics. One in six participants reported smoking discarded cigarettes. Younger smokers, men, smokers with lower incomes and those who were not employed were more likely to smoke discarded cigarettes. Other correlates included having unmet social needs (transportation, food, housing, physical safety, and neighborhood safety), living with other smokers, worse mental health, greater perceived stress, heavier smoking, using other tobacco products, and bumming cigarettes from others. In a multivariable model, income, social environment, and other smoking behaviors emerged as significant correlates. In addition to financial hardship, mental health, and nicotine dependence, the social needs, social environment, and other smoking behaviors of low-income smokers are important correlates of smoking discarded cigarettes. Future research to understand and address tobacco health disparities should examine these relationships longitudinally.


Ultrasonic Assessment of Cervical Heterogeneity for Prediction of Spontaneous Preterm Birth: A Feasibility Study.
In a normal pregnancy, cervical collagen fibers remain organized in predictable patterns throughout most of the gestation. Cervical remodeling reflects a rearrangement of collagen fibers in which they become increasingly disordered and contribute to the pathogenesis of spontaneous preterm birth. Quantitative ultrasound analysis of cervical tissue echotexture may have the capacity to identify microstructural changes before the onset of cervical shortening. The primary objective of this study was to examine the utility of a novel quantitative sonographic marker, the cervical heterogeneity index (HI), which reflects the relative organization of cervical collagen fibers. Also, we aimed to determine an optimal HI cut-point to predict spontaneous preterm birth. This retrospective cohort study employed a novel image-processing technique on transvaginal ultrasound images of the cervix in gestations between 14 and 28 completed weeks. The transvaginal sonography images were analyzed in MATLAB (MathWorks, Natick, MA) using a custom image-processing technique that assessed the relative heterogeneity of the cervical tissue. A total of 151 subjects were included in the study. The mean HI in subjects who delivered preterm and at term was 8.28 ± 3.73 and 12.35 ± 5.80, respectively (p < 0.0001). Thus, decreased tissue heterogeneity was associated with preterm birth, and increased tissue heterogeneity was associated with delivery at term. In our study population, preterm birth was associated with a short cervix (<2.5 cm), history of preterm birth and lower HI, and our findings indicate that HI may improve prediction of preterm birth. Quantitative ultrasound measurement of the cervical HI is a promising, noninvasive tool for early prediction of spontaneous preterm birth.


Steric Effects in the Deposition Mode and Drug-Delivering Efficiency of Nanocapsule-Based Multilayer Films.
Using surface-initiated atom transfer radical polymerization (ATRP), block polymers with a series of quaternization degrees were coated on the surface of silica nanocapsules (SNCs) by the "grafting-from" technique. Molnupiravir, an antiviral medicine urgently approved for the treatment of SARS-CoV-2, was encapsulated in polymer-coated SNCs and further incorporated into well-defined films with polystyrene sulfonate (PSS) homopolymers by layer-by-layer (LBL) self-assembly via electrostatic interactions. We investigated the impact of the quaternization degree of the polymers and steric hindrance of functional groups on the growth mode, swelling/deswelling transition, and drug-delivering efficiency of the obtained LBL films. The SNCs were derived from coronas of parent block polymers of matched molecular weights-poly(N-isopropylacrylamide)-block-poly(N,N-dimethylaminoethyl methacrylate) (PNIPAM-b-PDMAEMA)-by quaternization with methyl sulfate. As revealed by the data results, SNCs with coronas with higher quaternization degrees resulted in a larger layering distance of the film structure because of weaker ionic pairing (due to the presence of a bulky methyl spacer) between SNCs and PSS. Interestingly, when comparing the drug release profile of the encapsulated drugs from SNC-based films, the release rate was slower in the case of capsule coronas with higher quaternization degrees because of the larger diffusion distance of the encapsulated drugs and stronger hydrophobic-hydrophobic interactions between SNCs and drug molecules.


Adrenal incidentalomas in the laparoscopic era and the role of correct surgical indications: observations from 255 consecutive adrenalectomies in an Italian series.
The purpose of our study was to evaluate the impact of laparoscopic adrenalectomy on patients with incidentalomas. We analyzed the results of a multi-centre trial that was performed to evaluate the effectiveness of imaging (computed tomography and magnetic resonance imaging) to obtain a correct preoperative diagnosis. We obtained our data from the results of a questionnaire that was distributed by mail or email in May 2005 to several surgical units operating in the Campania Region, Italy. Lap Club, a collaborative laparoscopic surgery study group founded in Naples in 1995, distributed the questionnaire. Thirteen centres participated in the audit. In all, we analyzed 255 adrenalectomies performed on 250 patients. We performed statistical analysis using SPSS software. The distribution of pathologic findings demonstrates that the number of lesions caused by cancer discovered from a preoperative indication of incidentaloma has been even smaller (1/114, 0.8%) than the previous numbers reported in the literature. Moreover, whereas most patients with adrenal cancer had lesions larger than 6 cm (7/8, 87.5%), the majority of patients with adrenal metastases had lesions 6 cm or smaller (10/12, 83.3%). Different indications for adrenalectomy emerged on comparison of endocrine surgery units with general surgery units. This difference appears to be significant (p < 0.001), especially on evaluation of the number of nonfunctioning adenomas and the number of endocrine lesions that were observed and treated. Laparoscopy remains the gold standard method for adrenalectomy, but its availability must not obligate physicians to treat with surgery when an incidentaloma is detected through imaging. Adrenal malignancies when metastatic are often 6 cm or smaller. If they are single and they originated from a non-small lung cancer, they must be removed. The endocrine surgery unit remains the best setting to evaluate and treat adrenal gland surgical pathology.


Antioxidant Therapies for Ulcerative Dermatitis: A Potential Model for Skin Picking Disorder.
Skin Picking Disorder affects 4% of the general population, with serious quality of life impacts, and potentially life threatening complications. Standard psychoactive medications do not help most patients. Similarly, Mouse Ulcerative Dermatitis (skin lesions caused by excessive abnormal grooming behavior) is very common in widely used inbred strains of mice, and represents a serious animal welfare issue and cause of mortality. Treatment options for Ulcerative Dermatitis are largely palliative and ineffective. We have proposed mouse Ulcerative Dermatitis as a model for human Skin Picking Disorder based on similar epidemiology, behavior, and its comorbidity and mechanistic overlap with hair pulling (trichotillomania). We predicted that mouse Ulcerative Dermatitis would be treated by N-Acetylcysteine, as this compound is highly effective in treating both Skin Picking Disorder and Trichotillomania. Furthermore, we hypothesized that N-Acetylcysteine's mode of action is as a precursor to the production of the endogenous antioxidant glutathione in the brain, and therefore intranasal glutathione would also treat Ulcerative Dermatitis. Accordingly, we show in a heterogenous prospective trial, the significant reduction in Ulcerative Dermatitis lesion severity in mice receiving either N-acetylcysteine (oral administration) or glutathione (intranasal). The majority of mice treated with N-acetylcysteine improved slowly throughout the course of the study. Roughly half of the mice treated with glutathione showed complete resolution of lesion within 2-4 weeks, while the remainder did not respond. These findings are the first to show that the use of N-acetylcysteine and Glutathione can be curative for mouse Ulcerative Dermatitis. These findings lend additional support for mouse Ulcerative Dermatitis as a model of Skin Picking Disorder and also support oxidative stress and glutathione synthesis as the mechanism of action for these compounds. As N-Acetylcysteine is poorly tolerated by many patients, intranasal glutathione warrants further study as potential therapy in Skin Picking, trichotillomania and other body-focused repetitive behavior disorders.


Trend Change in the Intellectual Disability Nursing Home Census From 1977 to 2004.
The Omnibus Budget Reconciliation Act (OBRA) of 1987 was expected to reduce inappropriate residential placements of persons with intellectual disability (ID) in nursing homes. Utilizing the nationally representative 1977, 1985, 1995, and 2004 National Nursing Home Surveys (NNHS), we estimate trend change in the ID nursing home census pre- and post-OBRA. We find a marked decrease in number and percentage, and a shift in the age distribution of the ID nursing home census, most pronounced between 1985 and 1995. We contend that these trend changes, concurrent with growth in the overall nursing home population, provide empirical evidence that policy changes that occurred during the OBRA enactment period were successful in reducing inappropriate residential placements of persons with ID in nursing homes.


Thromboembolism following multiple trauma.
The true incidence of thromboembolic complications following multiple trauma is unknown, and no method of prophylaxis has been shown to be both safe and effective in managing seriously injured patients. In this prospective study, 113 trauma patients were assigned on admission to receive either low-dose heparin (LDH), (5,000 U subcutaneously every 12 hours) or to wear sequential compression devices (SCDs) as prophylaxis against the development of deep venous thrombosis (DVT). Both groups of patients were serially studied with duplex venous ultrasound imaging to detect thrombus in the veins of the thigh. Ventilation-perfusion lung scans and pulmonary angiograms were performed when pulmonary embolism (PE) was suspected clinically. There were 12 patients who had thromboembolic complications, including 9 of 76 in the SCD group (12%) and 3 of 37 in the LDH group (8%). Five patients had DVT only, four had PE without detectable DVT, and three had both DVT and PE. None of the patients with PE died, and there were no major complications associated with either method of prophylaxis. Compared with the patients who did not develop DVT/PE, those with thromboembolic complications were older (49 +/- 23 vs. 36 +/- 17 years, p less than 0.02), spent more hospital days immobilized (24 +/- 15 vs. 10 +/- 13 days, p less than 0.001), received more transfusions (11 +/- 12 vs. 3 +/- 5 U, p less than 0.001) and had clotting abnormalities on admission, as demonstrated by prolonged PTT values (39 +/- 28 vs. 26 +/- 5 seconds, p less than 0.001). It appears that there is an identifiable subgroup of injured patients at highest risk for PE who warrant both prophylaxis and close surveillance for DVT.


Activated protein C resistance and anticoagulant proteins in young adults with central retinal vein occlusion.
Central retinal vein occlusion is a disease that is most common in old people, and often associated with atherosclerosis, hypertension, diabetes or glaucoma. Since these diseases are much less evident in young people, we wanted to investigate the prevalence of disorders in the most common anticoagulant proteins in a group of young patients with central retinal vein occlusion. 37 consecutive patients younger than 50 years and with a history of central retinal vein occlusion, were analysed for deficiencies of natural inhibitors of coagulation (protein C, S, and antithrombin III), plasminogen, resistance to activated protein C, and the presence of anticardiolipin or lupus anticoagulants. Anticoagulant protein deficiencies were found in 4 patients (11%) and activated protein C resistance in 7 patients (19%). Anticardiolipin or lupus anticoagulants were not found in the patients. Activated protein C resistance and anticoagulant protein deficiencies seem to be important factors to the etiology to central retinal vein occlusion in young patients.


Initiation of therapy during primary HIV type 1 infection results in a continuous decay of proviral DNA and a highly restricted viral evolution.
A latent pool of HIV-1 is established early in memory CD4+ T lymphocytes and persists during antiretroviral therapy. Also, viral replication may continue in subjects despite undetectable viremia. However, it remains unclear whether this residual replication results in any significant sequence evolution. We were therefore interested in studying the viral evolution and HIV-1 DNA dynamics in subjects with primary infection receiving or not receiving early potent antiretroviral therapy. In 16 subjects, HIV-1 DNA load was monitored from 1 to 23 days, up to 1253 days, after onset of symptoms. Extensive sequential cloning and sequence analysis of the V3 region was performed in four subjects. In the treated subjects a continuous decline in the proviral load was found, corresponding to a half-life of about 6 months. As expected in newly infected individuals the founder virus populations showed high intrasubject sequence similarity. Also, a limited increase in the viral divergence was detected during the first 6 months in three treated subjects. Thereafter, no significant sequence changes were found despite analysis of a large number of clones. Our data thus suggest that early and successful therapy in compliant subjects with primary HIV-1 infection results in a highly restricted viral evolution and a decline in the proviral load close to the decay rate of human memory T lymphocytes.


Epigenetic Modification of the von Willebrand Factor Promoter Drives Platelet Aggregation on the Pulmonary Endothelium in Chronic Thromboembolic Pulmonary Hypertension.
Rationale: von Willebrand factor (vWF) mediates platelet adhesion during thrombosis. While chronic thromboembolic pulmonary hypertension (CTEPH) is associated with increased plasma levels of vWF, the role of this protein in CTEPH has remained enigmatic. Objectives: To identify the role of vWF in CTEPH. Methods: CTEPH-specific patient plasma and pulmonary endarterectomy material from patients with CTEPH were used to study the relationship between inflammation, vWF expression, and pulmonary thrombosis. Cell culture findings were validated in human tissue, and proteomics and chromatin immunoprecipitation were used to investigate the underlying mechanism of CTEPH. Measurements and Main Results: vWF is increased in plasma and the pulmonary endothelium of CTEPH patients. In vitro, the increase in vWF gene expression and the higher release of vWF protein upon endothelial activation resulted in elevated platelet adhesion to CTEPH endothelium. Proteomic analysis revealed that nuclear factor (NF)-κB2 was significantly increased in CTEPH. We demonstrate reduced histone tri-methylation and increased histone acetylation of the vWF promoter in CTEPH endothelium, facilitating binding of NF-κB2 to the vWF promoter and driving vWF transcription. Genetic interference of NFκB2 normalized the high vWF RNA expression levels and reversed the prothrombotic phenotype observed in CTEPH-pulmonary artery endothelial cells. Conclusions: Epigenetic regulation of the vWF promoter contributes to the creation of a local environment that favors in situ thrombosis in the pulmonary arteries. It reveals a direct molecular link between inflammatory pathways and platelet adhesion in the pulmonary vascular wall, emphasizing a possible role of in situ thrombosis in the development or progression of CTEPH.


Effect of sweeteners on the survival and behaviour of Bactrocera dorsalis (Hendel) (Diptera: Tephritidae).
The oriental fruit fly Bactrocera dorsalis (Hendel) (Diptera: Tephritidae) causes serious damage that affects fruit production. Chemical insecticides have been widely used for the prevention and control of this destructive pest. However, the resistance of B. dorsalis to these compounds has become a serious problem. This study tested six sweeteners for their toxicity to B. dorsalis. B. dorsalis fed on erythritol, aspartame and saccharin exhibited significantly higher mortality than those fed on sucrose. Flies fed on erythritol died faster than did the control flies (water). However, no dose-dependent effects were observed at the concentrations tested. These three sweeteners decreased the climbing ability of B. dorsalis. Notably, adults fed on saccharin exhibited significantly decreased climbing ability after 12 h compared with those fed on sucrose. Additionally, these three sweeteners had a negative effect on the frequency and duration of the flies' behaviour patterns (flying, walking, grooming and inactivity). Saccharin not only induced a marked reduction in the frequency of flights and walks but also induced decreases in the time spent flying and walking and increases in inactivity compared with sucrose. Erythritol induced a reduction in movement and increased the time spent inactive compared with the control and other treatments. Three sweeteners had significant negative effects on the survival of B. dorsalis. Erythritol was toxic to B. dorsalis. Aspartame and saccharin also decreased the survival and behaviour of adult flies and may be toxic to (or contribute to poor nutrition in) B. dorsalis. These sweeteners could therefore be developed as additive ingredients in baits.


What Is It That I'm Trying to Achieve? Classroom Goals from a Content Perspective.
In this article, goals are discussed with respect to content, that is, as cognitive representations of what it is that an individual is trying to achieve in a given situation. In support of this perspective, I argue that a focus on the content of students' goals can provide unique and valuable insights into ways in which students' multiple social and academic goals might influence their academic accomplishments. Several models of relations between multiple goals are described. First, from a developmental perspective, relations among social and academic goals might be one-directional, with fundamental orientations toward the self and the social environment guiding efforts to be academically competent. Second, relations between goals also can be complementary, with social and task-related goal pursuit independently contributing to academic achievement. Finally, relations between social and academic goal pursuit can be reciprocal and hierarchical in nature, reflecting students' beliefs about how to achieve academic success. The significance of a goal content perspective in relation to other goal-related constructs also is discussed. Copyright 2000 Academic Press.


Dynamic contrast-enhanced MR imaging pharmacokinetic parameters as predictors of treatment response of brain metastases in patients with lung cancer.
To determine the diagnostic accuracy of pharmacokinetic parameters measured by dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) in predicting the response of brain metastases to antineoplastic therapy in patients with lung cancer. Forty-four consecutive patients with lung cancer, harbouring 123 newly diagnosed brain metastases prospectively underwent conventional 3-T MRI at baseline (within 1 month before treatment), during the early (7-10 weeks) and midterm (5-7 months) post-treatment period. An additional DCE MRI sequence was performed during baseline and early post-treatment MRI to evaluate baseline pharmacokinetic parameters (K trans, k ep, v e, v p) and their early variation (∆K trans, ∆k ep, ∆v e, ∆v p). The objective response was judged by the volume variation of each metastasis from baseline to midterm MRI. ROC curve analysis determined the best DCE MRI parameter to predict the objective response. Baseline DCE MRI parameters were not associated with the objective response. Early ∆K trans, ∆v e and ∆v p were significantly associated with the objective response (p = 0.02, p = 0.001 and p = 0.02, respectively). The best predictor of objective response was ∆v e with an area under the curve of 0.93 [95% CI = 0.87, 0.99]. DCE MRI and early ∆v e may be a useful tool to predict the objective response of brain metastases in patients with lung cancer. • DCE MRI could predict the response of brain metastases from lung cancer • ∆v e was the best predictor of response • DCE MRI could be used to individualize patients' follow-up.


Characterization of dextrins with different Dextrose Equivalents.
Dextrins are widely used for their functional properties and prepared by partial hydrolysis of starch using acid, enzymes, or combinations of both. The physiochemical properties of dextrins are dependent on their molecular distribution and oligosaccharide profiles. In this study, scanning electron microscopy (SEM), X-ray diffractometry (XRD), rapid viscoanalysis (RVA), high-performance Liquid Chromatography (HPLC) and gel permeation chromatography (GPC) were used to characterize dextrins prepared by common neutral and thermostable alpha-amylase hydrolysis. The dextrin granules displayed irregular surfaces and were badly damaged by the enzyme treatment. They displayed A-type X-ray diffraction patterns with a decrease of intensity of the characteristic diffraction peaks. The RVA profiles showed that the viscosity of dextrin decreased with the increase of its Dextrose Equivalent (DE) value. According to HPLC analysis, the molecular weight, degree of polymerization and the composition of oligosaccharides in dextrins were different.


Relative signal intensity on time-of-flight magnetic resonance angiography as a novel indicator of aggressive presentation of intracranial dural arteriovenous fistulas.
Asymptomatic dural arteriovenous fistulas (DAVFs) with cortical venous reflux (CVR) are now more commonly encountered. However, patients with an incidental onset may have a less aggressive clinical course. It is desirable to explore methods and indicators to predict the clinical outcomes. This study investigates whether the relative signal intensity (rSI) of the draining vessels on the time-of-flight magnetic resonance angiography is related to clinical behavior in patients with intracranial DAVFs. We retrospectively reviewed 36 intracranial DAVFs. The patients were categorized as those with either aggressive-presentation or non-aggressive-presentation (n = 16 and 20, respectively). The rSIs of the shunt points, affected sinuses, and veins with CVR were compared between the two groups. The two groups were not significantly different in terms of rSIs of the shunt points and affected sinuses (p = 0.37 and 0.41, respectively). However, a significant positive correlation was observed in the rSI of the veins with CVR between the aggressive and non-aggressive behavior groups (p < 0.0001). The rSI of the veins with CVR could serve as a reliable indicator of aggressive behavior in intracranial DAVFs, and its optimal cutoff value was 1.63 with high sensitivity and specificity for predicting aggressive behavior (area under the curve, 0.909).


The first three-dimensional structure of phosphofructokinase from Saccharomyces cerevisiae determined by electron microscopy of single particles.
Phosphofructokinaseis a key regulatory enzyme of the glycolytic pathway. We have determined the structure of this enzyme from Saccharomyces cerevisiae to a resolution of 2.0 nm. This is the first structure available for this family of enzymes in eukaryotic organisms. Phosphofructokinase is an octamer composed of 4alpha and 4beta subunits arranged in a dihedral point group symmetry D(2). The enzyme has a very open and elongated structure, with dimensions of 24 nm in length and 17 nm in width. The final structure, calculated from 0 degrees tilt projections of the molecule at random orientations using as reference the volume obtained by the random conical reconstruction technique in ice, has allowed us to discern the shapes of the subunits and their mutual arrangement in the octamer.


Plasma fat-soluble vitamin and carotenoid concentrations after plant sterol and plant stanol consumption: a meta-analysis of randomized controlled trials.
Plant sterols and stanols interfere with intestinal cholesterol absorption, and it has been questioned whether absorption and plasma concentrations of fat-soluble vitamins and carotenoids are also affected. We conducted a meta-analysis to assess the effects of plant sterol and stanol consumption on plasma fat-soluble vitamin and carotenoid concentrations. Forty-one randomized controlled trials involving 3306 subjects were included. Weighted absolute and relative changes of non-standardized and total cholesterol (TC)-standardized values (expressed as summary estimates and 95 % CIs) were calculated for three fat-soluble vitamins (α- and γ-tocopherol, retinol and vitamin D) and six carotenoids (β-carotene, α-carotene, lycopene, lutein, zeaxanthin and β-cryptoxanthin) using a random effects model. Heterogeneity was assessed using predefined subject and treatment characteristics. Average plant sterol or stanol intake was 2.5 g/d. Relative non-standardized and TC-standardized concentrations of β-carotene decreased by, respectively, -16.3 % (95 % CI -18.3; -14.3) and -10.1 % (-12.3; -8.0), α-carotene by -14.4 % (-17.5; 11.3) and -7.8 % (-11.3; -4.3), and lycopene by -12.3 % (-14.6; -10.1) and -6.3 % (-8.6; -4.0). Lutein concentrations decreased by -7.4 % (-10.1; -4.8), while TC-standardized concentrations were not changed. For zeaxanthin, these values were -12.9 % (-18.9; -6.8) and -7.7 % (-13.8; -1.7) and for β-cryptoxanthin -10.6 % (-14.3; -6.9) and -4.8 % (-8.7; -0.9). Non-standardized α-tocopherol concentrations decreased by -7.1 % (-8.0; -6.2) and γ-tocopherol by -6.9 % (-9.8; -3.9), while TC-standardized tocopherol concentrations were not changed. Non-standardized retinol and vitamin D concentrations were not affected. Results were not affected by baseline concentrations, dose, duration and type of plant sterols/stanols, except for significant effects of duration (≤4 vs. >4 weeks) on TC-standardized lutein concentrations (1.0 vs. -5.6 %) and type of plant sterol/stanol on TC-standardized β-carotene concentrations (-8.9 vs. -14.2 %). Plant sterol and stanol intake lowers TC-standardized hydrocarbon carotenoid concentrations, differently affects TC-standardized oxygenated carotenoid concentrations, but does not affect TC-standardized tocopherol concentrations or absolute retinol and vitamin D concentrations. Observed concentrations remained within normal ranges.


Lipid changes associated with erythroid differentiation of Friend erythroleukemia cells.
Friend erythroleukemia cells were induced to differentiate by dimethyl sulfoxide (DMSO) and hexamethylene-bis-acetamide (HBMA) in order to investigate whether their lipid characteristics, common to other systems of transformed cells, revert to a normal differentiation pattern. DBA/2 mouse erythrocytes were examined as a model of terminal differentiation in erythroid lineage. Variants of erythroleukemia cells not inducible to erythroid differentiation by DMSO and HMBA were also used in this study, in order to test whether lipid modifications occurring in differentiated erythroleukemia cells were related to the differentiation process or caused by specific effects of the inducers. Friend erythroleukemia cells showed the same lipid characteristics as those found in other transformed cell types. That is, a high level of ether-linked lipids and low percentages of long chain polyunsaturated fatty acids along with an accumulation of monoenoic fatty acids in phospholipids. These lipid characteristics remained unchanged when erythroleukemia cells were induced to differentiation by either DMSO or HMBA. However, other lipid components of erythroleukemia cells, e.g., phosphatidylethanolamine and triglycerides, were affected by erythroid differentiation. There were also changes of some lipid components of erythroleukemia cells, such as cholesteryl esters, which were related to specific effects of the inducers. Both DMSO- and HMBA-resistant variants differed from the inducible erythroleukemia cells, mainly in their ether-linked phospholipid pattern.


In silico-guided identification of potential inhibitors against β2m aggregation in dialysis-related amyloidosis.
In dialysis-related amyloidosis (DRA), misfolding of β2-microglobulin (β2m) leads to amyloid fibril deposition mainly in the skeletal joints seriously affecting their functionality. The identification and characterization of small-molecules that bind β2m and possibly inhibit its aggregation remain unexplored. In the present study, a ligand-based virtual screening approach and molecular dynamics (MD) simulations were employed to explore potent small-molecule inhibitors against β2m aggregation. The compounds were screened from various small-molecule databases by applying ligand-based virtual screening with rifamycin SV (RSV) as a reference compound. The molecular docking analysis was performed to filter out lead compounds with a higher binding affinity than RSV from a library of ∼800 compounds. Three compounds, ChEBI68321 (C1), ChEMBL360190 (C2) and ZINC3091144 (C3), displaying excellent binding free energies of -51.29, -36.51 and -34.36 kcal/mol, respectively, with β2m were subjected to MD simulations to get insights into the binding locations, key interactions and structural stability of the β2m-ligand complexes. The hydrogen bond analysis highlight higher structural stability and reduced flexibility of the loop regions of β2m in presence of C1, C2 and C3. The integrated computational approach employed in the present study identify promising lead compounds against β2m aggregation in DRA. Abbreviationsβ2mβ2-microglobulin3Dthree dimensionalADAlzheimer's diseaseADTAutoDock ToolsDRADialysis-related amyloidosisDSSPdictionary of secondary structure of proteinsFELfree energy landscapeGROMACSGROningen MAchine for Chemical SimulationsLGALamarckian Genetic AlgorithmLINCSLINear Constraint SolverMCmain chainMDmolecular dynamicsMHC-Imajor histocompatibility complex class IMM-PBSAmolecular mechanics Poisson-Boltzmann surface areaPMEnanometer (nm); particle mesh ewaldPCAprincipal component analysisPDBprotein data bankRgradius-of-gyrationRSVrifamycin SVRMSDroot-mean-square deviationRMSFroot-mean-square fluctuationSCside chainSPCsimple point chargeSASASolvent accessible surface areaVMDvisual molecular dynamicsCommunicated by Ramaswamy H. Sarma.


Optimizing Occupations, Habits, and Routines for Health and Well-Being With Lifestyle Redesign®: A Synthesis and Scoping Review.
Lifestyle Redesign® originated as a preventive occupational therapy intervention for healthy older adults, and it was found to be both effective and cost effective in the Well Elderly Studies initiated in the 1990s. Building on that empirical foundation, the scope of Lifestyle Redesign has been greatly expanded as a general intervention framework addressing prevention and chronic condition management in a wide range of populations, settings, and conditions. Yet until now, its full scope, defining characteristics, and supporting evidence have not been clearly and succinctly described, limiting its potential reach and impact. To outline the definition and key characteristics of Lifestyle Redesign, provide a scoping review of its evidence base and future directions for research, describe its current applications, and make recommendations for its use in clinical practice. We searched PubMed and CINAHL, tables of contents of 10 occupational therapy journals, and citations in two seminal Lifestyle Redesign publications to identify articles published in 1997-2020 that described quantitative outcomes (for n ≥ 20) of interventions meeting the defining characteristics of Lifestyle Redesign. Our scoping review yielded 12 publications providing supportive evidence for Lifestyle Redesign's positive impact on a range of health and well-being outcomes among both well populations and those with chronic conditions. Lifestyle Redesign has the potential to meet a growing need in clinical and community settings for health care services that address prevention, health promotion, and chronic disease management. What This Article Adds: Current evidence supports the use of Lifestyle Redesign to improve health and well-being for a range of client populations. This review outlines its defining characteristics and current applications to improve its implementation in clinical practice and expand related research efforts.


Neurological outcome prediction in a cardiorespiratory arrest survivor.
Outcome prediction of neurological recovery in an unconscious survivor of cardiorespiratory arrest is difficult and uncertain. We describe the case of a 25-yr-old post-arrest survivor who made a remarkable neurological improvement despite a seemingly hopeless prognosis. Conventional clinical and neurophysiological assessments need to be interpreted with care in the presence of uncontrolled seizure activity and sedative medications. The measurement of biochemical markers in the serum and cerebrospinal fluid may be useful in helping the clinician to arrive at a more accurate neurological outcome prediction.


Pecuniary compensation increases participation in screening for colorectal cancer.
The participation rate in medical screening programmes is typically below 100%, which means that not all potential health benefits are fully exploited. In this paper, the prospect of pecuniary compensation is tested as a method of increasing the participation rate. We propose a model explaining the individual's probability of participating in screening for colorectal cancer when he is offered pecuniary compensation, given that he did not participate when first invited. The participant's decision is based on both known and uncertain factors. The estimation is conducted in two steps, where a binary probit model is used in each. We find that pecuniary compensation increases the probability of participation, and that an individual's participation probability systematically varies with variables such as travel expenses, income, age, education level, expected benefit from the screening, use of health-care services, genetic predisposition and subjective health status. Using the results from the estimation, we predict changes in the participation rate for different levels of compensation and estimate the cost per additional individual screened. The cost per additional individual screened is 808, including 25 in compensation; this cost increases with the level of compensation.


Structural Characterization of Intact Glycoconjugates by Tandem Mass Spectrometry Using Electron-Induced Dissociation.
Characterizing the structures of glycoconjungates is important because of glycan heterogeneity and structural complexity of aglycon. The presence of relatively weak glycosidic linkages leads to preferential cleavages that limit the acquisition of structural information under typical mass spectrometry dissociation conditions, such as collision-induced dissociation (CID) and infrared multiphoton dissociation. In this paper, we explored the dissociation behaviors of different members of glycoconjugates, including glycopeptides, glycoalkaloids, and glycolipids, under electron-induced dissociation (EID) conditions. Using CID spectra as references, we found that EID is not only a complementary method to CID, but also a method that can generate extensive fragment ions for the structural characterization of all intact glycoconjugates studied. Furthermore, isomeric ganglioside species can be differentiated, and the double bond location in the ceramide moiety of the gangliosides can be identified through the MS3 approach involving sequential CID and EID processes.


Hexafluoroisopropyl Carbamates as Selective MAGL and Dual MAGL/FAAH Inhibitors: Biochemical and Physicochemical Properties.
A series of hexafluoroisopropyl carbamates with indolylalkyl- and azaindolylalkyl-substituents at the carbamate nitrogen was synthesized and evaluated for inhibition of the endocannabinoid degrading enzymes fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL). The synthesized derivatives with butyl to heptyl spacers between the heteroaryl and the carbamate moiety were inhibitors of both enzymes. For investigated compounds in which the alkyl chain was partially incorporated into a piperidine ring, different results were obtained. Compounds with a methylene spacer between the piperidine ring and the heteroaromatic system were found to be selective MAGL inhibitors, while an extension of the alkyl spacer to two to four atoms resulted in dual inhibition of FAAH/MAGL. The only small change in enzyme inhibitory activity with variation of the heteroaromatic system indicates that the reactive hexafluoroisopropyl carbamate group is mainly responsible for the strength of the inhibitory effect of the compounds. Selected derivatives were also tested for hydrolytic stability in aqueous solution, liver homogenate and blood plasma as well as for aqueous solubility and for permeability in a Caco-2 cell model. Some compounds showed a slightly higher MAGL inhibitory effect than the known selective MAGL inhibitor ABX-1431 and also partly surpassed this substance with regard to certain physicochemical and biochemical properties such as water solubility and cell permeability.


Severe sleep problems among infants in a normal population in Sweden: prevalence, severity and correlates.
The aim of this study was to explore the prevalence of parentally experienced infant sleep problems, with special interest in severe problems, in a total community sample of 2518 infants aged 6-18 mo. Correlates to severe sleep problems were sought. The families were approached using a questionnaire and 83% responded. Data from the collection procedure point to a nonselective dropout. Sixteen percent of the parents reported their children as having moderate or severe difficulties in falling asleep at night (sleep refusal, bedtime struggles) and 30% reported frequent night waking. Almost all (93%) of the parents had sought help at the Child Health Centre (CHC), but only 48% were satisfied with the support and advice they got. Severe sleep problems as defined by the ICSD (International Classification of Sleep Disorders, 1990) were found in 129 of the children (6.2%), who were studied in detail, with the rest of the population as controls. Severe sleep problems were found to be correlated with parental worries and anxiety concerning infant health (although the children were reported as being as healthy as the controls), infant feeding problems and intensive parental interventional behaviour (especially feeding) during the evening and night. A common factor of insecurity in the parental role is suggested.


An anti-vascular endothelial growth factor receptor 2/fetal liver kinase-1 Listeria monocytogenes anti-angiogenesis cancer vaccine for the treatment of primary and metastatic Her-2/neu+ breast tumors in a mouse model.
Thirty years after angiogenesis was shown to play an enabling role in cancer, modern medicine is still trying to develop novel compounds and therapeutics to target the tumor vasculature. However, most therapeutics require multiple rounds of administration and can have toxic side effects. In this study, we use anti-angiogenesis immunotherapy to target cells actively involved in forming new blood vessels that support the growth and spread of breast cancer. Targeting a central cell type involved in angiogenesis, endothelial cells, we immunized against host vascular endothelial growth factor receptor 2 to fight the growth of Her-2/neu(+) breast tumors. Using the bacterial vector, Listeria monocytogenes (Lm), we fused polypeptides from the mouse vascular endothelial growth factor receptor 2 molecule (fetal liver kinase-1) to the microbial adjuvant, listeriolysin-O, and used Lm to deliver the Ags and elicit potent antitumor CTL responses. Lm-listeriolysin-O-fetal liver kinase-1 was able to eradicate some established breast tumors, reduce microvascular density in the remaining tumors, protect against tumor rechallenge and experimental metastases, and induce epitope spreading to various regions of the tumor-associated Ag Her-2/neu. Tumor eradication was found to be dependent on epitope spreading to HER-2/neu and was not solely due to the reduction of tumor vasculature. However, vaccine efficacy did not affect normal wound healing nor have toxic side effects on pregnancy. We show that an anti-angiogenesis vaccine can overcome tolerance to the host vasculature driving epitope spreading to an endogenous tumor protein and drive active tumor regression.


Image-Enhanced Capsule Endoscopy Improves the Identification of Small Intestinal Lesions.
Image-enhanced endoscopy is useful for diagnosing and identifying lesions in the gastrointestinal tract. Recently, image-enhanced endoscopy has become a breakthrough technology that has attracted significant attention. This image enhancing technology is available for capsule endoscopy, which is an effective tool for small intestinal lesions and has been applied in flexible spectral color enhancement technology and in contrast capsule like narrow-band imaging. In this field, most researchers focus on improving the visibility and detection of small intestinal lesions. This review summarizes previous studies on image-enhanced capsule endoscopy and aims to evaluate the efficacy of this technology.


The polycystic ovary post-rotterdam: a common, age-dependent finding in ovulatory women without metabolic significance.
The age-specific prevalence of polycystic ovaries (PCO), as defined by the Rotterdam criteria, among normal ovulatory women, has not yet been reported. It is also uncertain whether these women differ from their peers in the hormonal or metabolic profile. A total of 262 ovulatory Caucasian women aged 25-45 yr, enrolled in a community-based ovarian aging study (OVA), underwent transvaginal ultrasound assessment of ovarian volume and antral follicle count (AFC) in the early follicular phase and were categorized as to whether they met the Rotterdam definition of PCO by AFC (≥12 in one ovary) and/or by volume (>10 cm(3) for one ovary). The effect of age on prevalence of PCO was assessed. Serum hormones and metabolic measures were compared between women meeting each element of the Rotterdam criterion and those without PCO using age-adjusted linear regressions. The prevalence of PCO by AFC was 32% and decreased with age. Those with PCO by AFC had lower FSH; higher anti-Müllerian hormone, estrone, dehydroepiandrostenedione sulfate, and free androgen index; and slightly higher total testosterone than those without PCO. However, slightly higher body mass index and waist circumference were the only metabolic differences. Women with PCO by volume had higher anti-Müllerian hormone and free androgen index but did not differ in any other hormonal or metabolic parameter. PCO is a common, age-dependent finding among ovulatory women. These women lack the metabolic abnormalities seen in PCO syndrome. Isolated PCO in an ovulatory woman is not an indication for metabolic evaluation.


[64Cu]Cu-DOTATATE PET metrics in the investigation of atherosclerotic inflammation in humans.
The aim of this study was to assess and compare the arterial uptake of the inflammatory macrophage targeting PET tracer [64Cu]Cu-DOTATATE in patients with no or known cardiovascular disease (CVD) to investigate potential differences in uptake. Seventy-nine patients who had undergone [64Cu]Cu-DOTATATE PET/CT imaging for neuroendocrine neoplasm disease were retrospectively allocated to three groups: controls with no known CVD risk factors (n = 22), patients with CVD risk factors (n = 24), or patients with known ischemic CVD (n = 33). Both maximum, mean of max and most-diseased segment (mds) standardized uptake value (SUV) and target-to-background ratio (TBR) uptake metrics were measured and reported for the carotid arteries and the aorta. To assess reproducibility between different reviewers, Bland-Altman plots were made. For the carotid arteries, SUVmax (P = .03), SUVmds (0.05), TBRmax (P < .01), TBRmds (P < .01), and mean-of-max TBR (P = .01) were overall shown to provide a group-wise difference in uptake. When measuring uptake values in the aorta, a group-wise difference was only observed with TBRmds (P = .04). Overall, reproducibility of the reported uptake metrics was excellent for SUVs and good to excellent for TBRs for both the carotid arteries and the aorta. Using [64Cu]Cu-DOTATATE PET imaging as a marker of atherosclerotic inflammation, we were able to demonstrate differences in some of the most frequently reported uptake metrics in patients with different degrees of CVD. Measurements of the carotid artery as either maximum uptake values or most-diseased segment analysis showed the best ability to discriminate between the groups.


Effect of captopril on renal hemodynamics and renal prostaglandins in early type II diabetic patients with normo-or microalbuminuria.
In this study, we investigated the effect of captopril (CPT) on glomerular filtration rate (GFR), effective renal plasma flow (ERPF), filtration fraction (FF), urinary albumin excretion (UAE) and daily urinary excretion of thromboxane B2 (TXB2) and 6-keto- prostaglandin F1a (6-keto-PGF1a) in 29 normotensive non-insulin-dependent diabetes (NIDDM) patients without clinically discernible nephropathy. Before treatment, urinary excretion 6-keto-PGF1a was significantly increased (P < 0.05) in 29 NIDDM patients compared with 25 health subjects matched for age and sex. The values of GFR and FF were significantly higher (P < 0.01 and P < 0.005, respectively) in NIDDM than in normal volunters, whereas ERPF was comparable in both groups. Meanwhile we observed that UAE of early NIDDM was increased before treatment. After CPT treatment, GFR, FF, UAE and urinary excretion of 6-keto-PGF1a were significantly reduce (all P < 0.005) compared with those of NIDDM before treatment. These data indicated that CPT is effective in lowering glomerular filtration pressure and ameliorating microalbuminuria in the normotensive early NIDDM.


Differentiation and treatment of anemia in HIV disease.
Anemia is a frequent complication of HIV disease that contributes to decreased quality of life and increased morbidity and mortality. The three major categories of anemia in HIV disease are anemia due to impaired red blood cell production, anemia due to increased red blood cell destruction, and anemia due to increased red blood cell loss. Although anemia of chronic illness is the most common type of anemia in HIV disease, other classifications of anemia may be encountered. Understanding the pathophysiology of anemia and laboratory tests that are frequently used to establish the differential diagnosis of anemia helps to ensure that HIV-infected individuals will receive appropriate treatment.


K562 cell strains differ in their response to poliovirus infection.
Poliovirus readily establishes a persistent infection in the K562-Mu erythroleukemia cell strain. In this study, three additional K562 cell strains were analyzed for their responses to poliovirus infection and found to be quite variable. K562 cells obtained from the ATCC established a persistent infection, similar to the K562-Mu cell strain, while the majority of cells from two other strains, K562-KI and K562-We, were killed by 4 or 11 days postinfection (p.i.), respectively. Several characteristics of the uninfected and infected cell strains were examined to determine if differences existed which could explain the dramatically different responses to infection. Since K562 cell strains can differentiate toward several cell lineages, the four strains were analyzed for physical and functional likeness to the original K562 cell line using well-established functional criteria to determine whether gross changes in differentiation state had occurred. Based on the lack of MHC class I antigen expression and a dose-dependent increase in globin synthesis in response to hemin, all three laboratory K562 cell strains were indistinguishable from the ATCC reference strain. Surface poliovirus receptor levels were also similar in all K562 cell strains, although four- to fivefold lower than those in HeLa cells. Most biochemical events in virus replication either were very similar among K562 cells or were slightly variable and did not correlate with the degree of cell killing. These included levels of virus production, levels of viral protein produced, and processing and turnover of viral polypeptides. The key difference between the cell strains which consistently correlated with cell killing was the degree of virus-induced host translation shutoff, which was always greatest in the most virus-sensitive K562-KI cells. In addition, levels of 2Apro produced in K562 cell strains did not appear to correlate with the levels of host protein shutoff. A related and novel finding in these studies which also strongly correlated with the outcome of infection was the ability of levels of intact p220 to recover by 24 hr p.i. in virus-resistant K562-Mu and -ATCC cells. These data suggest that the key determinants of outcome of infection in this cell model are cytoplasmic host factors related to cytopathology and not factors which may modulate levels of viral protein synthesis or RNA synthesis.


A Phase Field Technique for Modeling and Predicting Flow Induced Crystallization Morphology of Semi-Crystalline Polymers.
Flow induced crystallization of semi-crystalline polymers is an important issue in polymer science and engineering because the changes in morphology strongly affect the properties of polymer materials. In this study, a phase field technique considering polymer characteristics was established for modeling and predicting the resulting morphologies. The considered crystallization process can be divided into two stages, which are nucleation upon the flow induced structures and subsequent crystal growth after the cessation of flow. Accordingly, the proposed technique consists of two parts which are a flow induced nucleation model based on the calculated information of molecular orientation and stretch, and a phase field crystal growth model upon the oriented nuclei. Two-dimensional simulations are carried out to predict the crystallization morphology of isotactic polystyrene under an injection molding process. The results of these simulations demonstrate that flow affects crystallization morphology mainly by producing oriented nuclei. Specifically, the typical skin-core structures along the thickness direction can be successfully predicted. More importantly, the results reveal that flow plays a dominant part in generating oriented crystal morphologies compared to other parameters, such as anisotropy strength, crystallization temperature, and physical noise.


Is it possible to make a reliable prognosis within the first hour of life for very low birth weight infants delivered after preterm premature rupture of membranes?
One third of all preterm births are due to preterm premature rupture of membranes (pPROM). An accurate prognostic evaluation after admission to the neonatal intensive care unit is necessary. The aim of this study was to identify prognostic factors within the first hour of life for mortality, short-term pulmonary morbidity, chronic lung disease (CLD) and severe cerebral morbidity in very low birth weight (VLBW) infants after pPROM. This retrospective study included 300 infants with pPROM who fit the study criteria and were derived from a cohort of 1,435 VLBW infants. A total of 17 obstetric and neonatal factors were evaluated by univariate and multivariate analysis. Gestational age at birth and 5-min Apgar score correlated significantly with all 4 outcomes. The results of the first blood gas analysis correlated with 3 outcomes and the first mean arterial pressure with 2 outcomes. Anhydramnios and a lower number of courses of antenatal steroids correlated with higher mortality, and preterm labor correlated with CLD. The multivariate analysis revealed gestational age, 5-min Apgar score, the results of the first blood gas analysis, the first mean arterial pressure and anhydramnios to be significant predictors. The positive predictive value ranged from 20 to 81%, and the negative predictive value ranged from 79 to 92%. Gestational age at birth and parameters reflecting postnatal adaptation were the most precise factors for assessment of the prognosis of VLBW infants after pPROM within the first hour of life. Apart from anhydramnios, obstetric factors did not predict neonatal outcome. At 1 h of age, our models of perinatal risk factors were more effective in predicting a favorable outcome than an adverse outcome.


[Formalization of criteria of a patient dismissal after performance of operative intervention under general anaesthesia in the one day stationary environment].
Modern anaesthesiological management of operative intervention is characterized by high level of prognostication and safety for the patient. It was achieved due to application of a new pharmacological preparations, used for general anaesthesia and the improvement of technical armament and systemic approach to the problem of the patients safeness during anaesthesia conduction. These factors constitute the base for developing of the one day stationaries net. Application of modern medical technologies permits to perform operative intervention under general anaesthesia and to dismiss the patient during one day. Today there the necessity formed to elaborate, to systemize and to formalize the criterions of safety dismiss of the patient after performance of operative intervention under general anaesthesia in conditions of a one day stationary.


Quassidines A-D, bis-beta-carboline alkaloids from the stems of Picrasma quassioides.
Four new bis-beta-carboline alkaloids, quassidines A-D (1-4), together with a known alkaloid, picrasidine C (5), were isolated from the stems of Picrasma quassioides. Quassidine A (1) is the first reported bis-beta-carboline alkaloid possessing a novel cyclobutane moiety. The structures of the new compounds were determined on the basis of their 1D and 2D NMR and X-ray diffraction data. A possible biogenetic pathway for these alkaloids was proposed, and all compounds were evaluated for anti-inflammatory activity. Only quassidine A (1) showed weak activity.


Topical use of antifibrinolytic agent to reduce postoperative bleeding after coronary artery bypass surgery.
Antifibrinolytic agents reduce bleeding after cardiac surgery, but there are adverse effects after their systemic use. These effects are avoided by topical application of antifibrinolytic agents in pericardial cavity. We compared the effects of topically applied epsilon-aminocaproic acid (EACA) and placebo on postoperative bleeding and transfusion requirements after coronary artery bypass surgery. In this single center prospective, randomized, double-blind trial, 53 patients were randomized into two groups to receive EACA (24 g in 250 ml of saline solution) or placebo (250 ml of saline solution) before sternal closure. Groups were comparable with respect to all preoperative and intraoperative variables. Postoperative bleeding, transfusion requirements and hematologic parameters were evaluated. Postoperative bleeding within first 24 hours (h) period (EACA group 154.66+/-74.64 x Placebo group 220.21+/-136.42 ml; P=0.031) showed statistically significant inter-group difference, within 48 h (EACA group 259.14+/-420.07 x Placebo group 141.67+/-142.58 ml; P=0.614), as well as cumulative blood loss (EACA group 832.07+/-576.86 x Placebo group 827.50+/-434.12 ml; P=0.975), not showed statistically inter-group differences. Inter-group difference of blood product requirements was statistically significant (EACA group 185.90+/-342.07 x Placebo group 439.42+/-349.07 ml; P=0.016). Laboratory analyses showed no differences between the two groups postoperative (hematologic characteristics: hemoglobin (g/dl)- EACA group 9.18+/-0.92 x Placebo group 8.85+/-1.48 g/dL; P=0.11; hematocrit (%)-EACA group 28.15+/-3.35 x Placebo group 26.67+/-4.15%; P=0.06). Topical use of epsilon aminocaproic acid reduces postoperative bleeding in the first 24 hours and requirements of blood transfusion after coronary artery bypass graft surgery.


Neurocognitive outcomes in children following immersion: a long-term study.
To investigate long-term neurocognitive outcomes after a near-drowning incident in children who were deemed neurologically intact on discharge from hospital. A prospective cohort study of near-drowning children. 95 drowning and near-drowning admissions, 0-16 years of age, from January 2009 to December 2013, to The Children's Hospital at Westmead, Sydney, NSW, Australia. 23 children both met the criteria and had parental consent for the study. Identification of the long-term deficits in behaviour, executive function, motor skills, communicative skills and well-being over a 5-year period. Assessment was undertaken at 3-6 months, 1 year, 3 years and 5 years after near-drowning at clinic visits. Physical developmental screening and executive function screening were done using Behavior Rating Inventory of Executive Function-Preschool version (BRIEF-P) and BRIEF. 95 drowning and near-drowning episodes occurred during the study period. 10 (11%) children died, 28 were admitted to the paediatric intensive care unit and 64 directly to a ward. 3 children died in emergency department, 7 children had severe neurological deficit on discharge from the hospital. 23 were subsequently recruited into the study; 5 (22%) of these children had abnormalities in behaviour and/or executive function at some during their follow-up. Children admitted to hospital following a near-drowning event warrant long-term follow-up to identify any subtle sequelae which might be amenable to intervention to ensure optimal patient outcome.


Long-term effectiveness of nonpharmacological treatment of hypertension.
Various nonpharmacological therapies reduce the blood pressure of a significant portion of both patients with established hypertension and people who are considered to be at high risk for the development of hypertension; that is, they are secondary and primary preventions. Of the various therapies, weight reduction, sodium restriction, moderation of alcohol intake, and regular aerobic exercise have been shown to be most effective, whereas the effectiveness of other practices has been less uniform or smaller in degree. Changes in lifestyle, mainly involving diet and physical activity, should be widely used to treat and, hopefully, to prevent hypertension.


Linguistic approach for identification of medication names and related information in clinical narratives.
Pharmacotherapy is an integral part of any medical care process and plays an important role in the medical history of most patients. Information on medication is crucial for several tasks such as pharmacovigilance, medical decision or biomedical research. Within a narrative text, medication-related information can be buried within other non-relevant data. Specific methods, such as those provided by text mining, must be designed for accessing them, and this is the objective of this study. The authors designed a system for analyzing narrative clinical documents to extract from them medication occurrences and medication-related information. The system also attempts to deduce medications not covered by the dictionaries used. Results provided by the system were evaluated within the framework of the I2B2 NLP challenge held in 2009. The system achieved an F-measure of 0.78 and ranked 7th out of 20 participating teams (the highest F-measure was 0.86). The system provided good results for the annotation and extraction of medication names, their frequency, dosage and mode of administration (F-measure over 0.81), while information on duration and reasons is poorly annotated and extracted (F-measure 0.36 and 0.29, respectively). The performance of the system was stable between the training and test sets.


Early Recurrence Patterns Following Totally Intracorporeal Robot-assisted Radical Cystectomy: Results from the EAU Robotic Urology Section (ERUS) Scientific Working Group.
Recurrence following radical cystectomy often occurs early, with >80% of recurrences occurring within the first 2 yr. Debate remains as to whether robot-assisted radical cystectomy (RARC) negatively impacts early recurrence patterns because of inadequate resection or pneumoperitoneum. We report early recurrence patterns among 717 patients who underwent RARC with intracorporeal urinary diversion at nine different institutions with a minimum follow-up of 12 mo. Clinical, pathologic, radiologic, and survival data at the latest follow-up were collected. Recurrence-free survival (RFS) estimates were generated using the Kaplan-Meier method, and Cox regression models were built to assess variables associated with recurrence. RFS at 3, 12, and 24 mo was 95.9%, 80.2%, and 74.6% respectively. Distant recurrences most frequently occurred in the bones, lungs, and liver, and pelvic lymph nodes were the commonest site of local recurrence. We identified five patients (0.7%) with peritoneal carcinomatosis and two patients (0.3%) with metastasis at the port site (wound site). We conclude that unusual recurrence patterns were not identified in this multi-institutional series and that recurrence patterns appear similar to those in open radical cystectomy series. In this multi-institutional study, bladder cancer recurrences following robotic surgery are described. Early recurrence rates and locations appear to be similar to those for open radical cystectomy series.


Emerging Biological Principles of Metastasis.
Metastases account for the great majority of cancer-associated deaths, yet this complex process remains the least understood aspect of cancer biology. As the body of research concerning metastasis continues to grow at a rapid rate, the biological programs that underlie the dissemination and metastatic outgrowth of cancer cells are beginning to come into view. In this review we summarize the cellular and molecular mechanisms involved in metastasis, with a focus on carcinomas where the most is known, and we highlight the general principles of metastasis that have begun to emerge.


[Diagnostic problems of hematological disorder using automated blood cell analyzer].
Although an automated blood cell counter provides the different test results to the clinician both precisely and rapidly, confusing data have also been reported which caused much confusion for the diagnosis of diseases. We investigated five different automated instruments using blood samples from different patients with hematological disorders to evaluate the flow of these automated counters in the interpretation of test results. Platelet aggregation, hemolysis and cryoglobulin can influence the evaluation with such automated instruments. The degree of the variance is different between false value and corrected value. Furthermore, cryoglobulin may give false data on coagulation and fibrinolysis tests. Automated white cell differentiation is based upon flow system or pattern recognition, but overlooking of the abnormal cells cannot be avoided by either method, such as a small number of blasts, atypical lymphocytes, adult T-cell leukemia cell, etc. Therefore, it is necessary of the bases is blood cell to the CD4/CD8 measurement and microscopic check along with considering biochemical parameters. We should make smears from such patients. For analysis of surface markers of hematological malignancy cell by flow cytometry proper selection of antibodies and setting of gate are required. To prevent mistakes due to morphological misinterpretation or other unsuitable conditions, we should thoroughly understand the morphologic aspects of leukemia cells.


SVM and SVR-based MHC-binding prediction using a mathematical presentation of peptide sequences.
At present, there are a number of methods for the prediction of T-cell epitopes and major histocompatibility complex (MHC)-binding peptides. Despite numerous methods for predicting T-cell epitopes, there still exist limitations that affect the reliability of prevailing methods. For this reason, the development of models with high accuracy are crucial. An accurate prediction of the peptides that bind to specific major histocompatibility complex class I and II (MHC-I and MHC-II) molecules is important for an understanding of the functioning of the immune system and the development of peptide-based vaccines. Peptide binding is the most selective step in identifying T-cell epitopes. In this paper, we present a new approach to predicting MHC-binding ligands that takes into account new weighting schemes for position-based amino acid frequencies, BLOSUM and VOGG substitution of amino acids, and the physicochemical and molecular properties of amino acids. We have made models for quantitatively and qualitatively predicting MHC-binding ligands. Our models are based on two machine learning methods support vector machine (SVM) and support vector regression (SVR), where our models have used for feature selection, several different encoding and weighting schemes for peptides. The resulting models showed comparable, and in some cases better, performance than the best existing predictors. The obtained results indicate that the physicochemical and molecular properties of amino acids (AA) contribute significantly to the peptide-binding affinity.


Advanced patient transfer assist device with intuitive interaction control.
This research aims to improve patient transfers by developing a new type of advanced robotic assist device. It has multiple actuated degrees of freedom and a powered steerable base to maximize maneuverability around obstacles. An intuitive interface and control strategy allows the caregiver to simply push on the machine in the direction of desired patient motion. The control integrates measurements of both force and proximity to mitigate any potential large collision forces and provides operators information about obstacles with a form of haptic feedback. Electro-hydraulic pump controlled actuation provides high force density for the actuation. Nineteen participants performed tests to compare transfer operations (transferring a 250-lb mannequin between a wheelchair, chair, bed, and floor) and interaction control of a prototype device with a commercially available patient lift. The testing included a time study of the transfer operations and subjective rating of device performance. The results show that operators perform transfer tasks significantly faster and rate performance higher using the prototype patient transfer assist device than with a current market patient lift. With further development, features of the new patient lift can help facilitate patient transfers that are safer, easier, and more efficient for caregivers.


Efficacy and complications of polyethylene glycols for treatment of constipation in children: a meta-analysis.
Constipation is a common childhood complaint. In 90% to 95% of children, constipation is functional, which means that there is no objective evidence of an underlying pathological condition. Polyethylene glycol (PEG or macrogol) solution is an osmotic laxative agent that is absorbed in only trace amounts from the gastrointestinal tract and routinely used to treat chronic constipation in adults. Here, we report the results of a meta-analysis of PEG-based laxatives compared with lactulose, milk of magnesia (magnesium hydroxide), oral liquid paraffin (mineral oil), or acacia fiber, psyllium fiber, and fructose in children. This meta-analysis was conducted in accordance with PRISMA guidelines and involved searches of MEDLINE, Cochrane, EMBASE, and Google Scholar databases up to February 10, 2014, using the keywords (Constipation OR Functional Constipation OR Fecal Impaction) AND (Children) AND (Polyethylene Glycol OR Laxative). Primary efficacy outcomes included a number of stool passages/wk and percentage of patients who reported satisfactory stool consistency. Secondary safety outcomes included diarrhea, abdominal pain, nausea or vomiting, pain or straining at defecation, bloating or flatulence, hard stool consistency, poor palatability, and rectal bleeding. We identified 231 articles, 27 of which were suitable for full-text review and 10 of which were used in the meta-analysis. Patients who were treated with PEG experienced more successful disimpaction compared with those treated with non-PEG laxatives. Treatment-related adverse events were acceptable and generally well tolerated. PEG-based laxatives are effective and safe for chronic constipation and for resolving fecal impaction in children. Children's acceptance of PEG-based laxatives appears to be better than non-PEG laxatives. Optimal dosages, routes of administration, and PEG regimens should be determined in future randomized controlled studies and meta-analyses.


Harmful effects of metal(loid) oxide nanoparticles.
The incorporation of nanomaterials (NMs), including metal(loid) oxide (MOx) nanoparticles (NPs), in the most diversified consumer products, has grown enormously in recent decades. Consequently, the contact between humans and these materials increased, as well as their presence in the environment. This fact has raised concerns and uncertainties about the possible risks of NMs to human health and the adverse effects on the environment. These concerns underline the need and importance of assessing its nanosecurity. The present review focuses on the main mechanisms underlying the MOx NPs toxicity, illustrated with different biological models: release of toxic ions, cellular uptake of NPs, oxidative stress, shading effect on photosynthetic microorganisms, physical restrain and damage of cell wall. Additionally, the biological models used to evaluate the potential hazardous of nanomaterials are briefly presented, with particular emphasis on the yeast Saccharomyces cerevisiae, as an alternative model in nanotoxicology. An overview containing recent scientific advances on cellular responses (toxic symptoms exhibited by yeasts) resulting from the interaction with MOx NPs (inhibition of cell proliferation, cell wall damage, alteration of function and morphology of organelles, presence of oxidative stress bio-indicators, gene expression changes, genotoxicity and cell dead) is critically presented. The elucidation of the toxic modes of action of MOx NPs in yeast cells can be very useful in providing additional clues about the impact of NPs on the physiology and metabolism of the eukaryotic cell. Current and future trends of MOx NPs toxicity, regarding their possible impacts on the environment and human health, are discussed. KEY POINTS: • The potential hazardous effects of MOx NPs are critically reviewed. • An overview of the main mechanisms associated with MOx NPs toxicity is presented. • Scientific advances about yeast cell responses to MOx NPs are updated and discussed.


[Subsets of CD8+ T cells in longterm asymptomatic vertically HIV-1 infected children].
HIV-infection has distinct patterns of disease progression with heterogeneous manifestations. We analyzed the subsets of CD8+ T cells in a group of long term asymptomatic (LTA) HIV-1-infected children who had stable CD4+ T cell counts (> 600/l). Cross-sectional study in HIV-1-vertically infected children older than 7 years who were rated into two groups according to the clinical and immunological classification: a) LTA: 7 asymptomatic HIV-1-infected children in A1, and b) rapid progressor (PR): 14 age-matched C3 HIV-1-infected children. Controls included 17 age-matched uninfected children. Characterization of CD8+ T-cell subsets was done by three-color flow cytometry. LTA children displayed similar values of memory CD8+ T cells (CD8+CD45RO+, CD8+CD45RA-CD28+, CD8+ CD45RA-CD62L+) as controls but lower than PR children. LTA patients also showed similar values of naïve CD8+ T cells (CD8+CD45RA+CD62L+, CD8+CD45RA+CD28+, CD8+CD45RA+, CD8+CD28+ and CD8+CD62L+) as controls but higher values than PR children. The values of CD8+CD38+ T cells were similar in LTA and controls but lower in PR. However, LTA children had higher values of CD8+HLA-DR+CD38+ and CD8+HLA-DR+ T cells than controls. Additionally, LTA patients had higher values of pre-effector CD8+ T cells than controls yet the values of effector CD8+ T-cells were similar in both LTA and controls. Moreover, the LTA group had lower values of CD8+CD11b+ T cells than controls. Asymptomatic HIV-1 infected children have an almost normal CD8+ subset distribution, with the exception of activated and pre-effector CD8+ T cells which were higher.


Cherokee self-reliance.
This qualitative study was conducted using ethnography to identify how (a) self-reliance is conceptualized by the Cherokee; (b) the adult male Cherokee perceives, achieves, and demonstrates self-reliance; and (c) nurses can incorporate the Cherokee concept of self-reliance into health care of the Cherokee. The goal of self-reliance was included in the following mission statement of the 1976 Cherokee Nation constitution: "The mission of the government of the Cherokee Nation is to promote and sustain the self-reliance of its members" (Resolution No. 28-85, 1976). The conceptualization and perspective of self-reliance by the Cherokee must be understood to assist effectively in the development and promotion of self-reliance in the Cherokee, especially the male Cherokee. The cultural domain of self-reliance that emerged from the data is a composite of three categories that include being responsible, being disciplined, and being confident. Cutting across all three categories are the two themes of being true to onself and being connected.


Unusual thalamic inclusions in an infant with progressive neurologic dysfunction and blindness.
A 25-month-old boy had a progressive neurologic disorder which started at two months of age and was characterized by seizures, blindness, partial deafness and severe hypotonic quadriparesis. Neuropathologic examination demonstrated the presence of intracytoplasmic neuronal inclusions which were entirely restricted to the thalamus. The inclusions had the histochemical staining characteristics of a glycolipid, were autofluorescent, and ultrastructurally consisted of concentric and parallel arrays of double membranes and curvilinear profiles. These features suggest that the infant may have had a disorder related to neuronal ceroid lipofuscinosis. Review of the literature failed to disclose a similar case.