A manic-depressive symptom self-report in optical scanable format.
The Internal State Scale (ISS) is a self-report instrument that allows the simultaneous assessment of both manic and depressive symptoms in individuals with manic-depressive disorder. Prior work indicates that subscales are highly correlated with clinician ratings of mania and depression and provide a discriminant function that identifies individuals in manic/hypomanic, mixed, depressed, and euthymic mood states. A drawback to the ISS is that its items were developed in the visual analogue scale (VAS) format which is labor-intensive to score, particularly with repeat (e.g. daily) administration. A Likert-based format would allow quick and easy optical scanning for which scoring could be automated. To compare discriminating properties in Likert versus VAS format we re-analyzed previously collected data and collected new data: (a) VAS-based ISS scores from 86 subjects from a prior four-site study were re-analyzed by collapsing scores into 20 and then 10 Likert-based bins to assess loss of precision from collapsing scores, and (b) 24 additional subjects were administered the ISS in VAS and Likert formats to assess loss of precision due to instrument completion factors. Discriminant ability, including kappas and receiver operator characteristic curves, were unchanged across the two formats. Within-subjects reliability was uniformally high across formats. Likert-based scoring of the ISS can be used without loss of precision, thus making automated scoring of the ISS feasible. This format will be particularly useful for studies that require processing of large numbers of ISSs, such as those that collect frequent ratings over long periods of time and/or those that utilize large samples.


Antibody-independent activation of the classical pathway of complement by Epstein-Barr virus.
A purified preparation of Epstein-Barr virus (EBV) has been shown to activate the classical complement pathway by direct interaction with the first component of complement, C1, without the intervention of antibody. No evidence was found for activation of the alternative pathway. Following classical pathway activation the specific affinity of EBV for B cells can be presumed to be lost since the virus will become opsonized for clearance by phagocytic cells bearing complement receptors, CR1 and CR3. This activation is further evidence that complement plays a role in defence mechanisms independently of antibody activity.


Increased levels of interleukin-6 in seminal plasma of infertile men.
The presence of various cytokines, namely the tumor necrosis factor (TNF-alpha), interferon (IFN-gamma), and interleukins (IL-1 beta and IL-6), was investigated in seminal plasma of fertile, infertile, and immunoinfertile men using specific immunoradiometric assays. TNF-alpha and IL-1 beta were not detected. IFN-gamma was detected, but the differences between the levels of fertile and infertile/immunoinfertile were not significant (P > 0.05). IL-6 was detected in seminal plasma with significantly higher levels in infertile/immunoinfertile men compared to those of fertile men. IL-6 was also present in sera, and interestingly, the levels in sera were lower than those in seminal plasma. IL-6 levels in seminal plasma correlated significantly with some sperm parameters and penetration rates in the human sperm penetration assay (SPA). These findings suggest that IL-6 is associated with infertility and may be of importance in specific diagnosis and treatment of male infertility.


MELD-Path Efficiently Computes Conformational Transitions, Including Multiple and Diverse Paths.
The molecular actions of proteins occur along reaction coordinates. Current computer methods have limited ability to explore them. We describe a fast protocol called MELD-path that (1) efficiently samples relevant conformational states via MELD, an accelerator of Molecular Dynamics (MD), (2) seeds multiple short MD trajectories from MELD states, and then (3) constructs Markov State Models (MSM) that give the routes and kinetics. We tested the method against extensive (multi μs) MD simulations of the right-handed- to left-handed-helix transition of a 9-mer peptide of AIB, the symmetry of which allows us to establish convergence. MELD-path finds all the metastable states, their correct relative populations, and the full ensemble of routes, not just a single assumed route. For this transition, we find a very broad route structure. MELD-path is highly parallelizable and efficient, yielding the full route map in a few days of computation. We believe MELD-path could be a general and rapid way to explore mechanistic processes in biomolecules on the computer.


Liponeurofibroma: Clinicopathological features and histogenesis.
A neurofibroma is a common cutaneous benign tumor of neural origin. Various histological variants have been reported. Recently, sporadic reports of fatty variants have been reported but their clinicopathological features have not been well studied. The purpose of this study was to examine liponeurofibroma, and to report the distinctive clinicopathological features and histogenesis in comparison with the classic form. A retrospective study was performed on 130 cases. Immunohistochemical staining was performed for S100, factor VIIIa, perilipin and vascular endothelial growth factor. Masson's trichrome stain was also used. Intratumoral adipocytes were examined with transmission electron microscopy. Thirty-two (24.6%) cases were classified as liponeurofibroma on microscopic examination. This variant was more common in patients with neurofibromatosis type 1, older age and female sex. The most prevalent location was the head and neck. Intratumoral fat deposits showed differences in morphology and size compared with subcutaneous fat on light microscopy. Neurofibromatosis type 1 had the highest odds of fatty change in liponeurofibroma. In sporadic cases, fatty change can be caused by senescence, chronic injury, or tissue hypoxia secondary to internal or external stimuli. Further investigation is needed to identify the pathomechanism of fatty change in various cutaneous neoplasms, including neurofibroma.


Comparison of p38MAPK (mitogene activated protein kinase), p65 NFkappaB (nuclear factor kappa b) and EMMPRIN (extracellular matrix metalloproteinase inducer) expressions with tumor grade and stage of superficial and invasive bladder tumors.
To identify the molecular mechanisms of bladder cancer invasion pathophysiology. To assess EMMPRIN, p65NFkappaB and p38MAPK expressions which play a role in signal transmission system of muscle and non muscle invasive bladder tumors. Fifty-seven patients with non muscle invasive tumors (mean age 65.2 +/- 16.1) and 34 patients with muscle invasive tumors (mean age 62.2 +/- 20.7) were included in this study. Normal tissue from the same patients' bladders were used as control group. Patients had either TUR or radical cystectomy and paraffin sections were prepared for immunohistochemistry. Expression density was evaluated semiquantitively according to tumor grade and invasion depth. Results were compared with Mann Whitney U, Wilcoxon W, Chi Square and variation analysis tests. MAPK and EMMPRIN expression was increased according to tumor grade (p < 0.05). These expressions were also significantly higher in muscle invasive tumors than in non muscle invasive ones (p < 0.05). In normal tissue samples of both TUR and radical cystectomy materials, EMMPRIN, NFkappaB and MAPK expressions were lower than in tumor samples (p < 0.05). NFkappaB wasn't related to tumor grade/stage (p > 0.05). It can be stated that MAPK and EMMPRIN expression is related to the grade of bladder tumor and that NFkappaB positivity is not related to the grade/stage of the disease. In future positivity of lymph nodes and visceral metastasis and survival must be assessed to define the relationship with the expressions in long term follow up studies involving a larger number of patients.


High-level cerebellar expression of cytokines and adhesion molecules in fatal, paediatric, cerebral malaria.
Although the roles played by systemic tumour necrosis factor (TNF) and interleukin 1beta (IL-1beta), and their upregulation of intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1) and E-selectin, in the pathogenesis of human cerebral malaria (CM) are well established, the role of local cytokine release, in the brain, remains unclear. Immunohistochemistry was therefore used to compare the expression of ICAM-1, VCAM-1, E-selectin, IL-1beta, TNF and transforming growth factor beta (TGF-beta) at light-microscope level, in cryostat sections of cerebral, cerebellar and brainstem tissues collected, post-mortem, from Ghanaian children. Among the 21 children investigated were 10 cases of CM, five of severe malarial anemia (SMA), one of purulent bacterial meningitis (PBM), two of non-central-nervous-system infection (NCNSI) and three children who had no infection (NI) when they died. Parasitised erythrocytes were detected in all of the sections from the cases of fatal malaria (CM and SMA), and sequestered leucocytes were present in most of the sections from the CM cases (but none of the sections from the SMA cases). Significantly elevated vascular expression of all three adhesion molecules investigated was detected in the brains of the 15 cases of fatal malaria and one of the cases of NCNSI (a child with Salmonella septicaemia), and in the malaria cases this showed highly significant co-localization with the areas of erythrocyte sequestration. In terms of the levels of expression of ICAM-1, VCAM-1 and E-selectin, there were, however, negligible differences between the CM and SMA cases. Although TGF-beta showed intravascular and perivascular distribution in all the subjects, its expression was most intense in the PBM case and the CM group. Only in the sections from the PBM and CM cases did TNF and IL-1beta show prominent brain parenchymal staining, in addition to the intravascular and perivascular staining seen in all subjects. The highest observed expression of each of the six antigens studied was in the cerebellar sections of the malaria cases. Endothelial activation in the brain therefore appears to be a feature of fatal malaria and Salmonella sepsis, and in cases of fatal malaria is closely associated with leucocyte sequestration. In the present study, IL-1beta and TNF were only up-regulated in the brains of children with neurodegenerative lesions, whereas TGF-beta was present in all cases.


City's racial composition shapes treatment center characteristics and services.
We assessed the extent to which a city's racial composition shapes the characteristics of substance abuse treatment centers. We utilized both the 2004 National Survey of Substance Abuse Treatment Services, which provides information on treatment center characteristics such as availability of comprehensive substance abuse evaluation, and 2000 Census data on the percentage of African Americans and Latinos in a city. We found that a city's racial composition influences treatment center characteristics and services available, but the pattern is complex in that there are inequalities in treatment for certain types of services but not in others. For instance, cities with high percentages of Latinos and African Americans provide more treatment options, such as employment and domestic violence counseling or programs for gay/lesbian clients. However, minority cities have fewer integrated treatment centers that provide comprehensive assessment for substance abuse and mental health problems. We discuss the implications of these findings for service providers, especially those working with Latino and African American clients, as well as provide avenues for future research.


Noninvasive positive airway pressure and risk of myocardial infarction in acute cardiogenic pulmonary edema: continuous positive airway pressure vs noninvasive positive pressure ventilation.
The addition of both noninvasive continuous positive airway pressure (n-CPAP) or noninvasive intermittent positive pressure ventilation (n-IPPV) to medical treatment has been shown to improve the outcome of patients with acute cardiogenic pulmonary edema (ACPE). Previous studies indicated a potential risk of new-onset acute myocardial infarction (AMI) associated with the use of n-IPPV. Although further studies did not confirm this observation, a few recent metaanalyses could not eliminate all the doubts at this regards because of the paucity of data available and the presence of confounding factors. This study aims to assess whether the application of n-IPPV, as opposed to n-CPAP, increases the rate of AMI in ACPE patients. Fifty-two patients with severe hypoxemia consequent to ACPE were randomized to receive n-CPAP (n = 27) or n-IPPV (n = 25) in addition to medical therapy. Patients with signs of acute coronary syndrome on hospital admission were excluded from the study. Cardiac markers, ECG, and clinical/physiologic parameters were assessed at study entry, after 30 and 60 min, and every 6 h for the first 2 days. No significant difference was observed in the rate of AMI (26.9% and 16% with n-CPAP and n-IPPV, respectively, p = 0.244). Rate of intubation (p = 0.481), death (p = 0.662), and hospital stay (p = 0.529) were not different between the two groups. Both techniques were effective in improving gas exchange and vital signs in patients with ACPE. The AMI rate was not different with n-CPAP and n-IPPV, which resulted to be equally effective in the treatment of ACPE. Clinicaltrials.gov Identifier: NCT00453947.


A cathodoluminescence study of the influence of the seed particle preparation method on the optical properties of GaAs nanowires.
Cathodoluminescence at 8 K is used to compare the optical properties of AlGaAs-capped GaAs nanowires, grown by metal-organic vapour phase epitaxy and seeded by gold particles prepared by different methods. Six different methods were used to fabricate and deposit gold seed particles onto GaAs substrates: colloid particles, aerosol particles and particles defined by electron beam lithography. The nanowires were grown with and without an in situ annealing step prior to the nanowire growth. The morphology showed no significant differences between the nanowires. The emissions from ensembles of nanowires have the same peak position, irrespective of seed particle type. Without the in situ annealing step prior to the nanowire growth, there are significant differences in the emission intensity and emission patterns from nanowires grown from different seed particles. When an in situ annealing step is included, all the resulting nanowires show identical optical emission intensity and emission patterns. This shows the importance of using an in situ annealing step prior to growth. This study demonstrates that different preparation methods for gold seed particles can be used to produce GaAs nanowires with highly similar optical properties. The choice of particle preparation method to be used can therefore be based on availability and cost.


Toward understanding the connections between infant jaundice and infant feeding.
Parents face a paradox when they are told: Breast is best; bottle-feeding is hazardous to health. But breast-fed babies are more likely to become severely jaundiced than bottle-fed babies, and severe jaundice can lead to brain damage. This article will explore the natural physiology of jaundice with a focus on breast-feeding-associated jaundice, primary prevention of hyperbilirubinemia, and current evidence-based recommendations about feeding jaundice breast-fed infants.


The NIH 3D Print Exchange: A Public Resource for Bioscientific and Biomedical 3D Prints.
The National Institutes of Health (NIH) has launched the NIH 3D Print Exchange, an online portal for discovering and creating bioscientifically relevant 3D models suitable for 3D printing, to provide both researchers and educators with a trusted source to discover accurate and informative models. There are a number of online resources for 3D prints, but there is a paucity of scientific models, and the expertise required to generate and validate such models remains a barrier. The NIH 3D Print Exchange fills this gap by providing novel, web-based tools that empower users with the ability to create ready-to-print 3D files from molecular structure data, microscopy image stacks, and computed tomography scan data. The NIH 3D Print Exchange facilitates open data sharing in a community-driven environment, and also includes various interactive features, as well as information and tutorials on 3D modeling software. As the first government-sponsored website dedicated to 3D printing, the NIH 3D Print Exchange is an important step forward to bringing 3D printing to the mainstream for scientific research and education.


Use of Prophylactic Antibiotics to Prevent Urinary Tract Infection after Urodynamic Testing and Cystoscopy in Women: A Practice Pattern Study.
The objective of the study was to determine practice patterns of prescribing prophylactic antibiotics against urinary tract infection (UTI) for urodynamic studies (UDS) and outpatient cystoscopy in women. A cross-sectional survey study was conducted of North American female pelvic medicine and reconstructive specialists (FPMRS). An online survey was used to assess prophylactic prescribing patterns of FPMRS that perform UDS and outpatient cystoscopy. This survey was developed and then electronically disseminated through the American Urogynecologic Society to 699 eligible physicians. A total of 138 surveys were completed. Approximately half of physicians did not prescribe any antibiotic prophylaxis for UDS or for cystoscopy (54% and 43%, respectively). For patients with perceived risk factors (recurrent UTIs, immunosuppression, known neurogenic lower urinary tract dysfunction, indwelling catheter use, elevated postvoid residual/bladder outlet obstruction, genitourinary anomalies, and diabetes), 32% and 41% of physicians prescribed antibiotic prophylaxis for UDS and cystoscopy, respectively. A minority of physicians always prescribed antibiotics for UDS and cystoscopy (13% and 17%, respectively). The response rate was a limitation of the study; however, this rate is in keeping with other physician survey studies published within this subspecialty. Selection and response biases may have contributed to the results of this survey study. There was no uniform approach to UTI prophylaxis for UDS and outpatient cystoscopy in women which reflects the lack of current guidelines and the low level of evidence on which they are based. This nonuniform practice calls for more research to better define an evidence-based standard of care.


4,6-Dichloro-5-(2-meth-oxy-phen-oxy)-2,2'-bipyrimidine.
In the title compound, C(15)H(10)Cl(2)N(4)O(2), the dichloro-pyrimidine and meth-oxy-phen-oxy parts are approximately perpendicular [dihedral angle = 89.9 (9)°]. The dihedral angle between the two pyrimidine rings is 36.3 (4)° In the crystal, there are no hydrogen bonds but the mol-ecules are held together by short inter-molecular C⋯N [3.206 (3) Å] contacts and C-H⋯π inter-actions.


[Leishmaniasis a neglected but serious tropical disease].
Visceral leishmaniasis is an uncommon, imported infectious disease in Sweden. Only two cases have been reported 1996-2016. During the last year, however, three cases of visceral leishmaniasis in children less than 3 years old have been treated at the Astrid Lindgren Children's Hospital in Stockholm. They have all been infected during vacation in Southern Europe within their first year of life. We want to raise the awareness regarding this serious neglected tropical disease in the Swedish health care by describing these three cases.


[Regulation of body weight and food palatability].
It is as though the body weight, or a variable correlated closely with body weight, was submitted to regulation. This regulation is analyzed from known human studies. This short bibliography study reviews interrelations between palatability of food stuffs and ponderostat. Findings show that palatability elevates ingestion rate, metabolic output rate and ponderostat set point. Reciprocally, ingestion and the set point modulate food palatability.


Induction of IL-25 Expression in Human Nasal Polyp Epithelium by Influenza Virus Infection is Abated by Interferon-Alpha Pretreatment.
Epithelial cytokines including IL-25, IL-33 and thymic stromal lymphopoietin (TLSP) are recently established as drivers of type 2 chronic inflammatory diseases such as chronic rhinosinusitis with nasal polyps (CRSwNP). Here, we further confirmed the increased expression of IL-25 in CRSwNP and investigated potential contributors of IL-25 in CRSwNP epithelium. Sixty CRSwNP, 25 CRSsNP and 15 healthy control tissues were examined for IL-25 expression and for the accompanying type 2 inflammatory cytokines. We then tested different respiratory virus infections on human nasal epithelial cells (hNECs) for their ability to trigger IL-25 expression. In addition, we subjected hNECs generated from CRSwNP tissues to pretreatment with recombinant interferon-alpha (IFN-α) prior to viral infection to evaluate IFN effects on IL-25 induction. We confirmed that significantly enhanced levels of IL-25 were observed in CRSwNP tissues, and that IL-25 expression correlated with type 2 inflammatory cytokine expression. In vitro, we observed significantly elevated IL-25 in hNECs infected with influenza A virus as early as 24 hours post-infection (hpi), regardless of tissue origin, and IL-25 correlated positively with viral load. While other respiratory viruses exhibited increasing trends of IL-25, these were not significant at the time-points tested. IFN-α treatment of CRSwNP epithelium was found to exert bimodal effects, ie IFN-α treatment alone induced moderate IL-25 expression, whereas IFN-α pretreatment of hNECs before influenza infection significantly diminished IL-25 induction by active influenza virus infection. We have authenticated the observation of elevated IL-25 in CRSwNP, which is correlated with type 2 inflammatory cytokines. Notably, we identified influenza virus infection as a potential contributor of IL-25 in both control and CRSwNP epithelium during active infection. This IL-25 induction can be abated by IFN-α pretreatment which ameliorated active influenza infection. Chictr.org.cn ChiCTR-BON-16010179, Registered 18 December 2016, http://www.chictr.org.cn/showproj.aspx?proj=17331. The authors agree on the sharing of deidentified participant data where it pertains to request directly related to the data in this article when contacted (Haiyu Hong; firstname.lastname@example.com).


Hyaluronic acid-dependent pericellular matrices in fetal fibroblasts: implication for scar-free wound repair.
Fetal fibroblasts are intrinsically different from postnatal fibroblasts. We studied the differences in expression, size, and assembly of pericellular matrices in human fetal and postnatal fibroblasts, as well as the effect of fetal fibroblast-conditioned media as a source of migration stimulating factor on pericellular matrix formation. Fibroblasts in their fifth to fifteenth passages were cultured for 24 hours before analysis. Streptomyces hyaluronidase (0.1 U/ml), monoclonal mouse anti-human CD-44std, or anti-human CD-4 antibodies were added and incubated for 1 hour (at 4 degrees and 37 degrees C) before analysis of the pericellular matrices with the use of a particle exclusion technique. The pericellular matrix/cell body ratio of fetal fibroblasts was significantly larger than that of newborn (p < 0.002) and adult (p < 0.001) fibroblasts. Hyaluronidase disrupted the pericellular matrices in all three cell lines. Assembly of the pericellular matrices was blocked by anti-human CD-44std antibody but not by anti-human CD-4 antibody at both 4 degrees and 37 degrees C. Incubation of fibroblast cell lines in fetal fibroblast-conditioned media did not increase pericellular matrix/cell body ratio but did increase the percentage of fibroblasts expressing a detectable pericellular matrix in adult (p < 0.01), newborn (p < 0.001), and fetal (p < 0.005) fibroblasts. We conclude that fibroblasts produce hyaluronic acid-dependent pericellular matrices which require interaction with a hyaluronic acid-binding protein for assembly. Large pericellular matrices are one intrinsic factor characterizing a unique fetal fibroblast phenotype.


catena-Poly[[[4-bromo-2-(2-pyridylmethyliminomethyl)phenolato]zinc(II)]-mu-chloro].
The title complex, [Zn(C13H10BrN2O)Cl]n, is a chloride-bridged polynuclear zinc(II) compound. Each ZnII ion is five-coordinated in a square-pyramidal configuration, with one O and two N atoms of one Schiff base and one bridging Cl atom defining the basal plane, and another bridging Cl atom occupying the apical position. The novelty of the compound lies in the bridging by chlorine of two square-pyramidal Zn atoms, so that the bridging atom is apical for one Zn ion and basal for the other. This structural arrangement has not been observed before. The linked moieties form polymeric zigzag chains running along the a axis.


A phenazine-imidazole based ratiometric fluorescent probe for Cd2+ ions and its application in in vivo imaging.
A new phenazine-imidazole based Schiff base (PIS) fluorescent probe has been developed for the ratiometric detection of Cd2+ ions in aqueous media at physiological pH. PIS upon binding with Cd2+ ions shows red shifted fluorescence and thereby, permits ratiometric detection of Cd(II) ions. A detection limit down to 2.10 × 10-8 M was determined for Cd2+ quantitation. Also, the accompanying apparent fluorescence color change (from yellow to orange red) is noticeable to the naked eye under a UV-lamp. The sensing mechanism could be attributed to the 1 : 1 PIS-Cd complexation, followed by extension of the conjugation due to better planarity and modulation of the charge transfer efficiency in the probe. This was complemented by solvatochromism and density functional theory calculations. Furthermore, PIS was used to detect Cd2+ in Oxya chinensis cells, zebrafish larvae and live tissues of Arabidopsis thaliana under a fluorescence microscope, showing great potential in analyzing living biosystems.


Responsiveness of pituitary hGH to GRH1-44 in juveniles with obesity.
The response of plasma hGH to an iv bolus injection of GRH1-44 (1 microgram/kg) was studied in 14 obese juveniles with a mean overweight of 4.7 +/- 0.05 standard deviation score (SDS). Two patterns of response were observed: in all 7 adolescents with 'simple' obesity not related to any particular disorder (group A) the response was good (a mean of 11.8 +/- 2.4 ng/ml) whereas in 6 of the 7 juveniles suffering from syndromes associated with obesity (group B) the response was poor (a mean of 3.2 +/- 1.4 ng/ml). This divergence in response could not be related to a difference in the degree of overweight. These results indicate that in group B with syndromes associated with obesity there may also be a pituitary impairment in addition to the hypothalamic defect.


Progranulin Gene Therapy Improves Lysosomal Dysfunction and Microglial Pathology Associated with Frontotemporal Dementia and Neuronal Ceroid Lipofuscinosis.
Loss-of-function mutations in progranulin, a lysosomal glycoprotein, cause neurodegenerative disease. Progranulin haploinsufficiency causes frontotemporal dementia (FTD) and complete progranulin deficiency causes CLN11 neuronal ceroid lipofuscinosis (NCL). Progranulin replacement is a rational therapeutic strategy for these disorders, but there are critical unresolved mechanistic questions about a progranulin gene therapy approach, including its potential to reverse existing pathology. Here, we address these issues using an AAV vector (AAV-Grn) to deliver progranulin in Grn-/- mice (both male and female), which model aspects of NCL and FTD pathology, developing lysosomal dysfunction, lipofuscinosis, and microgliosis. We first tested whether AAV-Grn could improve preexisting pathology. Even with treatment after onset of pathology, AAV-Grn reduced lipofuscinosis in several brain regions of Grn-/- mice. AAV-Grn also reduced microgliosis in brain regions distant from the injection site. AAV-expressed progranulin was only detected in neurons, not in microglia, indicating that the microglial activation in progranulin deficiency can be improved by targeting neurons and thus may be driven at least in part by neuronal dysfunction. Even areas with sparse transduction and almost undetectable progranulin showed improvement, indicating that low-level replacement may be sufficiently effective. The beneficial effects of AAV-Grn did not require progranulin binding to sortilin. Finally, we tested whether AAV-Grn improved lysosomal function. AAV-derived progranulin was delivered to the lysosome, ameliorated the accumulation of LAMP-1 in Grn-/- mice, and corrected abnormal cathepsin D activity. These data shed light on progranulin biology and support progranulin-boosting therapies for NCL and FTD due to GRN mutations.SIGNIFICANCE STATEMENT Heterozygous loss-of-function progranulin (GRN) mutations cause frontotemporal dementia (FTD) and homozygous mutations cause neuronal ceroid lipofuscinosis (NCL). Here, we address several mechanistic questions about the potential of progranulin gene therapy for these disorders. GRN mutation carriers with NCL or FTD exhibit lipofuscinosis and Grn-/- mouse models develop a similar pathology. AAV-mediated progranulin delivery reduced lipofuscinosis in Grn-/- mice even after the onset of pathology. AAV delivered progranulin only to neurons, not microglia, but improved microgliosis in several brain regions, indicating cross talk between neuronal and microglial pathology. Its beneficial effects were sortilin independent. AAV-derived progranulin was delivered to lysosomes and corrected lysosomal abnormalities. These data provide in vivo support for the efficacy of progranulin-boosting therapies for FTD and NCL.


Insight into infection-mediated prostate damage: Contrasting patterns of C-reactive protein and prostate-specific antigen levels during infection.
To investigate mechanisms underlying our previous observation of a large rise in serum prostate-specific antigen, a marker of prostate pathology, during both sexually transmitted and systemic infections, we measured serum high-sensitivity C-reactive protein (hsCRP), a marker of systemic inflammation, in our previous case-control study of young, male US military members and compared our findings to those for PSA. We measured hsCRP before and during infection for 299 chlamydia, 112 gonorrhea, and 59 non-chlamydial, non-gonococcal urethritis (NCNGU) cases; before and after infection for 55 infectious mononucleosis (IM) and 90 other systemic/non-genitourinary cases; and for 220-256 controls. Only gonorrhea cases were significantly more likely to have a large hsCRP rise (≥1.40 mg/L or ≥239%) during infection than controls (P < 0.01). However, gonorrhea, IM, and other systemic/non-genitourinary cases were more likely to have a rise of any magnitude up to one year post-diagnosis than controls (p = 0.038-0.077). These findings, which differ from those for PSA, suggest distinct mechanisms of elevation for hsCRP and PSA, and support both direct (eg, prostate infection) and indirect (eg, systemic inflammation-mediated prostate cell damage) mechanisms for PSA elevation. Future studies should explore our PSA findings further for their relevance to both prostate cancer screening and risk.


Serum creatine kinase is an unreliable predictor of ectopic pregnancy.
To compare serum creatine kinase (CK) values in patients with ectopic pregnancy vs patients with threatened miscarriage or normal pregnancy. An observational case-control study was performed at an urban teaching hospital. Pregnant women with a quantitative beta-hCG obtained for suspicion of ectopic pregnancy were evaluated. Excluded were cases with recent trauma, i.m. injections, surgery, or history of heart, liver, or muscle disease. The serum beta-hCG and CK values were recorded and compared between groups with 1-way ANOVA and Tukey's multiple comparison procedure at the overall 0.05 level. The 15 ectopic, 28 threatened miscarriage, and 21 normal pregnancy cases were of similar gestational ages (p = 0.2), ranging from 3 to 12 weeks. Although the CK values for ectopic pregnancy (88.8 +/- 33.6 IU/L) exceeded those for threatened miscarriage (65.9 +/- 59.0 IU/L) and normal pregnancy (56.0 +/- 38.1 U/L) (p = 0.02), there was significant overlap between groups. CK values were at or above a cutoff of 74 IU/L in 80% (95% confidence interval: 52-96%) of ectopic pregnancies, 25% (11-45%) of threatened miscarriages, and 14% (3-36%) of normal pregnancies. Although the ectopic pregnancy population is characterized by a higher mean CK than are patients with threatened miscarriage or a normal pregnancy, a significant overlap in CK values makes use of this serum marker unreliable for detecting ectopic pregnancy.


Novel therapeutic approaches based on the pathological role of gut dysbiosis on the link between nonalcoholic fatty liver disease and insulin resistance.
The growing global epidemic of obesity and type 2 diabetes mellitus has determined an increased prevalence of NAFLD (non-alcoholic fatty liver disease), making it the most common chronic liver disease in the Western world and a leading cause of liver transplantation. In the last few years, a rising number of studies conducted both on animal and human models have shown the existence of a close association between insulin resistance (IR), dysbiosis, and steatosis. However, all the mechanisms that lead to impaired permeability, inflammation, and fibrosis have not been fully clarified. Recently, new possible treatment modalities have received much attention. To reach the review purpose, a broad-ranging literature search on multidisciplinary research databases was performed using the following terms alone or in combination: "NAFLD", "gut dysbiosis", "insulin resistance", "inflammation", "probiotics", "Chinese herbs". The use of probiotics, prebiotics, symbiotics, postbiotics, fecal microbiota transplant (FMT), Chinese herbal medicine, antibiotics, diet (polyphenols and fasting diets), and minor therapies such as carbon nanoparticles, the MCJ protein, water rich in molecular hydrogen, seems to be able to improve the phenotypic pattern in NAFLD patients. In this review, we provide an overview of how IR and dysbiosis contribute to the development and progression of NAFLD, as well as the therapeutic strategies currently in use.


Glucose-6-phosphate dehydrogenase in lichen planus skin.
The apparent Michaelis constant (Km) for glucose-6-phosphate of the enzyme glucose-6-phosphate dehydrogenase has been measured in extracts prepared from biopsies of normal human skin and from both affected and apparently normal skin of patients with lichen planus. No differences of Km were found and starch gel electrophoresis of extracts from lichen planus lesions and normal controls showed similar patterns when stained for glucose-6-phosphate dehydrogenase activity. These results do not support the view that lichen planus is an inborn error of metabolism in which the structure of glucose-6-phosphate dehydrogenase of skin is affected.


The diabetic intrauterine milieu has a long-lasting effect on insulin secretion by B cells and on insulin uptake by target tissues.
From our previous work, it appears that fetal development in the abnormal intrauterine milieu of a mother with diabetes results in impaired glucose tolerance in adult life. In adult Wistar rats that were the offspring of mildly or severely diabetic mothers, in vitro islet stimulation and in vivo insulin uptake studies were undertaken to distinguish between alterations in glucose sensitivity and insulin secretion at the B cell level and alterations in insulin sensitivity and uptake at the level of the peripheral tissues. Insulin output after glucose stimulation by isolated islets was lower than normal in the rats of mothers with mild diabetes and higher than normal in the animals of severely diabetic mothers, confirming the results of previous in vivo studies. Insulin binding by the liver was normal in both groups. Insulin uptake by the kidney was normal in rats with mildly diabetic mothers but was increased in rats of severely diabetic mothers, suggesting decreased uptake of insulin by the peripheral tissues. Impaired glucose tolerance in rats of mildly diabetic mothers, resulting from decreased responsiveness to glucose, is interpreted as a consequence of hyperactivity of these B cells during the intrauterine life. Impaired glucose tolerance in rats of severely diabetic mothers, associated with insulin hypersecretion and decreased insulin uptake by the peripheral tissues might result from intrauterine alterations of the peripheral receptor or postreceptor system induced by the abnormal intrauterine milieu. These data on experimental diabetes in the rat demonstrate that the maternal diabetic environment exerts a diabetogenic influence on the offspring.


Nuclear receptor-dependent transcription with chromatin. Is it all about enzymes?
Nuclear receptors (NRs) are ligand-regulated, DNA-binding transcription factors that function in the chromatin environment of the nucleus to alter the expression of subsets of hormone-responsive genes. It is clear that chromatin, rather than being a passive player, has a profound effect on both transcriptional repression and activation mediated by NRs. NRs act in conjunction with at least three general classes of cofactors to regulate transcription in the context of chromatin: (a) chromatin remodelers; (b) corepressors; and (c) coactivators, many of which have distinct enzymatic activities that remodel nucleosomes or covalently modify histones (e.g. acetylases, deacetylases, methyltransferases, and kinases). In this paper, we will present a brief overview of these enzymes, their activities, and how they assist NRs in the repression or activation of transcription in the context of chromatin.


VOC emission characteristics of petrochemical wastewater treatment facilities in southern Taiwan.
The wastewater treatment plants (WWTPs) of three representative petrochemical plants in southern Taiwan were sampled to investigate their VOC emission characteristics. Generally, emissions decline along the process flow, while the VOC concentration accumulates to as much as around 2400mg/m3 (as total hydrocarbons) at several closed vessel vents during the primary treatment. VOC emission rates (g/s) and fluxes (g/m2 hr) exhibit a similar trend of reducing concentrations in the WWTPs. From the field analysis data. VOC emission potential is best indicated by the concept of emission flux rather than concentration or emission rate. The Water 8 emission model version 4, developed by the U.S. EPA in 1995, was used to simulate the emission rate. The output results were compared to the calculated VOC liquid-gas mass equilibrium based essentially on the saturated gas concentration (Cg*) of the individual VOC components in wastewater. The comparisons clearly identified the proposed mass transfer approach using (Cg* as a reliable timesaving alternative to Water 8, which requires numerous input parameters and water analysis data.


Trizivir.
Treatment of HIV infection has typically been carried out using two nucleoside analogues and a protease inhibitor (PI). Such regimens can be complex and have high pill burdens. Use of alternative regimens, such as triple nucleoside based regimens, can improve adherence and decrease toxicities associated with PI therapy. Trizivir is a combination tablet of zidovudine, lamivudine and abacavir. This formulation allows a dosing schedule of one pill twice-daily. The components of have performed favourably compared to PI-based regimens, such as indinavir. However, in one study the individual components of Trizivir did not suppress HIV-1 viral replication as well as the PI-based regimen in a subset of patients with very high HIV-1 plasma RNA. Trizivir also avoids side effects of antiretroviral therapy, such as hyperlipidaemia, but its use is associated with a hypersensitivity reaction in a small number of patients. Trizivir is an important part of the HIV armamentarium. The potency and ease of administration of Trizivir make it worth consideration in HIV therapy, either by itself or in combination with other agents.


In vitro cytostatic activity of 8-substituted and tricyclic analogues of acyclovir.
Out of a series of twenty 8-substituted or/and 1,N-2-bridged (tricyclic) derivatives of acyclovir (a selective antiherpetic drug), known to be nontoxic to normal cells, seven compounds were found to exhibit moderate cytostatic activity in KB human tumor tissue culture system with ED50 activity values ranging from 0.052-0.094 x 10(-3) mole/l. The structure-activity relationship analysis indicated that the primary factors determining their cytotoxicity were: 1) bromine atom at the C-8 position of the bicyclic derivatives and 2) unsubstituted appended ring in the tricyclic derivatives. Combination of two structural elements carrying the cytotoxicity gave diverse effects, enhancement or decrease in activity depending on particular cases. Two compounds (of four selected), 8-bromoacyclovir and 1,N-2-etheno-acyclovir, having unsubstituted 9-[(2-hydroxyethoxy)methyl] chain, showed approximately 2-fold increase in their cytotoxicity against HeLa tumor cells in the presence of the induced microsomal generating system suggesting that their cytotoxicity depends on the drug metabolic transformation into their active metabolites (intermediates) via MFO-system, and that structural unit of this chain is essential for abovementioned activation. Presently found remarkable cytotoxic selectivity of acyclovir analogues against KB and HeLa tumor cells together with previously reported in the literature specific cytotoxic activity of acyclovir against murine leukemia L 1210 cells seem to be encouraging for further investigation of this class of compounds in other tumor systems.


Potential role for all-trans retinoic acid in nonpromyelocytic acute myeloid leukemia.
All-trans retinoic acid (ATRA) has been very successful in the subtype of acute myelogenous leukemia known as acute promyelocytic leukemia due to targeted reactivation of retinoic acid signaling. There has been great interest in applying this form of differentiation therapy to other cancers, and numerous clinical trials have been initiated. However, ATRA as monotherapy has thus far shown little benefit in nonacute promyelocytic leukemia acute myelogenous leukemia. Here, we review the literature on the use of ATRA in combination with chemotherapy, epigenetic modifying agents and targeted therapy, highlighting specific patient populations where the addition of ATRA to existing therapies may provide benefit. Furthermore, we discuss the impact of recent whole genome sequencing efforts in leading the design of rational combinatorial approaches.


A novel adjustment method for shearer traction speed through integration of T-S cloud inference network and improved PSO.
In order to efficiently and accurately adjust the shearer traction speed, a novel approach based on Takagi-Sugeno (T-S) cloud inference network (CIN) and improved particle swarm optimization (IPSO) is proposed. The T-S CIN is built through the combination of cloud model and T-S fuzzy neural network. Moreover, the IPSO algorithm employs parameter automation adjustment strategy and velocity resetting to significantly improve the performance of basic PSO algorithm in global search and fine-tuning of the solutions, and the flowchart of proposed approach is designed. Furthermore, some simulation examples are carried out and comparison results indicate that the proposed method is feasible, efficient, and is outperforming others. Finally, an industrial application example of coal mining face is demonstrated to specify the effect of proposed system.


[Guillain-Barré syndrome and pregnancy].
Guillain-Barré syndrome is a rare occurrence in pregnant women. We describe the case of a 21-year old woman, seen at "Nuevo Hospital Civil de Guadalajara" with a term pregnancy, who presented with limbs weakness and paresthesias, drowsiness and malaise. Her vital signs were normal but she was quadriparetic, there was muscular atrophy in the extremities and deep tendon reflexes were decreased. Spinal fluid analysis revealed a protein of 71.2 mg/dl, glucosa 48 mg/dl and no white cells and both Gram stain and routine cultures were negative. EMG studies reported poliradiculoneuritis; a C-section was done, and both the mother and a newborn girl did very well. Guillain-Barré syndrome should be suspected in similar cases in order to offer prompt intervention.


Spatial effects of trade, foreign direct investment (FDI), and natural resource rents on carbon productivity in the GCC region.
Natural resource rents (NRRs) may determine the environment and economic growth of the GCC countries due to their over-reliance on the natural resource sector. NRRs are the source of income in resource-abundant GCC countries. So, increasing income of these countries could pollute the environment by increasing overall economic activities. Consequently, NRRs could determine carbon productivity in the GCC region through increasing income and carbon emissions. The effects of trade openness (TO), foreign direct investment (FDI), urbanization, and oil and natural gas rents on carbon productivity (CP) are examined in the GCC region from 1980-2021 using the spatial Durbin model. The CP of the GCC countries has spillovers in their neighboring countries. Oil rent reduces carbon productivity in domestic economies and the entire GCC region. Natural gas rent, TO, and FDI increase, and urbanization reduces carbon productivity in neighboring economies and the entire GCC region. Moreover, urbanization reduces carbon productivity in domestic economies as well. The study recommends the GCC countries to reduce reliance on oil rent and increase globalization in terms of TO and FDI in the region to promote carbon productivity. Moreover, GCC countries should also focus more on natural gas rent instead of oil rent to raise carbon productivity.


Train related injuries: A descriptive analysis highlighting orthopaedic injuries and management.
Orthopaedic injuries constitute a major aspect of morbidity and mortality following train accidents. The pattern of orthopaedic/musculoskeletal injuries sustained following these accidents has not been fully characterised. The main aim of this study is to describe the range of orthopaedic injuries reported in a major trauma centre and evaluate their management, as well as reporting mortality and amputation rates. Further aims are to identify the social and demographic background of the patients to suggest treatment and prevention strategies. This study is a retrospective observation of all clinical files of patients presented to Level 1 Trauma Centre in Cape Town, South Africa, as "train casualty" from January 2013 to July 2019, which were reviewed and evaluated. A total of 174 patients were included, of which 92 were orthopaedic referrals. The average age was 29 years, and 87% were male. Tibial fractures were most common (N = 19), 38% of patients sustained open fractures, and 68% of patients (in total) underwent surgery. Wound debridement was the most common operation, followed by open reduction internal fixation (ORIF). Twelve patients (13%) underwent amputation to 14 body parts. Eight patients (4.6%) (in total) died in the trauma unit. This study provides insight into train accident victims and their orthopaedic injuries and management patterns. The victims are largely young males. The majority of orthopaedic injuries require surgical intervention, and those who make it to the hospital have a good chance of survival and limb salvage. It appears that in addition to early hospital access and specialised updated treatments, morbidity and mortality in train accidents could be reduced by improving safety measures and social awareness to reduce railway violence and accidents.


Dosimetric Effect of Intrafraction Tumor Motion in Lung Stereotactic Body Radiotherapy Using CyberKnife Static Tracking System.
We investigated the dosimetric effect of intrafraction tumor motion in lung stereotactic body radiotherapy using the CyberKnife static tracking system. Four-dimensional computed tomography scans of a dynamic thorax phantom were acquired. Two motion ranges, 3 collimator sizes, and 4 treatment starting phases were investigated. Monte Carlo dose distributions were calculated on internal target volume with a treatment-specific setup margin for 6 Gy/1 fraction. Dosimetric effects of intrafractional tumor motion were assessed with Gafchromic films. γ (5%/3 mm), dose differences, and distance to agreement were analyzed. With 30 mm collimator plans, the measured dose passed the criteria γ (5%/3 mm) in all tumor motion ranges. The γ passing rates of the plans using 20 mm or 20+35 mm collimators were much lower than that with 30 mm collimator, especially with the 30 mm tumor motion range. The measured dose of 10 mm tumor motion ranges all passed the 90% criteria of γ (5%/3 mm), the results being much better than those of 30 mm tumor motion ranges, which were below 80%. The results of same delivered plan but treated with different starting phases varies greatly. Xsight Lung Tracking technique should be used with caution in lung cancer stereotactic body radiation therapy because the temporal dose variations can be significant.


Carcinoma of the male breast: a review of 41 cases.
We reviewed the cases of 41 consecutive men treated for breast carcinoma from 1950 through 1987 at Vanderbilt University Affiliated Hospitals to examine controversies in and methods of therapy for this disease. Twenty-two patients (52%) had stage I or II lesions potentially curable by operative therapy. The overall 5-year survival rates were 100% for stage I, 65% for stage II, 56% for stage III, and 0% for stage IV. Radical mastectomy offered no advantage over modified radical mastectomy in terms of survival or rate of recurrence. Diagnosis at an early clinical stage and no finding of disease in axillary lymph nodes were important factors in survival in this series of patients. All tumors evaluated for hormone receptors were positive. Although experience was limited, encouraging results were obtained with the use of tamoxifen citrate in adjuvant as well as palliative roles. With the exception of a predominance of centrally located lesions and a uniquely high frequency of positive hormone receptor status, carcinoma of the male breast appears biologically similar to the disease in women, and treatment should be guided by similar principles.


The role of metal nanoparticles in influencing arbuscular mycorrhizal fungi effects on plant growth.
A knowledge gap still remains concerning the in situ influences of nanoparticles on plant systems, partly due to the absence of soil microorganisms. Arbuscular mycorrhizal fungi (AMF) can form a mutualistic symbiosis with the roots of over 90% of land plants. This investigation sought to reveal the responses of mycorrhizal clover (Trifolium repens) to silver nanoparticles (AgNPs) and iron oxide nanoparticles (FeONPs) along a concentration gradient of each. FeONPs at 3.2 mg/kg significantly reduced mycorrhizal clover biomass by 34% by significantly reducing the glomalin content and root nutrient acquisition of AMF. In contrast, no negative effects of AgNPs at concentrations over 0.1 mg/kg were observed; however, AgNPs at 0.01 mg/kg inhibited mycorrhizal clover growth. In response to the elevated AgNPs content, the ability of AMF to alleviate AgNPs stress (via increased growth and ecological behaviors) was enhanced, which decreased Ag content and the activities of antioxidant enzymes in plants. These results were further supported by X-ray microcomputed tomography. Our findings suggest that in soil ecosystem, the influence of nanometals on plant systems would be more complicated than expected, and more attention should be focused on plant responses in combination with those of soil microorganisms.


Telemedicine to integrate intermittent surgical services into primary care.
Assessment of the logistics, economic feasibility, and accuracy of presurgical and postsurgical telemedicine consultations is reported. Virtual patient-surgeon consults were achieved through the use of desktop and laptop computers, digital video, and still cameras using two communications modalities. Patients were selected from rural clinics in the southern Oriente region and from communities located in the Andes Mountain range outside of Cuenca, Ecuador. Patients were evaluated preoperatively and postoperatively by general surgeons working with the Cinterandes Foundation, a not-for-profit organization providing surgical care in remote regions of Ecuador in cooperation with the Ministry of Health's primary care program. Preoperative and postoperative telemedicine consultations had a high measure of clinical accuracy and some economic value. Data were collected from several sites throughout the country during the course of the project. Formidable challenges were encountered and are reported here.


A CT Radiomics-Based Risk Score for Preoperative Estimation of Intraoperative Superior Mesenteric-Portal Vein Involvement in Pancreatic Ductal Adenocarcinoma.
The current radiologic criteria for assessing intraoperative superior mesenteric-portal vein (SMPV) involvement (i.e., presence of tumor-SMPV contact >180° or venous deformity) in pancreatic ductal adenocarcinoma (PDAC) are highly specific but insufficiently sensitive. Therefore, development of improved markers for a more accurate prediction is essential. This study aimed to develop a risk score model to estimate SMPV involvement in PDAC using radiomics analysis of computed tomography (CT) images. Data from two institution-based cohorts of PDAC patients undergoing preoperative CT scans were used to develop (n = 173) and validate (n = 156) a radiomics-based risk score of SMPV involvement using clinical and imaging variables. A radiomics signature was developed based on 2436 radiomic features extracted from the semi-automatic three-dimensional segmentation ofn CT images. The SMPV involvement risk score was built using multivariate logistic regression and compared with the current radiologic criteria. The study surgically identified SMPV involvement in 59 (34.1%) and 57(36.5 %) patients with PDAC in the development and validation cohorts, respectively. A 12-feature-based radiomics signature achieved areas under receiver operating characteristics curves (AUCs) of 0.89 or greater for estimating SMPV involvement. Multivariate regression identified the radiomics signature and SMPV deformity as associated with SMPV involvement. The risk score model had significantly improved AUC (0.928 vs. 0.768; P < 0.001) and sensitivity (84.2% vs. 66.7%; P = 0.025) in the radiologic evaluation. The novel risk score in this study, combining radiomics signature and venous deformity, demonstrated promising performance for estimating SMPV involvement preoperatively for patients with PDAC.


G protein-coupled receptor 101 mRNA expression in the mouse brain: altered expression in the posterior hypothalamus and amygdala by energetic challenges.
GPCR101 is a recently identified orphan G protein-coupled receptor (GPCR) expressed abundantly in the human and mouse hypothalamus. In the absence of a ligand, a direct approach to determine the function(s) of this receptor is not possible. However, clues to the possible functions of GPCR101 may yield from information on the distribution of the receptor and the effect of in vivo manipulation upon the expression level of the receptor. In situ hybridisation on mouse brain sections revealed GPCR101 expression in a number of nuclei, including the amygdala, lateral parabrachial nucleus and nucleus of the solitary tract, as well as in the arcuate nucleus, posterior hypothalamus and paraventricular nucleus of the hypothalamus. Food-deprivation was found to increase GPCR101 mRNA level in the posterior hypothalamus and amygdala. In obese mice bearing the ob gene mutation, GPCR101 mRNA level decreased in the posterior hypothalamus and remained unaltered in the amygdala. By contrast, in both nuclei, GPCR101 mRNA level did not change significantly in obese ob/ob mice after intraperitoneal injection of leptin or in mice fed with a high fat diet. These data suggest that GPCR101 mRNA expression in the posterior hypothalamus and amygdala is regulated by a factor(s) other than leptin. Dual in situ hybridisation was used to establish the relationship between GPCR101 and neuropeptides expressed in the hypothalamus. In the arcuate nucleus, GPCR101 mRNA was expressed in approximately half of the population of neurones expressing the mRNA for the anorexigenic neuropeptide, pro-opiomelanocortin, which suggests a potential functional relationship.


Complement factors and acute phase reactants in the Guillain-Barré syndrome.
The concentrations of C3, C4, C1 inactivator, C3 proactivator and orosomucoid were determined in sera from 13 patients with Guillain-Barré syndrome. The most severely affected patients had the highest levels of C3, C4 and orosomucoid in the acute phase with a slight decline over the following 3-8 weeks. The mildly affected patients had complement concentrations in the upper normal range. In the group of patients with the highest concentrations of C3, C4 and orosomucoid, 4 out of 6 developed residual weakness, while residual weakness was only found in 1 out of 7 with normal concentrations. The measurement of C3 and C4 may, therefore, be of value in estimating the severity and prognosis in the early phase of the disease.


The disposition of coralyne sulphoacetate in rodents.
1. The disposition of (14C) coralyne sulphoacetate has been examined in the mouse and rat at three dose levels. 2. In both species the major route of excretion is biliary following either intraperitoneal or intravenous administration. In rats, 18-24% of the 14C is eliminated in the bile in the first 24 h and only 1-2% in the urine. Transport into bile appears to be active and the transport system saturable at the doses employed. 3. The majority of the biliary 14C in the rats is unchanged parent compound and a minority is associated with a metabolite. The maximum amount of metabolite is 12% at 10-30 min following the administered dose. 4. The initial plasma decay of (14C) coralyne following intravenous administration is rapid. Half-life values are 12-3, 16-2 and 2-41 min after doses of 13, 26 and 52 mg/kg respectively. 5. No sex differences were found in the rat in the parameters studied.


Rhodium-Catalyzed Cycloadditions between 3-Diazoindolin-2-imines and 1,3-Dienes.
Azepino[2,3-b]indoles were regioselectively prepared through rhodium-catalyzed formal aza-[4 + 3] cycloaddition between 3-diazoindolin-2-imines and 1,3-dienes in moderate to good yields. Using 2-[(trimethylsilyl)oxy]-1,3-butadiene as the diene component, azepino[2,3-b]indol-4(1H)-ones were constructed. Furthermore, the reactions of cyclic dienes, such as 1,3-cyclohexadiene and 1,3-cyclopentadiene, furnished the corresponding [3 + 2] cycloaddition products.


Evaluation of Inbred Maize (Zea mays L.) for Tolerance to Low Phosphorus at the Seedling Stage.
In underdeveloped nations where low-input agriculture is practiced, low phosphorus (LP) in the soil reduces the production of maize. In the present study, a total of 550 inbred maize lines were assessed for seedling traits under LP (2.5 × 10-6 mol L-1 of KH2PO4) and NP (2.5 × 10-4 mol L-1 of KH2PO4) hydroponic conditions. The purpose of this study was to quantify the amount of variation present in the measured traits, estimate the genetic involvement of these characteristics, examine the phenotypic correlation coefficients between traits, and to integrate this information to prepare a multi-trait selection index for LP tolerance in maize. A great deal of variability in the maize genotype panel was confirmed by descriptive statistics and analysis of variance (ANOVA). Estimated broad-sense heritability (h2) ranged from 0.7 to 0.91, indicating intermediate to high heritability values for the measured traits. A substantial connection between MSL and other root traits suggested that the direct selection of MSL (maximum shoot length) could be beneficial for the enhancement of other traits. The principal component analysis (PCA) of the first two main component axes explained approximately 81.27% of the variation between lines for the eight maize seedling variables. TDM (total dry matter), SDW (shoot dry weight), RDW (root dry weight), SFW (shoot fresh weight), RFW (root fresh weight), MRL (maximum root length), and MSL measurements accounted for the majority of the first principal component (59.35%). The multi-trait indices were calculated based on PCA using all the measured traits, and 30 genotypes were selected. These selected lines might be considered as the potential source for the improvement of LP tolerance in maize.


Segregation of nucleosomes in replicated mouse alpha-globin gene.
DNA of mouse erythroleukemia cells grown in vitro was labeled with bromodeoxyuridine during cycloheximide-inhibited protein synthesis. Isolated nuclei were digested with micrococcal nuclease to obtain monosomes and monosomal dsDNA. The protection of the heavy and of the light strands of the newly replicated DNA was studied by dot hybridization with the coding and with its complementary noncoding strand of the alpha-globin gene. The results show that both sides of the replication fork contain protected sequences of the gene, thus supporting a bilateral (dispersive) mode of nucleosome segregation during DNA replication.


Can a brief period of double J stenting improve the outcome of extracorporeal shock wave lithotripsy for renal calculi sized 1 to 2 cm?
Extracorporeal shock wave lithotripsy (ESWL) is an established modality for renal calculi. Its role for large stones is being questioned. A novel model of temporary double J (DJ) stenting followed by ESWL was devised and outcomes were assessed. The study included 95 patients with renal calculi sized 1 to 2 cm. Patients were randomized into 3 groups. Group 1 received ESWL only, whereas group 2 underwent stenting followed by ESWL. In group 3, a distinct model was applied in which the stent was kept for 1 week and then removed, followed by ESWL. Procedural details, analgesic requirements, and outcome were analyzed. Eighty-eight patients (male, 47; female, 41) were available for analysis. The patients' mean age was 37.9±10.9 years. Stone profile was similar among groups. Group 3 received fewer shocks (mean, 3,155) than did group 1 (mean, 3,859; p=0.05) or group 2 (mean, 3,872; p=0.04). The fragmentation rate was similar in group 3 (96.7%) and groups 1 (81.5%, p=0.12) and 2 (87.1%, p=0.16). Overall clearance in group 3 was significantly improved (83.3%) compared with that in groups 1 (63.0%, p=0.02) and 2 (64.5%, p=0.02) and was maintained even in lower pole stones. The percentage successful outcome in groups 1, 2, and 3 was 66.7%, 64.5%, and 83.3%, respectively (p=0.21). The analgesic requirement in group 2 was higher than in the other groups (p=0.00). Group 2 patients also had more grade IIIa (2/3) and IIIB (1/2) complications. Stenting adversely affects stone clearance and also makes the later course uncomfortable. Our model of brief stenting followed by ESWL provided better clearance, comfort, and a modest improvement in outcome with fewer sittings and steinstrasse in selected patients with large renal calculi.


Dose- and time-dependent radiation inhibition of RNA and glycosaminoglycan synthesis in embryonic cartilage: an in vitro study.
Radiation effects on the RNA and glycosaminoglycan (GAG) synthesis of embryonic cartilaginous tibiae were studied in vitro during a 4- or 7-day culture period. Before being cultured, tibiae received single radiation doses of 20, 50 or 100 Gy. The counterparts served as sham-irradiated controls. At different times after irradiation, irradiated and control tibiae were pulse-labelled for 2 h with [3H]uridine or [3H]glucosamine. The incorporated radioactivity was measured by liquid scintillation counting. Histochemical demonstration of acid phosphatase (AP), a lysosomal enzyme, was carried out using beta-glycerophosphate as substrate. A limited, dose-dependent immediate effect on RNA and GAG synthesis was found. This effect was unchanged for 2 days. After this period a time-dependent delayed effect was observed. For each radiation dose, and for each precursor, the same time-related pattern was found. At the end of the culture period AP activity, an early indicator for apoptosis, was higher in the irradiated tibiae than in the controls. No other morphological ultrastructural differences were observed at this time. We conclude that the metabolic alterations are probably due to stimulation of the initial stages of the apoptotic process in the irradiated cartilage cells.


Attributes of quality in audiovisual materials for health professionals.
Utilizing a series of meetings and incorporating individual efforts of producers, evaluators, and users of audiovisual materials; an attempt has been made to define the quality of an instructional item. Attributes of quality in content, instructional design, technical production, and packaging of audiovisual materials are addressed through questions about general criteria that permit expression of individual dictates off creativity and taste. These attributes of quality are intended for use by the producers and evaluators of audiovisual instruction.


The carboxy-terminal domain of Sendai virus nucleocapsid protein is involved in complex formation between phosphoprotein and nucleocapsid-like particles.
The replicative unit of Sendai virus, the nucleocapsid, is composed of the viral genomic RNA and the viral proteins NP, P, and L. P and L proteins form a polymerase complex and are associated with the nucleocapsid core (NP/RNA complex). The NP protein has recently been shown to be composed of two domains. While the amino-terminal domain I encapsidates RNA and gives rise to the characteristic helical nucleocapsid structure, the precise function of the carboxy-terminal domain II remained unclear. It was however supposed to be involved in binding the polymerase complex. To test this hypothesis, we established a cosedimentation assay which detects complex formation between P protein and nucleocapsid-like (NC-like) particles. Four mutant NC-like particles all carrying amino acid deletions in domain II of the NP protein were tested. Complex formation was abolished after deletion of amino acids 426-497 or 456-524, while deletions of amino acids 400-415 or 414-439 had no influence on the interaction. The results indicate that domain II of NP protein is involved in binding P protein to nucleocapsids. The function and position of a putative P protein binding site in domain II are discussed.


Herpes simplex keratitis -- an unusual clinical presentation.
A case of posterior corneal abscess with extension into the anterior chamber, in the presence of an intact corneal epithelium and clear anterior corneal stroma, occurring in a young patient is described. The patient responded to treatment with systemic and topical acyclovir. The diagnosis of presumed herpes simplex keratitis was made. We report this unusual presentation of ocular herpes manifesting as a posterior corneal and anterior chamber abscess.


MECC determination of oleanolic acid and ursolic acid isomers in Ligustrum lucidum Ait.
In this paper, a novel method to separate and determine oleanolic acid and ursolic acid isomers in Ligustrum lucidum Ait was studied by micellar electrokinetic capillary chromatography (MECC). The baseline separation of the two analytes were obtained on the condition that the buffer contained 15 mmol/l disodium hydrogen phosphate, 15 mmol/l disodium tetreborate, 10 mmol/l SDS and 5% (v/v) alcohol. The contents of the oleanolic acid and ursolic acid were determined in L. lucidum Ait, Folium photiniae and Flos campsis; they were 78.3 (R.S.D. = 2.75%) and 20.7 mg/g (R.S.D. = 2.97%), 27.9 (R.S.D. = 3.67%) and 79.8 mg/g (R.S.D. = 3.44%), 65.5 (R.S.D. = 3.73%) and 60.4 mg/g (R.S.D. = 4.06%) (n = 5), respectively. The recoveries of the analytes in the extract of L. lucidum Ait were 102%, (R.S.D. = 2.85%) for oleanolic acid and 104% (R.S.D. = 3.21%) for ursolic acid (n = 5). With the emphasis on the effects of SDS and alcohol concentrations on the separation of the isomers were investigated.


On the mechanism of action of SJ-172550 in inhibiting the interaction of MDM4 and p53.
SJ-172550 (1) was previously discovered in a biochemical high throughput screen for inhibitors of the interaction of MDMX and p53 and characterized as a reversible inhibitor (J. Biol. Chem. 2010; 285:10786). Further study of the biochemical mode of action of 1 has shown that it acts through a complicated mechanism in which the compound forms a covalent but reversible complex with MDMX and locks MDMX into a conformation that is unable to bind p53. The relative stability of this complex is influenced by many factors including the reducing potential of the media, the presence of aggregates, and other factors that influence the conformational stability of the protein. This complex mechanism of action hinders the further development of compound 1 as a selective MDMX inhibitor.


Sampling for conditional inference on case-control data.
The problem of exact conditional inference for discrete multivariate case-control data has two forms. The first is grouped case-control data, where Monte Carlo computations can be done using the importance sampling method of Booth and Butler (1999, Biometrika86, 321-332), or a proposed alternative sequential importance sampling method. The second form is matched case-control data. For this analysis we propose a new exact sampling method based on the conditional-Poisson distribution for conditional testing with one binary and one integral ordered covariate. This method makes computations on data sets with large numbers of matched sets fast and accurate. We provide detailed derivation of the constraints and conditional distributions for conditional inference on grouped and matched data. The methods are illustrated on several new and old data sets.


Evaluation and Application of a Novel Diffusive Gradients in Thin-Films Technique for In Situ Monitoring of Glucocorticoids in Natural Waters.
The potential environmental risks of glucocorticoids (GCs) have attracted attention in the past few decades. In this study, a novel diffusive gradients in thin-films (DGT) device and analytical technique based on the second generation of polar enhanced phase (PEP-2), PEP-2-DGT, were developed for sampling and quantifying natural and synthetic GCs in aquatic systems. The capacity of PEP-2 gels for accumulating all target compounds was >600 μg per disc, sufficient for long-term passive sampling of selected GCs, even in wastewaters. Systematic tests were carried out to verify the application of DGT in natural waters and wastewaters. The performance of PEP-2-DGT devices was independent (CDGT/Csoln was in the acceptable range of 0.9-1.1) of a wide range of environmental conditions: ionic strength (0.001-0.5 mol L-1), dissolved organic matter (0-20 mg L-1), and pH (3.06-9.02). It was tested for various diffusive layer thicknesses (0.565-2.065 mm) and different deployment times (10-168 h). Diffusion coefficients (D) of selected GCs through an agarose-based diffusive gel were determined for the first time (3.80-4.85 × 10-6 cm-2 s -1 at 25 °C). Linear correlations between D and log Kow were established for three groups of target GCs (R2 = 0.96-0.99). This could enable prediction of D values for other GCs with similar structures in the future, which will help for rapid screening and emergency monitoring. Concentrations and distribution patterns of analytes obtained by PEP-2-DGT devices in five rivers after 7- and 14-day deployments were in accordance with those measured from grab samples, with total GC concentrations ranging from 7 to 27 ng L-1 at all sampling sites, confirming the reliability and robustness of the DGT devices for monitoring GCs in natural waters. The development of the new DGT technique will help improve understanding of the behavior and fate of these compounds in the aquatic environments.


Improved handling of embedding plastics for electron microscopy.
An improved, safer, rapid method for preparing embedding plastics for electron microscopy is described. The method consists of contained storage and dispensing of individual plastic components on an automatic tare balance. The proportions are based on weight measurements and may be calculated from volume or proportion recipes. The usual problems in and resulting from embedding plastic handling have been eliminated.


Repeated stress-induced stimulation of catecholamine response is not followed by altered immune cell redistribution.
Stress response is considered an important factor in the modulation of immune function. Neuroendocrine hormones, including catecholamines, affect the process of immune cell redistribution, important for cell-mediated immunity. This longitudinal investigation was aimed at evaluating the effect of repeated stress-induced elevation of catecholamines on immune cell redistribution and expression of adhesive molecules. We assessed the responses of epinephrine (EPI), norepinephrine (NE), cortisol, changes in lymphocytes subpopulations, and percentages of CD11a+, CD11b+, and CD62L+ lymphocytes to a 20-min treadmill exercise of an intensity equal to 80% of the individual's Vo(2)max. The exercise was performed before and after 6 weeks of endurance training consisting of a 1-h run 4 times a week (ET) and after 5 days of bed rest (HDBR) in 10 healthy males. We did not observe any significant changes in the basal levels of EPI, NE, and cortisol in the plasma, nor in the immune parameters after ET and HDBR. The exercise test led to a significant (P <.001) elevation of EPI and NE levels after both ET and HDBR, a significant elevation (P <.01) of cortisol after HDBR, an increase in the absolute numbers of leukocytes, granulocytes, monocytes, CD3+, CD4+, CD8+, CD16+, CD19+ lymphocytes, percentage of CD11a+ and CD11b+ lymphocytes, and to a decrease of CD62L1 before, after ET, and after HDBR. We found comparable changes in all measured immune parameters after ET and HDBR. In conclusion, repeated stress-induced elevation of EPI and NE was not associated with an alteration in immune cell redistribution found in response to the single bout of exercise.


Clinical Analysis of Algerian Patients with Pompe Disease.
Pompe's disease is a metabolic myopathy caused by a deficiency of acid alpha-glucosidase (GAA), also called acid maltase, an enzyme that degrades lysosomal glycogen. The clinical presentation of Pompe's disease is variable with respect to the age of onset and rate of disease progression. Patients with onset of symptoms in early infancy (infantile-onset Pompe disease (IOPD)) typically exhibit rapidly progressive hypertrophic cardiomyopathy and marked muscle weakness. Most of them die within the first year of life from cardiac and/or respiratory failure. In the majority of cases of Pompe's disease, onset of symptoms occurs after infancy, ranging widely from the first to sixth decade of life (late-onset Pompe's disease or LOPD). Progression of the disease is relentless and patients eventually progress to loss of ambulation and death due to respiratory failure. The objective of this study was to characterize the clinical presentation of 6 patients (3 with EOPD and the other 3 with LOPD) of 5 families from the East of Algeria. All our patients were diagnosed as having Pompe's disease based on biochemical confirmations of GAA deficiency by dried blood spots (DBS) and GAA gene mutations were analyzed in all patients who consented (n = 4). Our results are similar to other ethnic groups.


Age and sex-adjusted incidence and yearly prevalence of multiple sclerosis (MS) in Mazandaran province, Iran: An 11-years study.
The incidence rate of MS is a valuable indicator of the recent changes in the risk of this disease, and it is widely implicated for health planning purposes. This study aims to determine the MS incidence over the past eleven years in Mazandaran province and to compare it with the other parts of Iran and the world. This retrospective study is conducted in Mazandaran province by using registered data in the files of the patients with their consent. The yearly crude incidence rates, age, and sex-specific incidence rates and directly standardized incidence rates of this population are calculated, and the temporal changes in the incidence rates are analyzed. 662 (26%) male patients with the mean (SD) age of 32.6 (9.48) and 1884 (74%) female patients with the mean (SD) age of 31.9 (9.15) are studied. The direct standardized incidence rate of MS was 3.28 in 100.000 in 2008 and reached 4.17 in 100.000 in 2018, and this increase was significant (p<0.05). Also, the yearly prevalence of MS increased from 24.4 to 72.5 in this period. The MS incidence has increased in Mazandaran. The potential role of some genetic or environmental factors needs further investigation.


Needleless closed system does not reduce central venous catheter-related bloodstream infection: a retrospective study.
The needleless closed system (NCS) has been disseminated in several clinical fields to prevent central venous catheter-related bloodstream infection (CVC-RBSI), in place of the conventional Luer cap system (LCS). The purpose of this study is to examine whether NCS is really superior to conventional LCS for prevention of CVC-RBSI. Between May 2002 and December 2008, 1767 patients received CVC in our department. The time interval from insertion to development of CVC-RBSI was compared retrospectively between selected patients who were treated using the conventional LCS (group 1, n = 89, before June 2006) and the NCS (group 2, n = 406, June 2006 and after). Kaplan-Meier analysis revealed no significant difference in the time interval from insertion to development of CVC-RBSI between the two groups. NCS does not reduce CVC-RBSI in adult colorectal cancer patients who undergo CVC insertion.


Beyond needle sharing: meta-analyses of social context risk behaviors of injection drug users attending needle exchange programs.
This study gathered data from U.S. and international needle exchange programs (NEPs). Of particular interest were outcome measures of dependent variables related to behaviors within social contexts of injection drug users (IDUs), an area not well understood. Thirty-one studies, with a total of 86 separate measures of 36 dependent variables were included. Because combining all results into a single meta-analysis would be inappropriate, dependent variables were placed into five categories for five separate meta-analyses: risky contexts, injection frequency, sharing drug paraphernalia, drug preparation, and syringe use. NEP attendance was inversely related to declines in all categorical behaviors except for "risky context." NEP attenders are slightly more likely to be in a risky circumstance when injecting drugs than non-attenders. While injection frequency declined only slightly among NEP attenders, that result may be interpreted as a positive outcome, given the often-stated criticism that providing clean needles encourages increased drug use. NEP use was weakly associated with a decrease in the sharing of drug paraphernalia. Clean needles alone do not appear to be sufficient motivation to motivate major changes in contextual risk behaviors analyzed herein. Research is needed to assess the impact of interpersonal IDU relationships with other stakeholders (clinic employees, van drivers, medical personnel, nutritionists, sexual partners, etc.) on IDU drug-using behaviors at many levels.


Current approach to epithelial ovarian cancer based on the concept of cancer stem cells.
Epithelial ovarian cancer (EOC) is the most common ovarian malignancy. EOCs comprise a diverse group of neoplasms, exhibiting a wide range of morphological characteristics, genetic alterations, and biological behaviors. Currently, there is no effective screening for early detection of EOCs and more than two-thirds of EOC patients are diagnosed with advanced stage disease. The major limiting factors in the treatment of EOC patients are recurrence and chemoresistance. Recent studies suggest that EOCs, like other solid tumors, contain distinct populations of cells that are responsible for tumor initiation, maintenance and growth. These cells, termed cancer stem cells (CSCs), display some of the features of normal stem cells and are thought to evade current chemotherapeutic strategies for the treatment of EOCs. Distinguishing CSC-associated antigen profiles may elucidate novel, more sensitive biomarkers for early detection of EOCs and provide molecular targets for the development of new treatment modalities. This review summarizes the current approaches to EOCs based on the concept of CSCs and evaluates their clinical relevance.


Achieving High Performance Metal-Organic Framework Materials through Pore Engineering.
Achieving high performance functional materials has been a long-term goal for scientists and engineers that can significantly promote science and technology development and thus benefit our society and human beings. As well-known porous materials, metal-organic frameworks (MOFs) are crystalline open frameworks made up of molecular building blocks linked by strong coordination bonds, affording pore space for storing and trapping guest molecules. In terms of porosity, MOFs outperform traditional porous materials including zeolites and activated carbon, showing exceptional porosity with internal surface area up to thousands of square meters per gram of sample and with periodic pore sizes ranging from sub-nanometer to nanometers. Numerous MOFs have been synthesized with potential applications ranging from storing gaseous fuels to separating intractable industrial gas mixtures, sensing physical and chemical stimulus, and transmitting protons for conduction. Compared to traditional porous materials, MOFs are distinguished for their exceptional capability for pore adjustment and interior modification through pore engineering, which have made them a preeminent platform for exploring functional materials with high performance.Rational combinations of rigid building units of different geometry and multibranched organic linkers have provided MOFs with diverse pore structures, ranging from spherical to cylindrical, slit, and tubular ones isolating or interconnecting in different directions, which can be optimized for high-capacity gas storage. Based on the isoreticular principle and building blocks approach in MOF chemistry, the pore adjustment of porous materials can be performed with exquisite precision, making them suitable to address industrially important gas separation. The large pore cavities in MOFs are readily available for encapsulation of different functional guest species, resulting in novel MOF composite materials with various functions.In this Account, we summarize our recent research progress on pore engineering to achieve high-performance MOF materials. We have been able to tune and optimize pore structures, immobilize specific functional sites, and incorporate guest species into target MOF materials for hydrogen storage, methane storage, light-hydrocarbon purification, and proton conduction, especially for various industrially important gas separations including acetylene removal and ethylene and propylene purification. By engineering the porosity and pore chemistry that endows MOFs with multiple functionalities, our research endeavors have brought about the customization of high-performance MOF materials for corresponding application scenarios.


Simultaneous Fat Injection for Nasal Contouring in Orthognathic Patients.
Augmentation rhinoplasty with autologous fat grafting is a useful procedure to meet the demand for facial harmonization in the Asian population. We used this procedure during orthognathic surgery to address inadequate dorsum projection. This prospective study was conducted to determine the fat retention rate in patients undergoing simultaneous autologous fat injection augmentation rhinoplasty and orthognathic surgery. Nineteen patients were treated with simultaneous bimaxillary orthognathic surgery and autologous fat grafting of the nasal dorsum and tip. The paired t test was used to compare the nasal volumes before and at least 6 months after surgery measured by 3-dimensional computer tomography scans. All measurements were performed twice by the same evaluator at least 2 weeks apart for intrarater consistency. Seventeen patients completed the study. The volume means before and after surgery were 22.3 ± 4.6 cm3 and 23.3 ± 4.7 cm3, respectively, with a mean difference of 1.0 ± 0.3 cm3 (P < .001). The mean retention rate was calculated to be 50.5% ± 7.0% (range: 40.5%-64.7%). Intrarater consistency was high with a Cronbach α of .97 (P < .001) and .98 (P < .001), respectively. This prospective study provides objective graft retention measurements for fat injection augmentation rhinoplasty combined with orthognathic surgery. All patients were satisfied with the results and no complications or additional morbidity was noted in the postoperative course. We consider this procedure to be a safe, reliable, and powerful adjunct to improve the aesthetic results of orthognathic surgery.


Near infrared spectroscopy and transcranial Doppler in monohemispheric stroke.
We simultaneously performed near infrared spectroscopy (NIRS) and transcranial Doppler (TCD) to evaluate the effects of hypercapnia as well as of scalp ischemia on the blood flow at two different depth levels within the brain and of the scalp vessels. A decrease in the backscattered light intensity, meaning an increment of blood volume, was detected at the end of hypercapnia in all healthy subjects. This decrement was partly masked by ischemia in the cutaneous vessels. In 2 patients with a monohemispheric lesion in the middle cerebral artery (MCA) territory, an increase in NIRS response was found in the healthy hemisphere, while in the stroke side the CO2-induced changes were negligible. TCD data showed a similar increment of blood flow velocity to the hypercapnia in both hemispheres, with no differences between the affected and normal side in 1 patient, whereas in the second one, no increment was observed on the affected side, probably due to internal carotid artery stenosis. The two methods nicely integrate: TCD mainly tests subcortical changes in the MCA flow, while NIRS is exquisitely sensitive to cortical arterioles and capillary blood flow modifications.


A molecular reappraisal of matrix-producing breast metaplastic carcinoma highlighted by PLAG1 and MYC rearrangements.
Very little is currently known about molecular alteration of matrix-producing carcinoma of the breast. However, the morphological similarity with other neoplasm with a myxo-chondroid component is remarkable. In this pilot study we evaluated the molecular alterations involving PLAG1 and MYC genes in 12 cases of matrix producing carcinoma. We evaluated PLAG1 rearrangements as Break-Apart and Gene Copy Gain, and MYC as amplification and polysomy in 12 cases of matrix producing carcinoma using a FISH method. Among the 12 cases of matrix producing carcinomas we found that the three cases harboring MYC amplification were all negative for PLAG1 break-apart; four cases with MYC polysomy were associated to PLAG1 break-apart and high Gene Copy Number; among four cases wild type for MYC, three showed a PLAG1- break-apart signal and of them two died with disease. One of the deceased patients showed an amplification of MYC with PLAG1- wild-type and the other showed a PLAG1 break-apart (6%) and a MYC wild-type. This is the first report to the best of our knowledge that shows a possible correlation between a matrix producing carcinoma with PLAG1 and MYC involvement in the development and progression of this kind of tumor. We can suppose that MYC amplification behaves in an aggressive way together with PLAG1- break-apart in the cases of matrix producing carcinoma presented here. The gene copy gain is a useful diagnostic tool in the case of difficult diagnosis because an increase was observed in more than 50% of cases.


A Randomized, Controlled Trial of Vitamin D Supplementation on Cardiovascular Risk Factors, Hormones, and Liver Markers in Women with Polycystic Ovary Syndrome.
Polycystic ovary syndrome (PCOS) increases the risk of metabolic syndrome and non-alcoholic-fatty-liver disease (NAFLD). Vitamin D supplementation may exert positive effects on liver biochemistry in patients with NAFLD; however, its effects on PCOS are unknown. This randomized, double-blind, placebo-controlled study explored the effect of vitamin D supplementation on cardiovascular risk factors (high-sensitivity C-reactive protein (hs-CRP), weight, body mass index (BMI), lipid profile, glucose levels, insulin levels, the homeostatic model assessment-insulin resistance (HOMA-IR), hormones (free androgen index (FAI), testosterone, sex hormone binding globulin (SHBG), and liver markers (alanine aminotransferase (ALT), hyaluronic acid (HA), N-terminal pro-peptide of type III procollagen (PIIINP), tissue inhibitor of metallo-proteinases-1 (TIMP-1), and the enhanced liver fibrosis (ELF) score). Forty women with PCOS were recruited and randomized to vitamin D (3200 IU) or placebo daily for 3 months. All outcomes were measured at baseline and 3 months follow-up (FU). Greater increases in vitamin D levels were shown in the supplementation group (vitamin D, baseline: 25.6 ± 11.4 nmol/L, FU: 90.4 ± 19.5 nmol/L vs. placebo, baseline: 30.9 ± 11.1 nmol/L, FU: 47.6 ± 20.5 nmol/L, p < 0.001). Between groups comparisons (% baseline change) revealed significant differences in ALT (p = 0.042) and a weak effect indicating a greater reduction in the HOMA-IR in the vitamin D group (p = 0.051). No further between group differences were seen in other cardiovascular risk factor, liver markers, or hormones. This study supports beneficial effects of vitamin D supplementation on liver markers and modest improvements in insulin sensitivity in vitamin D deficient women with PCOS.


Isolation of an Entamoeba histolytica intracellular alkaline phospholipase A2.
The major hemolytic activity of Entamoeba histolytica is located in a subcellular fraction called P30. Its maximal effect is observed at pH 8.0 and 1 mM Ca2+ and is due to a phospholipase A (PLA). In the present study a membrane-associated phospholipase A2 was purified from P30 to homogeneity. P30 was fractionated with ethyl ether and the insoluble fraction was extracted with 1 M KCl. The KCl-soluble material was diluted ten times with 0.1 M TRIS-HCl (pH 9.5) and passed through a chromatofocusing column with a 9-4 pH gradient. Four peaks with PLA2 activity were obtained. By affinity chromatography, peak II, the one with the highest specific activity, was resolved in three more PLA2 peaks. Peak II.2 had the highest PLA2 specific activity. When analyzed by sodium dodecyl sulfate-polyacrylamide slab-gel electrophoresis under nonreducing conditions, peak II.2 yielded a single band with an apparent molecular mass of 30 kDa. Under reducing conditions the protein dissociated into two 15-kDa monomers. The purified PLA II.2 displayed its activity at the same conditions under which the P30 hemolytic activity was maximal. The isoelectric point of PLA II.2 was 7.0. The purification procedure described above provides sufficient material for determination of the relative importance of the enzyme in the E. histolytica pathogenic mechanisms.


Conformational transitions of polypeptide chain elongation factor Tu. I. Studies with hydrophobic probes.
The conformational difference between polypeptide chain elongation factor Tu (EF-Tu)-GTP and EF-Tu-GDP has been studied using hydrophobic and fluorescent probes. The interaction of EF-Tu-GDP with 1-anilino-8-naphthalenesulfonate (ANS) was measured in terms of the enhancement of the fluorescence intensity at the emission maximum of 475 nm. When EF-Tu-GDP-ANS complex was converted to EF-Tu-GTP-ANS complex by incubation with phosphoenolpyruvate and pyruvate kinase [EC 22.214.171.124], there was a roughly 2-fold increase in fluorescence intensity and a blue shift of the emission maximum from 475 to 467 nm, indicating a conformational transition of the protein. The conformational change was found to be reversible and the spectrum promptly returned to that of EF-Tu-GDP-ANS complex upon addition of excess GDP. A similar change in the spectrum was also observed when aminoacyl-tRNA, but not deacylated tRNA, was added to EF-Tu-GDP-ANS complex. Measurement of the number of binding sites by gel filtration indicated that EF-Tu-GTP and EF-Tu-GDP bind 2.9 and 1.7 molecules of ANS, respectively. These results suggest that in EF-Tu-GTP the conformation was altered and one additional binding site for ANS was created at or near the site interacting with aminoacyl-tRNA. Another reagent, N-(1-anilinonaphthyl-4) maleimide (ANM) was covalently bound to the sulfhydryl group in EF-Tu-GDP which is essential for interaction with aminoacyl-tRNA. The binding could be determined spectrofluorometrically, since the reagent, which is nonfluorescent in aqueous solution, emitted a strong fluorescence upon binding with the sulfhydryl group, indicating a marked hydrophobicity of the local environment. Measurements of the kinetics of the binding revealed that ANM reacted rapidly with the sulfhydryl group in EF-Tu-GTP, while the reaction with that in EF-Tu-GDP proceeded more sluggishly. The difference in the reactivity of the sulfhydryl group essential for aminoacyl-tRNA binding between EF-Tu-GTP and EF-Tu-GDP probably reflects a conformational transition of the protein near the active site. These results, together with those on spin-label studies previously published (Arai, Kawakita, Kaziro, Maeda, & Onishi (1974) J. Biol. Chem. 249, 3311), demonstrate that reversible conformational transition does occur in EF-Tu on changing the ligand from GDP to GTP.


Determinants of prescription opioid misuse among Black Americans: Evidence from the 2019 National Survey on Drug Use and Health.
Opioid misuse, including prescription opioid misuse, remains a significant public health concern impacting various ethnoracial groups in the United States, including non-Hispanic Black Americans. This study provides more recent evidence on prescription opioid misuse among Black Americans. We used data from the 2019 National Survey on Drug Use and Health to examine the prevalence and determinants of prescription opioid misuse among Black American adults aged 18 and older. We compared these findings to non-Hispanic White American adults. The prevalence rate of past-year prescription opioid misuse was very similar among Black (3.4%) and White respondents (3.8%). Adjusted multivariate logistic regression analyses found no significant racial differences in prescription opioid misuse. Religious importance and rurality were negatively associated with misuse only among Black respondents. Depressive episodes, other drug use, age, and risk-taking behaviors were associated with prescription opioid misuse among both Black and White respondents. Black and White Americans remain at risk for prescription opioid-related problems. Religiosity and rurality require further investigation to understand how they may impact misuse among Black Americans.


Fabrication of supported mesoporous TiO2 membranes: matching the assembled and interparticle pores for an improved ultrafiltration performance.
We report the fabrication and ultrafiltration performances of an asymmetric composite membrane with a mesoporous TiO2 skin layer coated on a macroporous alumina support. Mesoporous TiO2 was first prepared and deposited on the substrate through a sol-gel process where a ethylene oxide and propylene oxide triblock polymer (PEO-PPO-PEO, P123) was used to modify the properties of the sols and also to introduce assembled pores in the skin layer. The obtained mesoporous TiO2 membrane was characterized by means of scanning electron microscopy, transmission electron microscopy, X-ray diffraction, and nitrogen adsorption. We found that there were two types of wormlike mesopores present in the TiO2 membrane: interparticle and assembled pores. By carefully controlling the sol properties, we made the two types of pores match each other, which means the size of the interparticle pores is close or smaller than that of the assembled pores. This pore-size matching ensures a narrow pore-size distribution and, consequently, a good retention performance of the obtained TiO2 membrane. The pore size of the TiO2 membrane is ca. 6 nm, as revealed by both nitrogen adsorption and dextran separation experiments, and it has a pure water flux of 7.12 L/(m(2) x h x bar) and a cutoff molecular weight of 19 000 Da, which is very attractive for applications in the enrichment and separation of proteins and polypeptides.


Large-Scale Differential Gene Expression Transcriptomic Analysis Identifies a Metabolic Signature Shared by All Cancer Cells.
Cancer-dependent metabolic rewiring is often manifested by selective expression of enzymes essential for the transformed cells' viability. However, the metabolic variations between normal and transformed cells are not fully characterized, and therefore, a systematic analysis will result in the identification of unknown cellular mechanisms crucial for tumorigenesis. Here, we applied differential gene expression transcriptome analysis to examine the changes in metabolic gene profiles between a wide range of normal tissues and cancer samples. We found that, in contrast to normal tissues which exhibit a tissue-specific expression profile, cancer samples are more homogenous despite their diverse origins. This similarity is due to a "proliferation metabolic signature" (PMS), composed of 158 genes (87 upregulated and 71 downregulated gene sets), where 143 are common to all proliferative cells but 15 are cancer specific. Intriguingly, the PMS gene set is enriched for genes encoding rate-limiting enzymes, and its upregulated set with genes associated with poor patient outcome and essential genes. Among these essential genes is ribulose-5-phosphate-3-epimerase (RPE), which encodes a pentose phosphate pathway enzyme and whose role in cancer is still unclear. Collectively, we identified a set of metabolic genes that can serve as novel cancer biomarkers and potential targets for drug development.