Sexual minority stress and substance use: An investigation of when and under what circumstances minority stress predicts alcohol and cannabis use at the event-level.
Sexual minority women and gender diverse (SMWGD) individuals are at elevated risk for alcohol and cannabis use disorders compared with cisgender, heterosexual women. This has been attributed to the unique stressors that SMWGD experience (i.e., sexual minority stress); however, recent studies have found mixed evidence for a link between sexual minority stress and substance use. The current manuscript introduces and tests a novel theoretical model derived from integrating minority stress theory and the multistage model of drug addiction to explain these mixed findings. We used data from a 30-day ecological momentary assessment (EMA) study of substance use among SMWGD to determine whether event-level associations between enacted stigma (bias from others) and same-/next-day alcohol and cannabis use are dependent on an individual's typical pattern of substance use (e.g., frequency, quantity, motives, and substance use disorder [SUD] symptoms). Findings indicate that enacted stigma predicted an increased likelihood of alcohol and cannabis use among those who used frequently and those who had a probable alcohol or cannabis use disorder and predicted a decreased likelihood of use among those who used less frequently. Enacted stigma also predicted cannabis (but not alcohol) use among those who reported high coping motives for use. Findings provide initial evidence in support of an integrated model of minority stress theory and the multistage model of drug addiction. Findings suggest that alcohol and cannabis use disorder interventions for SMWGD would benefit from addressing sexual minority stress and coping skill-building. (PsycInfo Database Record (c) 2023 APA, all rights reserved).


Rapid breeding and varietal replacement are critical to adaptation of cropping systems in the developing world to climate change.
Plant breeding is a key mechanism for adaptation of cropping systems to climate change. Much discussion of breeding for climate change focuses on genes with large effects on heat and drought tolerance, but phenology and stress tolerance are highly polygenic. Adaptation will therefore mainly result from continually adjusting allele frequencies at many loci through rapid-cycle breeding that delivers a steady stream of incrementally improved cultivars. This will require access to elite germplasm from other regions, shortened breeding cycles, and multi-location testing systems that adequately sample the target population of environments. The objective of breeding and seed systems serving smallholder farmers should be to ensure that they use varieties developed in the last 10 years. Rapid varietal turnover must be supported by active dissemination of new varieties, and active withdrawal of obsolete ones. Commercial seed systems in temperate regions achieve this through competitive seed markets, but in the developing world, most crops are not served by competitive commercial seed systems, and many varieties date from the end of the Green Revolution (the late 1970s, when the second generation of modern rice and wheat varieties had been widely adopted). These obsolete varieties were developed in a climate different than today's, placing farmers at risk. To reduce this risk, a strengthened breeding system is needed, with freer international exchange of elite varieties, short breeding cycles, high selection intensity, wide-scale phenotyping, and accurate selection supported by genomic technology. Governments need to incentivize varietal release and dissemination systems to continuously replace obsolete varieties.


Nonpoint Source Pollution.
The article presents a comprehensive review of research advancing in 2014 on nonpoint source pollution (NPS). The topics presented relate to nonpoint source pollution (NPS) within agricultural and urban areas. NPS pollution from agricultural areas is the main focus in this review. Management of NPS in agricultural, urban and rural areas is presented. Modeling of NPS pollution in different watersheds with various modeling tools is reviewed.


A palladium-catalyzed glycosylation reaction: the de novo synthesis of natural and unnatural glycosides.
A highly stereoselective and sterospecific palladium-catalyzed glycosylation reaction of a variety of alcohols is reported. The reaction selectively converts alpha-2-substituted 6-carboxy-2H-pyran-3(6H)-ones into alpha-2-substituted 6-alkoxy-2H-pyran-3(6H)-ones with complete retention of configuration and similarly converts the pyranones with beta-carboxy groups into pyranones with beta-alkoxy groups. The reaction works equally well with both amino acid- and carbohydrate-based alcohols. To demonstrate the utility of this process for carbohydrate chemistry several of the products were selectively converted into alpha-manno-pyranosides in two additional steps. Because the 2-substituted 6-carboxy-2H-pyran-3(6H)-ones are prepared by asymmetric synthesis, this reaction can be used for the preparation of either d- or l-pyranones.


[Clinical, radiologic and functional changes in the respiratory system and changes in cytology of bronchoalveolar lavage fluid of patients with idiopathic pulmonary fibrosis].
The course of the pulmonary fibrosis is difficult to estimate as there are no diagnostic tests specific and sensitive enough to assess disease activity. Together 33 patients with pulmonary fibrosis have been studied. They have been divided into 2 subgroups, depending on the intensity of clinical, radiologic, and functional disorders. In all patients bronchoalveolar lavage has been carried out, and the obtained results have been compared with those in 18 healthy individuals. Changes in the cellular composition of BAL fluid had polymorphic character. In the early phase of the disease, only percentage of lymphocytes in BAL fluid has been increased significantly whereas in the more advanced stage percentage of both neutrophils and eosinophils has also been significantly increased. The use of several parameters simultaneously helps to evaluate pulmonary fibrosis.


Plant secondary metabolites alter the feeding patterns of a mammalian herbivore (Neotoma lepida).
Mammalian herbivores are predicted to regulate concentrations of ingested plant secondary metabolites (PSMs) in the blood by modifying the size and frequency of feeding bouts. It is theorized that meal size is limited by a maximum tolerable concentration of PSMs in the blood, such that meal size is predicted to decrease as PSM concentration increases. We investigated the relationship between PSM concentration in the diet and feeding patterns in the herbivorous desert woodrat (Neotoma lepida) fed diets containing phenolic resin extracted from creosote bush (Larrea tridentata). Total daily intake, meal size and feeding frequency were quantified by observing the foraging behavior of woodrats on diets containing increasing concentrations of creosote resin. Desert woodrats reduced meal size as resin concentration in the diet increased, resulting in an overall reduction in daily intake and regulation of resin intake. Moreover, desert woodrats were able to detect resin concentrations in the diet and regulate the intake of resin very rapidly. We suggest that the immediate and sustained ability to detect and regulate the intake of resin concentrations during each foraging bout provides a behavioral mechanism to regulate blood concentrations of resin and allows desert woodrats to make "wise" foraging decisions.


Galactose Grafted Two-Dimensional Nanosheets as a Scaffold for the In Situ Synthesis of Silver Nanoparticles: A Potential Catalyst for the Reduction of Nitroaromatics.
Two major hurdles in NP-based catalysis are the aggregation of the NPs and their recycling. Immobilization of NPs onto a 2D support is the most promising strategy to overcome these difficulties. Herein, amphiphilicity-driven self-assembly of galactose-hexaphenylbenzene-based amphiphiles into galactose-decorated 2D nanosheet is reported. The extremely dense decoration of reducing sugar on the surface of the sheets is used for the in situ synthesis and immobilization of ultrafine catalytically active AgNPs by using Tollens' reaction. The potential of the system as a catalyst for the reduction of various nitroaromatics is demonstrated. Enhanced catalytic activity is observed for the immobilized AgNPs when compared to the corresponding discrete AgNPs. Recovery of the catalytic system from the reaction mixture by ultrafiltration and its subsequent recycling for several cycles without dropping its activity is shown. This is the first report demonstrating the in situ synthesis and immobilization of ultrafine AgNPs onto a 2D nanosheet that exhibits excellent catalytic performance for the reduction of nitroaromatics.


Stability of bacterial coaggregates in extreme environments.
The stability of coaggregates formed by the interaction of Acinetobacter johnsonii S35 and Oligotropha carboxidovorans S23, both of which are nonflocculating sludge bacteria, was evaluated by a spectrophotometric assay of aggregation index and phase contrast microscopy. Exposure of coaggregates to conditions of various pH (3-11) or temperature (10-5 degrees C) did not cause significant deflocculation and high aggregation index (85-93%) was still maintained as compared to 93.3% under normal conditions. Further, heat pretreatment of A. johnsonii S35 and O. carboxidovorans S23 cells at 60 or 80 degrees C did not prevent their subsequent coaggregation indicating that the interacting cell surface structures are heat-resistant. However, dual exposure of coaggregates to low temperature (10 degrees C) and extreme pH caused disruption of coaggregates coupled with the reduction in aggregation index below 28% (pH 3) and 49% (pH 11). Use of sterile filtrate of settled sewage (SFSS) in place of electrolyte solution as coaggregating medium produced usual large coaggregates (above 100 microm) indicating reproducibility of this coaggregation in sewage treatment plants. SFSS coaggregates incurred lesser deflocculation (50 and 85%, respectively) at extreme pH (3 and 11, respectively) and low temperature. This study demonstrated that although bacterial coaggregates are strong and stable against individual pH or temperature stress, a dual stress might deteriorate the performance and quality of treated waters.


S100P expression in human esophageal epithelial cells: Human esophageal epithelial cells sequentially produce different S100 proteins in the process of differentiation.
Extracellular calcium ions (Ca(2+)) are important in regulating the differentiation of keratinocytes and squamous epithelial cells. To clarify the mechanisms involved in the differentiation of human esophageal epithelial cells (EECs), we used the primary culture of human EECs, which can be differentiated by increasing the concentration of extracellular Ca(2+), and tried to reveal the extracellular Ca(2+) inducible genes using a differential display (DD) method. We found that the calcium-binding protein S100P showed a Ca(2+)-inducible expression in the EECs. Our immunohistochemical study demonstrated that differentiated large EECs expressing S100P overlie immature proliferating cells which lack S100P immunoreactivity. S100P was detected in vivo in the suprabasal layers of the epithelium. These findings indicate that S100P expression is closely associated with differentiation of human EECs. We also investigated the expression of other S100 proteins, including S100A2, S100A6, and CAAF1 (S100A12), in human EECs. Most of the immature EECs were positive for S100A2 and S100A6, whereas the S100A12-producing cells were similar to the S100P-producing cells. In vivo, S100A12 was strongly detected on all epithelial cells except for basal and proliferating cells. S100A2 was detected on all of the epithelial cells. S100A6 was preferentially seen in the cells of basal layers. These findings suggest that within EECs S100 proteins might play important roles in cell differentiation during specific stages. Among them, S100P expression is unique in that this protein is transiently expressed during the early stage of differentiation.


Binding of disopyramide to alpha 1-acid glycoprotein in plasma measured by competitive equilibrium dialysis.
A modification of equilibrium dialysis in which alpha 1-acid glycoprotein and plasma compete directly for disopyramide has been used in conjunction with binding curves to measure the extent of the alpha 1-acid glycoprotein-disopyramide interaction. At concentrations in the therapeutic range, 80-90% of disopyramide was bound to alpha 1-acid glycoprotein for plasma from each of six healthy adults. Also, equilibrium dialysis data are presented, indicating that pH does not influence the binding of disopyramide within the therapeutic range.


Common-source epidemic of hepatitis due to glazed and iced pastries.
Sixty-one clinical cases of hepatitis occurred in Ogemaw County, Michigan, in late April and May 1968. The clustering of cases in time and the high attack rate for persons 10-19 years of age suggested a common source of exposure. Investigation implicated a local bakery, where one of the employees directly involved in the baking had had an icteric illness one month before the outbreak. Comparison of exposure histories of patients versus healthy family members established pastries covered with glaze or icing as the vehicle of infection. The glaze and icing were applied to the pastries after all baking had been completed. During the epidemic, immune serum globulin was given on a community-wide basis. No secondary cases of hepatitis were identified.


[The effect of nooglutil and piracetam on different forms of operant learning].
We studied effects of a new drug with nootropic action nooglutil (N-(5-hydroxynicotinoil)-L-glutaminic acid, OHK-10) on initial stages of different forms of operant behaviour in rats, namely avoidance learning in Shuttle box, in Skinner box and on T-maze reflex with water reward. Comparing dates resulted from these three methods permitted evaluation of effects of the drugs on learning. Both drugs had no effects on avoidance response in shuttle box and T-maze reflex with water reward. Nooglutil enhanced escape and avoidance responses meanwhile piracetam improved only escape response.


Time-dependent perpendicular fluctuations in the driven lattice Lorentz gas.
We present results for the fluctuations of the displacement of a tracer particle on a planar lattice pulled by a step force in the presence of impenetrable, immobile obstacles. The fluctuations perpendicular to the applied force are evaluated exactly in first order of the obstacle density for arbitrarily strong pulling and all times. The complex time-dependent behavior is analyzed in terms of the diffusion coefficient, local exponent, and the non-Skellam parameter, which quantifies deviations from the dynamics on the lattice in the absence of obstacles. The non-Skellam parameter along the force is analyzed in terms of an asymptotic model and reveals a power-law growth for intermediate times.


Luminescent dirhenium(I)-double-heterostranded helicate and mesocate.
The semirigid ligands 1,4-bis(2-(2-hydroxyphenyl)benzimidazol-1-ylmethyl)benzene (H2-pBC) and 1,3-bis(2-(2-hydroxyphenyl)benzimidazol-1-ylmethyl)-2,4,6-trimethylbenzene (H2-mBC), containing two hydroxyphenylbenzimidazolyl units as bis-chelating (or bis(bidentate)) N∩OH donor, were synthesized and were used to assemble neutral, luminescent heteroleptic, unsaturated double-hetero-stranded, rhenium(I)-based helicate (1) and mesocate (2) with the flexible bis(monodentate) nitrogen donor (1,4-bis(benzimidazol-1-ylmethyl)benzene/1,3-bis(benzimidazol-1-ylmethyl)benzene), and Re2(CO)10. The photophysical properties of the complexes were studied. Both complexes 1 and 2 exhibit dual emissions in both solution and solid state. In solution, these complexes show both fluorescence and phosphorescence. Complex 1 undergoes a predominantly ligand-centered oxidation, resulting in the generation of phenoxyl radicals.


βB2-Crystallin Promotes Axonal Regeneration in the Injured Optic Nerve in Adult Rats.
The purpose of the study was to further scrutinize the potential of βB2-crystallin in supporting regeneration of injured retinal ganglion cell axons both in vitro and in vivo. Retinal explants obtained from animals after treatment either with lens injury (LI) alone or with combined LI 5 days or 3 days before or simultaneously with an optic nerve crush (ONC) were cultured for 96 h under regenerative conditions, and the regenerating axons were quantified and compared with untreated controls. These measurements were then repeated with LI replaced by intravitreal injections of γ-crystallin and β-crystallin at 5 days before ONC. Finally, βB2-crystallin-overexpressing transfected neural progenitor cells (βB2-crystallin-NPCs) in the eye were studied after crushing the optic nerve in vivo. Regeneration was monitored with the aid of immunoblotting of the retina and optic nerve both distal and proximal to the lesion site, and this was compared with controls that received injections of phosphate buffer only. LI performed 5 days or 3 days before ONC significantly promoted axonal outgrowth in vitro (p < 0.001), while LI performed alone before explantation did not. Intravitreal injections of β-crystallin and γ-crystallin mimicked the effects of LI and significantly increased axonal regeneration in culture at the same time intervals (p < 0.001). Western blot analysis revealed that crystallins were present in the proximal optic nerve stump at the lesion site in ONC, but were neither expressed in the undamaged distal optic nerve nor in uninjured tissue. βB2-crystallin-NPCs supported the regeneration of cut optic nerve axons within the distal optic nerve stump in vivo. The reported data suggest that βB2-crystallin-producing "cell factories" could be used to provide novel therapeutic drugs for central nervous system injuries.


Histological evaluation of radiochemotherapy for prostatic cancer: early results of a pilot study.
Antiandrogen therapy has been widely used for prostatic cancer, yet many authors have reported on the limited efficacy of hormonal therapy for this disease. The present report is based on an histological evaluation of chemotherapy and radiotherapy in combination for prostatic cancer. To determine the usefulness of this combined therapy, 15 prostatic cancer patients were treated with a combination of Bleomycin and Adriamycin (BA therapy), or with only Adriamycin. Radiotherapy was administered to all cases. Twelve of the 15 patients were evaluable histologically with effects ranging from Grade I to Grade IV in Shimosato's classification. We conclude that further investigation, including a randomized study of hormonal therapy, is necessary.


Available amino acid score for evaluating protein quality of foods.
Amino acid scores corrected for true digestibility of individual amino acids (as determined by rat balance method) were termed "available amino acid scores" in the present investigation. Available amino acid scores were calculated for 7 protein sources and their 10 supplementary or complementary mixtures which have been tested in collaborative amino acid and rat growth assays for evaluating protein quality. The available amino acid scores were as follows: casein + methionine (100); egg white (100); rapeseed protein concentrate, RPC (94); casein (93); beef (89); soya assay protein, SAP (62); pea flour (61); whole wheat flour, WW (38); SAP + methionine (88); pea flour + methionine (72); WW + lysine (67); WW + casein (84); WW + egg white (79); WW + RPC (65); WW + beef (77); WW + SAP (70); and WW + pea flour (75). These scores were similar to the collaborative relative NPR values; the differences were less than 10 units (2-9 units) in most cases. The positive correlation (r = 0.92) between available amino acid scores and relative net protein ratio (RNPR, a rat growth method) values was highly significant (P less than 0.01) and the origin of the regression line (y = 0.92x + 1.88) was not significantly different from zero. Amino acid bioavailability has previously been a problem, preventing widespread acceptance of amino acid score. Available amino acid score solves this problem.


Sport, Society, and Anti-Doping Policy: An Ethical Overview.
The purpose of this chapter is to provide an overview of the philosophical and ethical underpinnings of anti-doping policy. The nature of sport and its gratuitous logic is explored. The doping rules in sport, such as the Prohibited List, are ways of drawing a line to facilitate a certain sort of competition. Sports can be understood as a means of testing the natural physical abilities of the athlete, combined with the hard work they put into improving their performance. A test promoted by the anti-doping laws. Permitting certain forms of performance enhancement would threaten the special nature of such a test. Doping can be seen as a threat to the integrity of sport, not just because of the rule breaking doping currently entails. The chapter explores the ethical issues that arise with such forms of enhancement, such as fairness, harms to health, and indeed a refusal to accept human limitations. Finally, the criteria upon which a substance or method may be prohibited by the World Anti-Doping Agency (WADA) is addressed. The 3-part criteria, concerning (1) enhancement, (2) health, and (3) the spirit of sport are described, and literature that takes a critical line is addressed. Particular reference is made to the public health agenda explicit within anti-doping policy.


Inferences about the location of food in the great apes (Pan paniscus, Pan troglodytes, Gorilla gorilla, and Pongo pygmaeus).
Bonobos (Pan paniscus; n = 4), chimpanzees (Pan troglodytes; n = 12), gorillas (Gorilla gorilla; n = 8), and orangutans (Pongo pygmaeus; n = 6) were presented with 2 cups (1 baited) and given visual or auditory information about their contents. Visual information consisted of letting subjects look inside the cups. Auditory information consisted of shaking the cup so that the baited cup produced a rattling sound. Subjects correctly selected the baited cup both when they saw or heard the food. Nine individuals were above chance in both visual and auditory conditions. More important, subjects as a group selected the baited cup when only the empty cup was either shown or shaken, which means that subjects chose correctly without having seen or heard the food (i.e., inference by exclusion). Control tests showed that subjects were not more attracted to noisy cups, avoided shaken noiseless cups, or learned to use auditory information as a cue during the study. It is concluded that subjects understood that the food caused the noise, not simply that the noise was associated with the food.


Cloning and expression of human V-genes derived from phage display libraries as fully assembled human anti-TNF alpha monoclonal antibodies.
With the advent of phage antibody libraries, access to completely human antibody fragments is feasible, either by direct selection from human antibody libraries, or by guided selection. After selection, Fabs and scFvs may need to be expressed as complete antibodies in mammalian cells for further characterisation, or if effector functions are required. To rebuild and express the human anti-TNF alpha antibody Fab-P3A2 (isolated as a Fab fragment from phage display libraries by guided selection) as a fully assembled, functional human antibody (gamma-1, lambda) in Sp2/0 myeloma cells, and to perform preliminary characterisation studies of the secreted IgG1 molecule. A further objective was to investigate the kinetics of human antibody production and the stability of antibody secretion in transfectomas cultured in various media formulations. A tripartite strategy was employed for cloning heavy chain gene (VH)-P3 and light chain gene V lambda-A2-C lambda into mammalian cell expression vectors p alpha Lys-30 and p alpha Lys-17 respectively. The cell line P3A2.B5 was isolated after co-transfection of Sp2/0 mouse myelomas with the constructs, expanded and weaned into a protein free medium. Fully assembled Ig-P3A2 antibody was purified by Protein A affinity chromatography and characterised with respect to size of antibody chains, and affinity for human TNF alpha. Stability of secretion was investigated by extended serial sub-culture and analysis of P3A2.B5 sub-clones. Strategies of media enrichment were tested for any effect on antibody productivity by selected P3A2.B5 sub-clones. The cell line P3A2.B5 secreted an assembled, human antibody Ig-P3A2, with heavy and light chains of molecular weight 55 and 28 KD respectively. Equilibrium capture studies showed Ig-P3A2 to have a dissociation constant of approximately 1.5 x 10(-8) M. The mean specific productivity of the cell line increased from 1.2 pg/cell/day to 7.8 pg/cell/day by a combination of medium enrichment and serum reduction. Prolonged serial sub-culture of P3A2.B5 showed the cell line to be unstable with respect to antibody secretion. We have outlined a method for expression of human V genes as assembled antibodies in Sp2/0 myeloma cells. A cloning strategy for the stable expression of scFv or Fab genes isolated from phage display libraries as assembled human antibodies of the IgGl subclass in Sp2/0 myeloma cells has been described. For maximising specific productivity of antibody-producing cell lines, supplementation of culture media with glucose, glutamine and amino acids increases antibody yield significantly compared to that in conventional media, indicating the latter is stoichiometrically limiting for production purposes.


Nuclear Microprobe Mapping of Statoliths of Chokka Squid Loligo vulgaris reynaudii d'Orbigny, 1845.
Loliginid squid statoliths were broken in half and their elemental composition was assessed using the nuclear microprobe technique. Proton induced X-ray emission and proton backscattering were used simultaneously. True, quantitative maps of calcium and strontium distribution in the frontal plane were obtained using a rapid-matrix-transform method called Dynamic Analysis. These measurements were complemented by observations with scanning electron microscopy and light microscopy. In juvenile and adult statoliths, Sr was concentrated in the wing and adjacent areas, whereas the Ca concentration was highest on the edge of the lateral dome. In contrast, Sr and Ca were uniformly distributed in the statoliths of paralarval squid. Increments showed best definition in the areas anterior and adjacent to the wing, corresponding to areas of high Sr content. Although temperature, sex, maturity, and the administration of oxytetracycline may influence the quantitative distribution of Ca and Sr in the statoliths of adult squid, they do not appear to affect the general pattern described above. The finding that Sr is concentrated in regions adjacent to the macula where the clearest increments are found in loliginid statoliths supports the hypothesis linking strontium with the regulation of statolith deposition and the definition of daily increments.


Synthesis of beta-site amyloid precursor protein-cleaving enzyme 1 inhibitors BI 1147560 and BI 1181181 labeled with carbon-14 and deuterium.
The generation of amyloid beta peptides that aggregate in the brain is believed to play a major role in Alzheimer's disease. In theory, the inhibition of beta-site amyloid precursor protein-cleaving enzyme 1 (BACE1), which catalyzes the initial rate-limiting step in amyloid beta production, may slow or stop Alzheimer's disease. Herein, we report the preparation of two potent BACE1 inhibitors, BI 1147560 (1) and BI 1181181 (2), labeled with carbon-14 and with deuterium. The use of advanced key chiral intermediates like 3 and 5 shortened the carbon-14 syntheses of these two compounds to five and six steps, respectively, and helped in preparing them with very high chemical purity and enantiomeric excess without deviating from the process chemistry route. For the deuterium synthesis, oxetan-3-ylmethanamine [2 H6 ]-7 and 2-fluoro-2-methylpropan-1-amine [2 H6 ]-9 were prepared then used with the chiral intermediate 5 to furnish deuterium labeled 1 and 2, respectively.


[Adipose tissue in plastic surgery].
Current knowledge about adipose tissue is reviewed. Adipose tissue represents a special type of reticular connective tissue. Its full development is reached with the termination of body growth. The structural units of adipose tissue are fat lobules, the vascular supply of each lobule being complete and independent. Problems associated with fatty tissue surgery can be attributed to its structural and functional features. Pathophysiological processes in healing and transplantation of fatty tissue are analysed and correlated with clinical observations. The combination of fatty tissue properties does not favour free transplantation.


Budipine provides additional benefit in patients with Parkinson disease receiving a stable optimum dopaminergic drug regimen.
The complex pharmacological profile of the antiparkinsonian drug budipine influences neurotransmission beyond the dopaminergic system. Previous studies have demonstrated the therapeutic efficacy of budipine on motor symptoms in insufficiently treated patients with Parkinson disease. To demonstrate the efficacy of 20 mg of budipine, 3 times daily, in addition to a stable, prior, optimum-titrated dopaminergic substitution consisting of a combination of levodopa and a dopa decarboxylase inhibitor, bromocriptine mesylate, and optional selegiline hydrochloride in 99 patients with idiopathic Parkinson disease in a multicenter, double-blind, placebo-controlled trial. Budipine significantly (P<.001) decreased the Columbia University Rating Scale sum score (median, 15.0; 95% confidence interval, 11.3-17.0) compared with placebo (median, 4.3; 95% confidence interval, 3.0-7.5) at study end point. Budipine reduced Columbia University Rating Scale subscores for tremor, rigidity, and akinesia. The additional application of budipine provides further therapeutic benefit in subjects with Parkinson disease receiving a stable, prior, optimum-titrated dopaminergic drug regimen because of the hypothetical positive impact of budipine on altered nondopaminergic neurotransmission in patients with Parkinson disease.


Gender violence and psychopathology.
The focus of this article is to show that in Italy nowadays it is not important to relate psychopathology with violence. That is because it seems that it is more important to study gender and domestic violence as a social and cultural phenomenon than analyzing its psychopathological issues. Obviously, in accord with the literature there is a relationship about psychopatholgy and violence and this relationship concerns only about 5% of the total violence reported.


Bone metastasis from lung cancer identified by genetic profiling.
Cancer metastasis remains responsible for the vast majority of cases of cancer-related morbidity and mortality. Metastasis, by its definition, is the spread of cancer from the primary site to the distant tissues. Advancing the scientific and clinical understanding of cancer metastasis is a high priority. The prerequisite requirement for pathological consistency may be compromised during metastasis. The present study reports the case of a cancer patient with different pathological types. The patient presented with pain in the neck and right hip, as well as weight loss. He underwent whole-body positron emission tomography-computed tomography, which identified a mass in the lung and abnormal metabolism of the bone. Biopsies of the ilium and lung were performed and he was shown to have lung adenocarcinoma and bone squamous carcinoma. The morphology and immunohistochemical patterns were completely different, while each lesion harbored an identical genetic profile. The bone lesion was identified to be a metastasis from the lung cancer. The patient was prescribed an epithelial growth factor receptor inhibitor, which resulted in a partial response in the lung mass and alleviation of the patient's bone pain. Through this case study, we advocate the importance of using genetic testing in addition to pathological assessment.


Pin1 Modulation in Physiological Status and Neurodegeneration. Any Contribution to the Pathogenesis of Type 3 Diabetes?
Prolyl isomerases (Peptidylprolyl isomerase, PPIases) are enzymes that catalyze the isomerization between the cis/trans Pro conformations. Three subclasses belong to the class: FKBP (FK506 binding protein family), Cyclophilin and Parvulin family (Pin1 and Par14). Among Prolyl isomerases, Pin1 presents as distinctive feature, the ability of binding to the motif pSer/pThr-Pro that is phosphorylated by kinases. Modulation of Pin1 is implicated in cellular processes such as mitosis, differentiation and metabolism: The enzyme is dysregulated in many diverse pathological conditions, i.e., cancer progression, neurodegenerative (i.e., Alzheimer's diseases, AD) and metabolic disorders (i.e., type 2 diabetes, T2D). Indeed, Pin1 KO mice develop a complex phenotype of premature aging, cognitive impairment in elderly mice and neuronal degeneration resembling that of the AD in humans. In addition, since the molecule modulates glucose homeostasis in the brain and peripherally, Pin1 KO mice are resistant to diet-induced obesity, insulin resistance, peripheral glucose intolerance and diabetic vascular dysfunction. In this review, we revise first critically the role of Pin1 in neuronal development and differentiation and then focus on the in vivo studies that demonstrate its pivotal role in neurodegenerative processes and glucose homeostasis. We discuss evidence that enables us to speculate about the role of Pin1 as molecular link in the pathogenesis of type 3 diabetes i.e., the clinical association of dementia/AD and T2D.


[Analysis of 34 cases of systemic lupus erythematosus with decreased platelet count].
To explore the clinical and laboratory examination features of systemic lupus erythematosus (SLE) with decreased platelet count. Thirty-four SLE patients with decreased platelet count were analyzed for their initial symptoms, clinical manifestations, involvement of the organs and laboratory findings in comparison with 40 randomly selected SLE patients with normal platelet count. The SLE patients with decreased platelet count were more likely to develop kidney involvement than those with normal platelet, but the incidence of butterfly erythema was significantly lower in the former patients (PP<0.05). Some indices of laboratory examinations, such as CH(50), white blood cell reduction, rate of urine protein, thrombocytocrit and platelet distribution width were significantly higher in SLE patients with decreased platelet count than those with normal platelet count. The clinical manifestations and laboratory findings in SLE patients with decreased platelet count may differ from those of SLE patients with normal platelet.


History of current non-insulin medications for diabetes mellitus.
This article is a brief review of the current non-insulin agents for diabetes mellitus in the United States, namely, sulfonylureas, biguanides, thiazolidinediones, meglitinides, α-glucosidase inhibitors, glucacon-like peptide-1 receptor agonists, dipeptidyl-peptidase-4 inhibitors, amylin agonists, bromocriptine, and colesevelam.


Altered microRNA expression profile in exosomes during osteogenic differentiation of human bone marrow-derived mesenchymal stem cells.
The physiological role of microRNAs (miRNAs) in osteoblast differentiation remains elusive. Exosomal miRNAs isolated from human bone marrow-derived mesenchymal stem cells (BMSCs) culture were profiled using miRNA arrays containing probes for 894 human matured miRNAs. Seventy-nine miRNAs (∼8.84%) could be detected in exosomes isolated from BMSC culture supernatants when normalized to endogenous control genes RNU44. Among them, nine exosomal miRNAs were up regulated and 4 miRNAs were under regulated significantly (Relative fold>2, p<0.05) when compared with the values at 0 day with maximum changes at 1 to 7 days. Five miRNAs (miR-199b, miR-218, miR-148a, miR-135b, and miR-221) were further validated and differentially expressed in the individual exosomal samples from hBMSCs cultured at different time points. Bioinformatic analysis by DIANA-mirPath demonstrated that RNA degradation, mRNA surveillance pathway, Wnt signaling pathway, RNA transport were the most prominent pathways enriched in quantiles with differential exosomal miRNA patterns related to osteogenic differentiation. These data demonstrated exosomal miRNA is a regulator of osteoblast differentiation.


[Mapping sensitivity of surface waters to acidification in China].
Acidification of surface waters can be decided by some environmental factors, such as soil's buffering capacity, neutralization capacity of bedrock to acid deposition and types of land use, among which the most important factor is the soil's resistance to acidification. Therefore, information about soils, geology and land use can be used to predict the regional occurrence of acidification surface waters under different flows. In this paper, information and data about Chinese soils, geology and land use types were collected to determine and to map the sensitivity of surface waters to acidification. Results showed that in China, most surface waters were not sensitive to acidification. The few most sensitive surface waters were located in the north part of Northeastern China, accounting for 2.67% of all the country land. It was the combined results of strongly acidified ortho podzolic soil, acidified bedrock and coniferous forest. Surface waters which were not very sensitive to acidification were distributed both in the region of dark brown forest soil in Northeastern China and in the ferralsol and yellow-brown earth area in Southern China, occupying 15.2% of all the country land. The other surface waters which distributed on 82.11% of all the country land were not sensitive to acidification at all. Most in the Northern China because of the high resistance of soils to acidification and the others were in the Southern China where calcareous soils and agricultural lands were widely distributed. Since soils were quite resistant to acid, acidification of surface waters of large area will not likely occur in the southern region of China suffering from heavy acid deposition in the near future. Nevertheless, the acid deposition in Northern China should be controlled as soon as possible in case that acidified surface waters will be found there.


Two Haemophilus influenzae Rd genes that complement the recA-like mutation rec-1.
Two Haemophilus influenzae Rd genes each complemented the pleiotropic defects of the recA-like mutation rec-1. One gene, fec, was isolated on a 3.6-kilobase-pair EcoRI restriction fragment by complementation of the Fec- phenotype of bacteriophage lambda. The other gene, rec, was identified on a 3.1-kilobase-pair EcoRI fragment by Southern hybridization by using recA-like gene probes from Erwinia carotovora and Pseudomonas aeruginosa PAO. In a rec-1 strain of H. influenzae, the cloned genes restored resistance to UV irradiation, transformation by chromosomal DNA, and spontaneous release of HP1 prophage to wild-type levels. The fec and rec genes were located on the cloned segments by insertion and deletion mutagenesis and subcloning. The restriction endonuclease cleavage maps of the two DNAs were similar but not identical. Southern hybridization demonstrated that the two EcoRI restriction fragments contained homologous DNA sequences, but a fec gene-specific probe was prepared. Each gene encoded a 38,000-dalton polypeptide.


Rat microsomes and cytosol immobilized by microencapsulation in artificial cells.
Rat liver microsomes and cytosol have been co-immobilized by microencapsulation into artificial cells. The immobilized enzyme retained good enzyme activity. Enzyme kinetics, storage stability, pH profiles and temperature profiles have been analyzed.


Study of Structure and Mechanical Properties of Fine-Grained Aluminum Alloys Al-0.6wt.%Mg-Zr-Sc with Ratio Zr:Sc = 1.5 Obtained by Cold Drawing.
The thermal stability of a fine-grained (FG) aluminum wire has been studied in Al-0.6Mg-Zr-Sc alloys with various scandium and zirconium contents. Specimens were obtained by induction casting followed by cold deformation. The FG alloys have been demonstrated to have high thermal stability of the structure and properties due to the annealing pretreatment (320 °C, 2 h, before drawing), which results in deposition of Al₃(ScxZr1-x) intermetallic particles. It has been determined that following a prolonged annealing treatment (400 °C, 100 h), the alloys retain a uniform fine-grained structure with an average grain size of 2.4⁻2.8 μm whereas their microhardness measures 405⁻440 MPa.


Heterogeneity of aquaporin-4 localization and expression after focal cerebral ischemia underlies differences in white versus grey matter swelling.
Ischemic stroke, a major cause of mortality, is frequently accompanied by life-threatening cerebral edema. Aquaporin-4 (Aqp4), an astrocytic transmembrane water channel, is an important molecular contributor to cerebral edema formation. Past studies of Aqp4 expression and localization after ischemia examined grey matter exclusively. However, as white matter astrocytes differ developmentally, physiologically, and molecularly from grey matter astrocytes, we hypothesized that functionally important regional heterogeneity exists in Aqp4 expression and subcellular localization following cerebral ischemia. Subcellular localization of Aqp4 was compared between cortical and white matter astrocytes in postmortem specimens of patients with focal ischemic stroke versus controls. Subcellular localization and expression of Aqp4 was examined in rats subjected to experimental stroke. Volumetric analysis was performed on the cortex and white matter of rats subjected to experimental stroke. Following cerebral ischemia, cortical astrocytes exhibited reduced perivascular Aqp4 and unchanged Aqp4 protein abundance. In contrast, white matter astrocytes exhibited increased perivascular and plasmalemmal Aqp4 and a 2.2- to 6.2-fold increase in Aqp4 isoform abundance. Ischemic white matter swelled by approximately 40 %, while cortex swelled by approximately 9 %. The findings reported here raise the possibility that cerebral white matter may play a heretofore underappreciated role in the formation of cerebral edema following ischemia.


PCPP as a parenteral adjuvant for diverse antigens.
The adjuvanticity of the phosphazene polymer, poly[di(carboxylatophenoxy) phosphazene] (PCPP) was examined with a diverse collection of immunogens. PCPP proved to be a potent adjuvant for trivalent influenza virus vaccine, tetanus toxoid, hepatitis B surface antigen, herpes simplex virus glycoprotein gD2 and the capsular polysaccharide, polyribosylribitolphosphate, from Haemophilus influenzae type b. Taken together these results clearly demonstrate the general utility of PCPP as an adjuvant. Furthermore, PCPP was a superior adjuvant at least with TT compared to similar negatively charged polyanions, polymethylacrylic acid and polyacrylic acid.


Workshop on response criteria and evaluation of the stable disease category in carcinoma of the prostate, breast, and large bowel.
A multidisciplinary conference reviewed the clinical response criteria for the evaluation of stable disease category in a number of solid tumors, including prostate, breast, and large bowel cancer. Some similarities between the situation in hormonally responsive tumors, such as breast and prostate, were elucidated. With regard to bowel cancer, the principal site of metastases currently under evaluation is the liver site. Although ultrasound appears to be useful for following such lesions, it has also been shown that direct suturotomy is necessary. With regard to the overall situation involving the stable category, it was pointed out that, after due deliberation, for some solid tumors stable category may well be most important in that drugs that achieved this status may be otherwise discarded because of unprecise measurements. Greater accuracy in measurement and availability with current external diagnostic techniques were acknowledged and their applicability to certain situations was enumerated. It was also felt that there is a place, when documented, for the stable category, particularly prostate cancer. The reasons for this are discussed.


Experimental Measurement of Angular and Overlap Dependence of Conduction between Carbon Nanotubes of Identical Chirality and Diameter.
Measurement of the angular and overlap dependence of the conduction between two identical carbon nanotubes (CNTs), with the same diameter and chirality, has only been possible through theoretical calculations; however, our observation of increased resistance adjacent to the junction between two CNTs facilitates such measurements. Since electrical resistance was found to increase with increased diameter ratio, applying 10 V to one of dissimilar diameter CNTs results in cleavage at the junction. Manipulation of the resulting identical CNTs (created by cutting a single CNT) allows for the direct measurement of the angular and parallel overlap conduction. Angular (13° < θ < 63°) dependence shows two minima (22° and 44°) and a maximum at 30°, and conduction between parallel CNTs increases with overall tip separation but shows a sinusoidal relationship with contact length, consistent with the concept of atomic scale registry.


Water-soluble cyclodextrin polymers for enhanced relative recovery of hydrophobic analytes during microdialysis sampling.
Microdialysis relative recovery (RR) enhancement using different water-soluble, epichlorohydrin-based cyclodextrin polymers (CD-EPS) was studied in vitro for different analytes, amitryptiline, carbamazepine, hydroquinone, ibuprofen, and 4-nitrophenol. When compared to the native CDs (alpha, beta, and gamma) on a per mole basis, the CD-EPS enhanced microdialysis RR was either statistically greater or the same. beta-CD-EPS was more highly retained than native beta-CD by a 20 000 Da molecular weight cutoff (MWCO) polycarbonate membrane, but showed no statistical difference for loss across a 100 000 Da MWCO polyethersulfone membrane (PES). When the same weight percent of beta-CD or beta-CD-EPS was included in the microdialysis perfusion fluid, the beta-CD-EPS produced a higher microdialysis RR than native beta-CD for all analytes across the PES membrane. However, enhancements for the PC membrane were statistically insignificant when beta-CD and beta-CD-EPS were compared on a per mole basis. These results suggest that CD-EPS may be used as effective enhancement agents during microdialysis sampling and for some membranes provide the additional advantage of being retained more than native CDs.


[Critical observations on the rate of "False Negative" findings in gynecologic cytology (author's transl)].
In order to obtain a resonable approach to the rate of false negative findings in gynecologic cytology, all cases available to the authors for analysis with cervical carcinoma, carcinoma in situ and dysplasia during 1971 to 1973 were examined for any previous history of negative cytologic findings during the years preceding the detection of these pathologic conditions. It was found that negative results had been obtained in 11% of the patients suffering from cervical carcinoma, whereas the corresponding percentage figure was 18% negative results in carcinoma in situ patients. However, in about half of the cases, repetition of the smear had been recommended. Among the possible causes of false negative cytologic findings, the laboratory error (screening and evaluation) is the only one which can be accurately determined; in the present analysis, one-third of the false findings were found to be due to laboratory error. It is probable that the majority of the other false negative cytologic findings are mainly due to errors in sampling. As a matter of fact, rapidly growing carcinomas and carcinomas in situ are probably rare.


Biogas production potential of aquatic weeds as the next-generation feedstock for bioenergy production: a review.
Aquatic weeds have exceptionally high reproduction rates, are rich in cellulose and hemicellulose, and contain a negligible amount of lignin, making them an ideal crop for the next generation of biofuels. Previously reported studies proposed that water hyacinth, water lettuce, common duckweeds, and water spinach can be managed or utilized using different advanced techniques; from them, anaerobic digestion is one of the feasible and cost-effective techniques to manage these biowastes. The present study was carried out to investigate the potential of utilizing four common aquatic weed species (water hyacinth, water lettuce, common duckweeds, and water spinach) as substrates for anaerobic digestion in order to produce biogas for use in biofuels. The high reproduction rates and high cellulose and hemicellulose content, coupled with low lignin content, of these aquatic weeds make them ideal candidates for this purpose. The study evaluated the feasibility of using anaerobic digestion as a management technique for these aquatic weeds, which are often considered invasive and difficult to control. The results from various studies indicate that these aquatic weeds are productive feedstock options for anaerobic digestion, yielding a high biogas output. Among the aquatic weeds studied, water hyacinth, water lettuce, and common duckweeds exhibit higher methane production compared to water spinach. The study provides an overview of the characteristics and management strategies of these aquatic weeds in relation to biogas production, with possible future developments in the field.


The genetic basis of animal behavioural diversity in natural populations.
Individual differences in animal behaviour influence ecological and evolutionary processes. Much behavioural variation has a heritable component, suggesting that genetics may play a role in its development. Yet, the study of the mechanistic description linking genes to behaviour in nature remains in its infancy, and such research is considered a challenge in contemporary biology. Here, we performed a literature review and meta-analysis to assess trends in analytical approaches used to investigate the relationship between genes and behaviour in natural systems, specifically candidate gene approaches, quantitative trait locus (QTL) mapping, and genome-wide association studies (GWAS). We aimed to determine the efficacy and success of each approach, while also describing which behaviours and species were examined by researchers most often. We found that the majority of QTL mapping and GWAS results revealed a significant or suggestive effect (Zr = 0.3 [95% CI: 0.25:0.35] and Zr = 0.39 [0.33:0.46], respectively) between the trait of interest and genetic marker(s) tested, while over half of candidate gene accounts (Zr = 0.16 [0.11:0.21]) did not find a significant association. Approximately a third of all study estimates investigated animal personality traits; though, reproductive and migratory behaviours were also well-represented. Our findings show that despite widespread accessibility of molecular approaches given current sequencing technologies, efforts to elucidate the genetic basis of behaviour in free-ranging systems has been limited to relatively few species. We discuss challenges encountered by researchers, and recommend integration of novel genomic methods with longitudinal studies to usher in the next wave of behavioural genomic research.


Bis(3)-tacrine inhibits the sustained potassium current in cultured rat hippocampal neurons.
Bis(3)-tacrine is a dimeric AChE inhibitor derived from tacrine with a potential to treat Alzheimer's disease. It was recently been reported to act as a fast off-rate antagonist of NMDA receptors with moderate affinity. In the present study, we aimed to explore whether bis(3)-tacrine could modulate the function of native sustained potassium current in cultured rat hippocampal neurons using whole-cell patch-clamp technique. We found that bis(3)-tacrine inhibited the amplitude of sustained potassium current in a reversible and concentration-dependent manner, with a potency two orders of magnitude higher than that of tacrine. The inhibition was voltage-independent between 0 to +60 mV. The IC(50) values for bis(3)-tacrine and tacrine inhibition of sustained potassium current were 0.45+/-0.07 and 50.5+/-4.8 microM, respectively. I-V curves showed a more potent inhibition of sustained potassium current by bis(3)-tacrine (1 microM) compared to tacrine at the same concentration. Bis(3)-tacrine hyperpolarized the activation curve of the current by 11.2 mV, albeit leaving the steady-state inactivation of the current unaffected.


Surfactant phospholipids and proteins are increased in fetal sheep with pulmonary hypertension secondary to fetal systemic arteriovenous fistula.
To determine whether prenatal surfactant storage was altered in a model of systemic arteriovenous fistula (SAVF) with pulmonary hypertension, a fistula was created between the internal jugular vein and the carotid artery in 120-day fetal lambs, and surfactant material was explored at 134 days. Total phospholipids (TPL) and disaturated phosphatidylcholine (DSPC) were increased in whole lung tissue. Phospholipid analysis of isolated lamellar body fraction evidenced a specific increase of surfactant pool size: TPL and DSPC in this fraction were enhanced 1.9 and 2.9 times, respectively, when referred to DNA. Although the steady-state level of transcripts of surfactant protein (SP)-A and SP-B was not found to be changed at the time of death, semiquantitative Western blot analysis revealed elevated SP-A and SP-B protein contents three- and twofold, respectively. These findings indicate markedly enhanced accumulation of surfactant material in the presence of surgically induced prenatal pulmonary hypertension. Although total lung cell number was increased by 26%, SP-B immunolabeling indicated that increased surfactant amount did not result from an increased alveolar type II cell proportion, but rather from an increased rate of storage. Whether similar changes in surfactant are encountered in human neonates with persistent pulmonary hypertension is worthy of investigation.


Experience with a Multinational, Secondary School Education Module with a Focus on Prevention of Virus Infections.
Worldwide, virus infections are responsible for many diseases in terms of morbidity and mortality. Vaccinations and therapies are only available for relatively few virus infections and not always where they are needed. However, knowledge of transmission routes can prevent virus infection. In the context of this study, we measured the effects of a secondary school education module, named Viruskenner, on knowledge, attitude, and risk behavior as these relate to virus infections. A nonrandomized intervention study was conducted between April and August 2015 to assess the effect of this 2-month education module on knowledge, attitude, and behavior of 684 secondary school students in the Netherlands, Suriname, and Indonesia. For the Netherlands, a control group of a further 184 students was added. Factor analysis was performed on questions pertaining to attitude and behavior. Comparative analyses between pre- and posttest per country were done using multiple linear regression, independent sample T-tests, and one-way analysis of variance. These showed a significant increase in knowledge about virus infections and the prevention of infectious diseases among the Dutch and Surinamese groups, whereas a trend of increased knowledge was evident among the Indonesian participants. The Dutch control group showed an overall decrease in knowledge. Regression analyses showed that there was a significant interaction effect between participation and time on knowledge, attitude, and awareness and behavior and risk infection. Attitudes improved significantly in the intervention group. Pearson correlation coefficients between knowledge, attitude, and behavior were found to be positive.


A compilation of total daily energy expenditures and body weights in healthy adults.
Measurements of total energy expenditure (TEE) by the doubly labeled water method were compiled from 22 studies to identify the range of variation and significant determinants of energy requirements in healthy adults. The 126 male and 173 female subjects (aged 18-78 y) were separated into four groups: athletes, Pima Indians, people in developing countries, and others. The groups differed significantly (P < 0.001) with respect to TEE, TEE/BMR, TEE-BMR divided by weight, and TEE-BMR. Stepwise multiple regression demonstrated that fat-free mass (FFM) and age are significant variables that can explain 65% of the variation in TEE. These data demonstrate that total daily energy expenditure varies dramatically among healthy, free-living adults. The relationship between body fatness and nonbasal energy expenditure was negative at high energy outputs but considerable variation in body fatness was present among sedentary individuals, suggesting that a low rate of nonbasal energy expenditure is a permissive factor for obesity.


Performance of purified antigens for serodiagnosis of pulmonary tuberculosis: a meta-analysis.
Serological antibody detection tests for tuberculosis may offer the potential to improve diagnosis. Recent meta-analyses have shown that commercially available tests have variable accuracies and a limited clinical role. We reviewed the immunodiagnostic potential of antigens evaluated in research laboratories (in-house) for the serodiagnosis of pulmonary tuberculosis and conducted a meta-analysis to evaluate the performance of comparable antigens. Selection criteria included the participation of at least 25 pulmonary tuberculosis patients and the use of purified antigens. Studies evaluating 38 kDa, MPT51, malate synthase, culture filtrate protein 10, TbF6, antigen 85B, alpha-crystallin, 2,3-diacyltrehalose, 2,3,6-triacyltrehalose, 2,3,6,6'-tetraacyltrehalose 2'-sulfate, cord factor, and TbF6 plus DPEP (multiple antigen) were included in the meta-analysis. The results demonstrated that (i) in sputum smear-positive patients, sensitivities significantly >or=50% were provided for recombinant malate synthase (73%; 95% confidence interval [CI], 58 to 85) and TbF6 plus DPEP (75%; 95% CI, 50 to 91); (ii) protein antigens achieved high specificities; (iii) among the lipid antigens, cord factor had the best overall performance (sensitivity, 69% [95% CI, 28 to 94]; specificity, 91% [95% CI, 78 to 97]); (iv) compared with the sensitivities achieved with single antigens (median sensitivity, 53%; range, 2% to 100%), multiple antigens yielded higher sensitivities (median sensitivity, 76%; range, 16% to 96%); (v) in human immunodeficiency virus (HIV)-infected patients who are sputum smear positive, antibodies to several single and multiple antigens were detected; and (vi) data on seroreactivity to antigens in sputum smear-negative or pediatric patients were insufficient. Potential candidate antigens for an antibody detection test for pulmonary tuberculosis in HIV-infected and -uninfected patients have been identified, although no antigen achieves sufficient sensitivity to replace sputum smear microscopy. Combinations of select antigens provide higher sensitivities than single antigens. The use of a case-control design with healthy controls for the majority of studies was a limitation of the review. Efforts are needed to improve the methodological quality of tuberculosis diagnostic studies.


The influence of Zirconia and Fiber posts with different lengths on Fracture strength of Maxillary Central Incisors restored with zirconia crowns - An in vitro study.
Endodontically treated teeth are more susceptible to fractures than vital teeth because of significant coronal and radicular dentin loss during endodontic therapeutic procedures. The objective of this study was to estimate and compare the influence of length and post type on the fracture strength of endodontically treated maxillary central incisors. In this in vitro study, sixty extracted human maxillary central incisors were decoronated 2 mm above the cemento-enamel junction.They were selected and subjected to standard endodontic treatment ,resulting in preparation with lengths of 5 mm (group 5mm),7,5 mm (group 7,5 mm) and 10 mm (group 10mm). Each group was randomly divided into 2 subgroups according to the post type , zirconia and fiber post. After appropriate surface treatment,they were cementet with resin adhesive cement and restored with zirconia crowns. Thermocycling (5 -55°C, 60 seconds, 1500 cycles) was performed after cementing the zirconia crowns on each tooth. Prepared samples were subjected to compresive static load of 0.5mm / min, at an angle of 130° to the long axis of the roots, using Universal Testing Machine (Matest ) at an cross head speed of 0.5 mm / min, until fracture.The significance of the results was assessed using 2-way ANOVA and the Tukey-Kramer test (α=0.05) Results:The ANOVA analysis indicated significant differences (P<0.05) between the groups. Tukey test revealed no significant difference among the zirconia posts of 5-mm length (26.5 N ±13.4) 7,5-mm length (25.2 N ±13.9), and 10-mm length (17.1 N ±5.2). Also, in the fiber post group, there was no significant difference when posts of 7.5-mm length (13.4 N ±11.0) were compared with the 5-mm (6.9 N ±4.6) and 10-mm (31.7 N ±13.1) groups. The 10-mm long post displayed superior fracture strength, and the 5mm-long post showed significantly lower mean values (P<0.001). The fracture strength of zirconia posts (5-mm and 7,5- mm length)was found to be significantly higher than those of fiber posts (5-mm and 7,5- mm length). The 10-mm long fiberpost group demonstrated significantly higher values of fracture strengths and the 5-mm long fiberpost group showed the lowest values for the force resulting in root fracture; these groups were significantly different from each other (P<.001).The fracture strength analysis with Universal Testing Machine is the only method that enables us to estimate the differences between zirconia and fiber posts with different lengths on endodontically treated teeth.


Molecular Variants of HPV Type 16 E6 Among Honduran Women.
In this study, we investigated the prevalence of human papillomavirus 16 (HPV-16) variants in Honduran women with normal cytology and with dysplasia and cervical cancer. Samples identified as positive for HPV-16 by SPF10-LiPA were tested for intratypic subtypes and variants by analysis of the E6/E7 region using a novel reverse hybridization assay (line probe assay). We found that most infections in all clinical groups belong to the E6 European variants, suggesting that HPV-16 non-European variants do not represent an additional factor associated with increased occurrence of high-grade cervical lesions in the studied population. Among the 106 HPV-16-positive women analyzed, E-350G was the most prevalent variant in all different disease stages, being present in 18% of cervical cancer, 13% of cervical intraepithelial neoplasia grade III (CIN III), 5% of CIN II, 5% of CIN I, and 20% of control samples. Mixed variants of HPV-16 infections were detected in 7.7% of the samples, mostly in women with normal cytology. This study shows for the first time the diversity of HPV-16 variants in cervical samples of Honduran women.


Clozapine induces oxidative stress and proapoptotic gene expression in neutrophils of schizophrenic patients.
The present study examined cellular effects of the atypical antipsychotic drug clozapine on blood cells of treated patients with and without clozapine-induced agranulocytosis (CA). Blood from one patient who commenced clozapine treatment was examined at weekly intervals for 128 days. Olanzapine-treated (n = 5) and polymedicated (n = 14) schizophrenic patients, as well as healthy subjects (n = 19) and septic shock patients (n = 8), were studied for comparison. We observed dramatically increased numbers of native neutrophils stained for superoxide anion production (P < or = 0.005, n = 10) and significantly elevated expression levels of the proapoptotic genes p53 (P < or = 0.020), bax alpha (P < or = 0.001), and bik (P < or = 0.002) in all tested non-CA patients (n = 19) and CA patients (n = 4). In non-CA patients, the expression of these genes did not correlate to the percentage of apoptotic neutrophils (2.0% +/- 1.3%), but in CA patients about 37% of the neutrophils show morphologic signs of apoptosis (P < or = 0.001). Under G-CSF therapy of CA, the number of apoptotic neutrophils and the expression of the proapoptotic genes decreased significantly. In conclusion, high production of reactive oxygen species in neutrophils of clozapine-treated patients, together with increased expression of proapoptotic genes, suggests that neutrophils are predisposed to apoptosis in schizophrenic patients under clozapine therapy. The correlation between drug and proapoptotic markers was highest for clozapine and bax alpha as well as superoxide anion radicals. This indicates oxidative mitochondrial stress in neutrophils of clozapine-treated patients which probably contributes to the induction of apoptosis and sudden loss of neutrophils and their precursors in CA patients.


[Massive haematoma following rescue coronary angioplasty in a patient with acute myocardial infarction - a case report].
A case of a 79 year old female with acute myocardial infarction, treated with rescue coronary angioplasty, is presented. The patient received also thrombolysis, followed by heparin and IIb/IIIa platelet receptor blocker. The hospital stay was complicated by a massive groin haematoma and ecchymoses in the other parts of the lower and upper limbs, requiring blood transfusion.


Iterative C-H Functionalization Leading to Multiple Amidations of Anilides.
Polyaminobenzenes were synthesized by the ruthenium-catalyzed iterative C-H amidation of anilides using dioxazolones as an amino source. This strategy could be implemented by the sequential activation of C-H bonds of formerly generated compounds by cascade chelation assistance of newly installed amide groups. Computational studies provided a rationale.


Long-term remission of T-cell large granular lymphocyte leukemia associated with rheumatoid arthritis after rituximab therapy.
T-cell large granular lymphocyte leukemia (LGLL) is a rare clonal disease often associated with rheumatoid arthritis (RA) and manifests chiefly as neutropenia and recurrent infections. Immunosuppressive agents are the mainstay of treatment, but long-term remissions are rare. We report 2 cases of LGLL in patients with RA successfully treated with rituximab, a monoclonal antibody specific of B cells and approved for treating RA. The first patient experienced a complete LGLL remission that was sustained during the 8-year follow-up after the first rituximab infusion. In the second patient, rituximab therapy was followed by immediate neutropenia recovery and then by marked shrinkage of the LGLL clone 1 year later. The paradoxical efficacy of this specific anti-B-cell drug on a monoclonal T-cell disease suggests that some cases of LGLL may be reactive manifestations of chronic autoantigen stimulation rather than true malignancies.


The state of accommodation during the measurement of axial chromatic aberration of the eye.
The axial chromatic aberration of the eye was determined as in previous studies by finding the lens required to eliminate or minimize blur of the fixation target when it is illuminated by a series of monochromatic sources. Objective measurement of the refraction of the eyes during this procedure showed that accommodation remained constant throughout. Hence, the conclusion that the accommodative state does not in this case respond automatically to changes in the vergence of light falling in the retinal plane. It is suggested that some other stimulus, perhaps perceived distance, predominates. Further, the least amount of plus lens required to blur a near target was about the same for white and red but much less for blue. This substantiates an earlier finding that the eye accommodates for near only sufficiently to place the blue end of the chromatic interval on the retina.


Identification and association of RAC1 gene polymorphisms with mRNA and protein expression levels of Rac1 in solid organ (kidney, liver, heart) transplant recipients.
The activation of Ras-related C3 botulinum toxin substrate 1 (Rac1) is critical in the renal, hepatic and cardiac diseases that lead to the requirement for transplantation, however, no investigations have been performed in Chinese populations to determine the association between RAC1 genotypes and the activation of Rac1. In the present study, 304 solid organ transplant recipients (SOTRs), consisting of 164 renal transplantations, 85 hepatic transplantations and 55 cardiac transplantations, and 332 Chinese healthy control subjects were recruited to investigate whether differences existed in the mRNA and protein expression levels of Rac1 in the different groups. Furthermore, the present study identified and investigated associations of the RAC1 (rs702482, rs10951982, rs702483 and rs6954996) genotypes with the mRNA expression levels of RAC1, and the protein expression levels of total Rac1 and active Rac1‑guanosine triphosphatase (GTP). It was identified that the healthy population had significantly higher levels of Rac1 and Rac1‑GTP, compared with the kidney, liver and heart transplantation populations (P<0.001 for all comparisons). Significant associations (P<0.05) were observed between the RAC1 genotypes and the expression levels of mRNA, Rac1 and Rac1‑GTP. However, the changes in the mRNA expression levels of RAC1 with genotypes were different from those of the proteins. The results of the present study represent the first, to the best of our knowledge, to report that Rac1 and Rac1‑GTP proteins can be downregulated in SOTRs, and that RAC1 genetic polymorphisms can potentially affect the mRNA expression of RAC1, and the protein expression of Rac1 and Rac1‑GTP. These results provide a foundation for further functional investigations to determine the biological and molecular functions of the RAC1 gene in SOTRs.


Potential P-glycoprotein pharmacokinetic interaction of telaprevir with morphine or methadone.
Telaprevir (TVR) effects on P-glycloprotein and cytochrome P450 (CYP) may significantly elevate serum levels of morphine and methadone. Recent literature points to major interactions when combining TVR with warfarin or rifampin. Opioid interactions are especially dangerous in hepatitis C patients, as coinfection with human immunodeficiency virus (HIV) and hepatitis C virus (HCV) occurs in 50-90% of HIV-infected drug users that are prescribed opioids for chronic pain and/or methadone for maintenance. TVR has been shown to significantly inhibit the active transport enzyme pGP and may therefore increase intestinal morphine absorption. TVR also inhibits hepatic CYP3A4 that are responsible for metabolizing methadone. Patients requiring opioid analgesics must be carefully monitored because of potential for elevated opioid levels and overdose risk. Current recommendations minimize potential drug interactions between telaprevir and opioids, especially methadone, based on a single 7-day trial. We outline the various pharmacokinetic mechanisms involved when combining TVR with methadone or morphine and recommend that current data are not sufficiently robust to minimize the potentially significant interaction with opioids, especially methadone. Clinicians must be mindful of these understated interactions, know that the opioid dose may need to be significantly increased or reduced, and use caution during upward titration of opioids affected by these enzyme systems.


Activation of YAP regulates muscle fiber size in a PKC-dependent mechanism during chick in vitro myogenesis.
The formation of skeletal muscle fibers is an intricate process controlled by a multitude of signaling pathways, including Wnt, Shh, and FGF. However, the role of the Hippo pathway during vertebrate myofiber formation has conflicting reports, which we decided to address in chick muscle cultures. We found that the transcriptional regulator Yes-associated protein (YAP) was highly concentrated within the nuclei of myoblasts. As cells differentiate into myotubes, YAP localization shifted to the cell cytoplasm in more mature myotubes. Treatment of cultures with XMU-MP-1 (XMU), a MST1/2 inhibitor, stimulated the nuclear localization of YAP in myoblasts and in myotubes, upregulated myogenin, and promoted myoblast fusion, ultimately resulting in the formation of large and fully striated multinucleated myotubes. The XMU-induced phenotype was blocked by the protein kinase C (PKC) inhibitor calphostin, which raises the possibility that the Hippo pathway controls the growth of skeletal muscle fibers through a PKC-dependent mechanism.


Reaction and adaptation to the birth of a child: a couple-level analysis.
The present study explored how life satisfaction changes before and after childbirth among first-time parents from a nationally representative, longitudinal study of Germans. Life satisfaction increased before pregnancy to a peak just after birth and then returned to the baseline level within 2 years postpartum. The 2 members of the same couple reacted and adapted to childbirth in similar ways, suggesting that something about the event itself (rather than the individuals' personality) affects individual differences in these responses. However, some personality characteristics (including neuroticism and openness) did moderate reaction and adaptation effects.


Nardostachys chinensis induces granulocytic differentiation with the suppression of cell growth through p27(Kip1) protein-related G0/G1 phase arrest in human promyelocytic leukemic cells.
Nardostachys chinensis Batalin (Valerianaceae) has been used in Korean traditional medicine to elicit stomachic and sedative effects. However, the anti-leukemic activities of N. chinensis have not been well examined. To investigate the effect of N. chinensis on differentiation and proliferation in the human promyelocytic leukemic HL-60 cells. The dried roots and stems of N. chiensis are extracted using hot water and then freeze-dried. The yield of extract was 12.82% (w/w). The HL-60 cells were treated with 25-200 μg/ml of N. chinensis for 72 h or 100 μg/ml of N. chinensis for 24-72 h. Nardostachys chinensis significantly inhibited cell viability dose dependently with an IC50 of 100 μg/ml in HL-60 cells. Nardostachys chinensis induced differentiation of the cells as measured by reduction activity of NBT and expression of CD11b but not of CD14 as analyzed by flow cytometry, which indicates a differentiation toward the granulocytic lineage. Nardostachys chinensis also induced growth inhibition through G0/G1 phase arrest in the cell cycle of HL-60 cells. Among the G0/G1 phase in the cell cycle-related protein, the expression of cyclin-dependent kinase (CDK) inhibitor p27(Kip1) was increased in N. chinensis-treated HL-60 cells, whereas the expression levels of CDK2, CDK4, CDK6, cyclin D1, cyclin D3, cyclin E, and cyclin A were decreased. Interestingly, N. chinensis markedly enhanced the binding of p27(Kip1) with CDK2 and CDK6. This study demonstrated that N. chinensis is capable of inducing cellular differentiation and growth inhibition through p27(Kip1) protein-related G0/G1 phase arrest in HL-60 cells.


CD8 T cell responses to myelin oligodendrocyte glycoprotein-derived peptides in humanized HLA-A*0201-transgenic mice.
Multiple sclerosis (MS) is a demyelinating inflammatory disease of the CNS. Though originally believed to be CD4-mediated, additional immune effector mechanisms, including myelin-specific CD8(+) T cells, are now proposed to participate in the pathophysiology of MS. To study the immunologic and encephalitogenic behavior of HLA-A*0201-binding myelin-derived epitopes in vivo, we used a humanized HLA-A*0201-transgenic mouse model. Eight HLA-A*0201-binding peptides derived from myelin oligodendrocyte glycoprotein (MOG), an immunodominant myelin self-Ag, were identified in silico. After establishing their relative affinity for HLA-A*0201 and their capacity to form stable complexes with HLA-A*0201 in vitro, their immunological characteristics were studied in HLA-A*0201-transgenic mice. Five MOG peptides, which bound stably to HLA-A*0201 exhibited strong immunogenicity by inducing a sizeable MOG-specific HLA-A*0201-restricted CD8(+) T cell response in vivo. Of these five candidate epitopes, four were processed by MOG-transfected RMA target cells and two peptides proved immunodominant in vivo in response to a plasmid-encoding native full-length MOG. One of the immunodominant MOG peptides (MOG(181)) generated a cytotoxic CD8(+) T cell response able to aggravate CD4(+)-mediated EAE. Therefore, this detailed in vivo characterization provides a hierarchy of candidate epitopes for MOG-specific CD8(+) T cell responses in HLA-A*0201 MS patients identifying the encephalitogenic MOG(181) epitope as a primary candidate.


Interleukin-6: structure-function relationships.
Interleukin-6 (IL-6) is a multifunctional cytokine that plays a central role in host defense due to its wide range of immune and hematopoietic activities and its potent ability to induce the acute phase response. Overexpression of IL-6 has been implicated in the pathology of a number of diseases including multiple myeloma, rheumatoid arthritis, Castleman's disease, psoriasis, and post-menopausal osteoporosis. Hence, selective antagonists of IL-6 action may offer therapeutic benefits. IL-6 is a member of the family of cytokines that includes interleukin-11, leukemia inhibitory factor, oncostatin M, cardiotrophin-1, and ciliary neurotrophic factor. Like the other members of this family, IL-6 induces growth or differentiation via a receptor-system that involves a specific receptor and the use of a shared signaling subunit, gp130. Identification of the regions of IL-6 that are involved in the interactions with the IL-6 receptor, and gp130 is an important first step in the rational manipulation of the effects of this cytokine for therapeutic benefit. In this review, we focus on the sites on IL-6 which interact with its low-affinity specific receptor, the IL-6 receptor, and the high-affinity converter gp130. A tentative model for the IL-6 hexameric receptor ligand complex is presented and discussed with respect to the mechanism of action of the other members of the IL-6 family of cytokines.


Identification of the autoantigen HB as the barrier-to-autointegration factor.
The HB autoantigen, a 10-kDa DNA-binding protein recognized by autoantibodies only when bound to DNA, was identified by two-dimensional electrophoresis. Silver-stained protein spots corresponding to the antigen were excised from two-dimensional electrophoresis gels, digested with trypsin, and analyzed by matrix-assisted laser desorption/ionization-reflectron time of flight and nano-electrospray ionization-ion trap/mass spectrometry. Data base search identified the HB antigen as the barrier-to-autointegration factor, a cellular protein implicated in the cellular cycle that blocks autointegration and promotes intermolecular integration of retrovirus such as the Moloney murine leukemia and the human immunodeficiency type 1 virus. The physicochemical characteristics described for these proteins, their ability to bind double-stranded DNA but not single-stranded DNA, and their nuclear localization confirm that HB and barrier-to-autointegration factor are the same protein.


Ovicidal activity of entomopathogenic hyphomycetes on Aedes aegypti (Diptera: Culicidae) under laboratory conditions.
The ovicidal activity of 21 hyphomycete fungi species against Aedes aegypti (L.) (Diptera: Culicidae) was tested. Fungi with ovicidal activity developed on high numbers of eggs (> or =70%) during 25 d of exposure. A clear ovicidal activity with low values of hatch (1.3-40%) was observed after 25 d of incubation with Isaria farinosa (Holm: Fries) Fries, Paecilomyces carneus (Duché & Heim) Brown & Smith, Paecilomyces marquandii (Massee) Hughes, Isaria fumosorosea (Wize), Metarhizium anisopliae (Metschnikoff) Sorokin, Penicillium sp., Paecilomyces lilacinus (Thom) Samson, Beauveria bassiana (Balsamo) Vuillemin, and Evlachovaea kintrischica Borisov & Tarasov. More than 63% of eggs hatched after 25-d exposures to 11 other fungi species deemed as ineffective. These are the first results to show the effects of entomopathogenic fungi against eggs of Ae. aegypti, and they suggest their potential as control agents of this vector.


Antibody-functionalized gold nanoparticles as tumor-targeting radiosensitizers for proton therapy.
This study aimed at developing antibody-functionalized gold nanoparticles (AuNPs) to selectively target cancer cells and probing their potential radiosensitizing effects under proton irradiation. AuNPs were conjugated with cetuximab (Ctxb-AuNPs). Ctxb-AuNP uptake was evaluated by transmission electron microscopy and atomic absorption spectroscopy. Radioenhancing effect was assessed using conventional clonogenic assay. Ctxb-AuNPs specifically bound to and accumulated in EGFR-overexpressing A431 cells, compared with EGFR-negative MDA-MB-453 cells. Ctxb-AuNPs enhanced the effect of proton irradiation in A431 cells but not in MDA-MB-453 cells. These data indicate, for the first time, that combining enhanced uptake by specific targeting and radioenhancing effect, using conjugated AuNPs, is a promising strategy to increase cell killing by protontherapy.


Upregulation of Fas/Fas ligand-mediated apoptosis by gossypol in an immortalized human alveolar lung cancer cell line.
Gossypol has wide antineoplastic effects in vitro, but its effects on human lung cancer have not been explored. To evaluate the activity of gossypol against alveolar cell lung cancer and to provide information on the mechanism of action, we examined the effects of gossypol on the proliferation of A549 cells indirectly using an XTT assay and on the distribution of cells within the phases of the cell cycle using flow cytometry. We also examined several factors that may affect apoptosis, including p53, p21/WAF1, Fas receptor, Fas ligand (FasL) and caspase 8 activity. The results showed that gossypol inhibited proliferation of A549 cells at a concentration of 0.5 micromol/L after 12 h treatment. The effect was both dose- and time-dependent by the induction of apoptosis without the effect of p53 and p21/WAF1. Upregulation of Fas/FasL, in association with the activation of downstream caspase 8 activity, was observed following treatment with gossypol. The Fas/FasL pathway accounted for 75% of gossypol-mediated apoptosis. We suggest that the Fas/FasL apoptotic system is the major pathway for gossypol-mediated apoptosis of A549 cells. Gossypol had no effect on the distribution of A549 cells within the phases of the cell cycle. In conclusion, gossypol inhibited A549 cells mainly by induction of the Fas/FasL apoptotic pathway, but not the p53 and p21/WAF1 pathway.


Dichlorodiazirine: a nitrogenous precursor for dichlorocarbene.
The reaction of 3-p-nitrophenoxy-3-chlorodiazirine with a 1.1:1.0:1.6 blend of tetrabutylammonium chloride, cesium chloride, and the ionic liquid 1-butyl-3-methylimidazolium chloride at 40-50 degrees C under vacuum at 1 mm.Hg produced a melt from which dichlorodiazirine distilled into a cold trap containing pentane at -70 degrees C over 6-7 h. Dichlorodiazirine, the first nitrogenous precursor for dichlorocarbene, was reasonably stable in the dark at 25 degrees C and efficiently generated the carbene upon photolysis.


Health departments' implementation of public health's core functions: an assessment of health impacts.
The purpose of this article was to investigate the relationship between state health agencies' adherence to the recommendations of the United State's Institute of Medicine's (IOM) report, "The Future of Public Health", and changes in their populations' health. Data were abstracted from agencies' plans, budgets, annual reports, etc. spanning a 5-year period. A comprehensive change in population health measure over the same period was drawn from the UnitedHealth Group's annual survey. Configurations, based on public health core functions, were established using linear regression and qualitative comparative analysis. The dependent variable was a holistic measure of change in a state population's health status. State agencies that most completely adopted a public health model emphasizing assessment, assurance and policy development also experienced significant improvements in their population health measures. State agencies that more completely adopted the IOM's public health core functions had a concomitant improvement in their populations' health statuses. Further research to explore if there is a causal link between adoption of the core functions and positive health impacts is warranted.


Angiogenesis, cell proliferation and apoptosis in progression of cervical neoplasia.
To investigate changes in angiogenesis, cell proliferation and apoptosis in the successive steps of cervical neoplasia and to analyze their interrelationship. A total of 182 cervical specimens, representing 12 normal epithelium, 33 cervical intraepithelial neoplasia (CIN) 1, 21 CIN 2, 30 CIN 3 and 86 squamous cell carcinomas, were evaluated. The microvessels were immunohistochemically labeled with CD34 antibodies. Computerized image analysis was used to evaluate microvessel density (MVD). The apoptotic cells were visualized by a terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling technique and proliferative cells by staining with Ki-67 antibodies. One-way analysis of variance showed that the MVD, Ki-67 labeling index and apoptotic index increased significantly with the progression of cervical neoplasia from normal epithelium, through CIN, to carcinoma (P <.001 for each index). All the indices, determined in all 182 cervical tissues, were significantly and positively associated with each other (P < .001 in all cases), with correlation coefficients ranging from .649 to .819. MVD in patients with recurrence or death was significantly higher than in disease-free patients (P < .05). The results suggest that tumor progression in the cervical epithelium is accompanied by angiogenesis and an increase in both cell proliferation and apoptosis. Angiogenesis may be a prognostic indicator in patients with squamous cell carcinoma of the cervix.


Hand washing.
Essential facts Antimicrobial resistance develops when the medicines are used inappropriately. Global estimates suggest that every year more than 700,000 people die from drug-resistant strains of common bacterial and viral infections, such as the human immunodeficiency virus, tuberculosis and malaria. If antimicrobial resistance continues to increase, this number could rise to ten million a year by 2050.


Effects of Shizhifang on NLRP3 Inflammasome Activation and Renal Tubular Injury in Hyperuricemic Rats.
Uric acid (UA) activates the NLRP3-ASC-caspase-1 axis and triggers cascade inflammatory that leads to hyperuricemic nephropathy and hyperuricemia-induced renal tubular injury. The original study aims to verify the positive effects of the traditional Chinese medicinal formula Shizhifang (SZF) on ameliorating the hyperuricemia, tubular injury, and inflammasome infiltration in the kidneys of hyperuricemic lab rats. Twenty-eight male Sprague-Dawley rats were divided into four groups: control group, oxonic acid potassium (OA) model group, OA + SZF group, and OA + Allopurinol group. We evaluated the mediating effects of SZF on renal mitochondrial reactive oxygen species (ROS) and oxidative stress (OS) products, protein expression of NLRP3-ASC-caspase-1 axis, and downstream inflammatory factors IL-1β and IL-18 after 7 weeks of animals feeding. SZF alleviated OA-induced hyperuricemia and inhibited OS in hyperuricemic rats (P < 0.05). SZF effectively suppressed the expression of gene and protein of the NLRP3-ASC-caspase-1 axis through accommodating the ROS-TXNIP pathway (P < 0.05). Our data suggest that SZF alleviates renal tubular injury and inflammation infiltration by inhibiting NLRP3 inflammasome activation triggered by mitochondrial ROS in the kidneys of hyperuricemic lab rats.


Unusual presentation of Nocardia abscessus infection in an immunocompetent patient.
Nocardia infections are being increasingly reported in both immunocompetent and immunocompromised patients. We describe a case of Nocardia abscessus infection with an atypical presentation in an immunocompetent patient. A previously healthy 47-year-old gentleman presented with hiccups and paroxysmal spasms. Imaging revealed a pulmonary nodule, for which he underwent surgical resection. Pathologic evaluation demonstrated evidence of local inflammation, with growth of Nocardia abscessus on tissue cultures. Nocardia abscessus may have atypical presentations in immunocompetent patients. Further research is needed to understand the factors leading to Nocardia infections in immunocompetent patients.


Acquired amegakaryocytic thrombocytopenic purpura (AATP): a study of autologous megakaryocyte progenitors and the effect of patients plasma on normal marrow megakaryocyte colony formation.
Megakaryocyte progenitors (Colony Forming Unit-Megakaryocyte, CFU-Mk) and the effect of plasma on megakaryocyte colony formation in normal human marrow (Plasma Factor Index-Megakaryocyte, PFI-Mk) were studied in six patients with acquired amegakaryocytic thrombocytopenic purpura (AATP) and in ten normal subjects. Assay was based on the method of Messner. In one AATP marrow culture four CFU-Mk were found, in the other two a single CFU-Mk were present, and in the remaining three samples no megakaryocyte colonies were observed. PFI-Mk in AATP patients was significantly higher than in normal subjects. No correlation was found between PFI-Mk and platelet count in either group. The results of this study indicate the presence of an intrinsic defect at the level of CFU-Mk in AATP marrow. PFI-Mk in AATP patients relate to changes in marrow megakaryocyte number rather than to peripheral blood platelet count.


Watasemycins A and B, new antibiotics produced by Streptomyces sp. TP-A0597.
Two novel antibiotics, watasemycins A and B, were isolated from the fermentation broth of an actinomycete strain. The producing strain TP-A0597 was isolated from the seawater sample collected in Toyama Bay, Japan and identified as Streptomyces sp. based on the taxonomic study. The new antibiotics were obtained by solvent extraction and chromatographic purification and spectroscopic analyses identified that they were new analogs of thiazostatins. Watasemycin possesses a methyl group at 5'-position of thiazostatin instead of a hydrogen atom. Watasemycins showed antibiotic activity against Gram-positive and negative bacteria and yeast.


Influence of Comorbidities and Airway Clearance on Mortality and Outcomes of Patients With Severe Bronchiectasis Exacerbations in Taiwan.
Bronchiectasis is characterized by systemic inflammation and multiple comorbidities. This study aimed to investigate the clinical outcomes based on the bronchiectasis etiology comorbidity index (BACI) score in patients hospitalized for severe bronchiectasis exacerbations. We included non-cystic fibrosis patients hospitalized for severe bronchiectasis exacerbations between January 2008 and December 2016 from the Chang Gung Research Database (CGRD) cohort. The main outcome was the 1-year mortality rate after severe exacerbations. We used the Cox regression model to assess the risk factors of 1-year mortality. Of 1,235 patients who were hospitalized for severe bronchiectasis exacerbations, 641 were in the BACI < 6 group and 594 in the BACI ≥ 6 group. The BACI ≥ 6 group had more previous exacerbations and a lower FEV1. Pseudomonas aeruginosa (19.1%) was the most common bacterium, followed by Klebsiella pneumoniae (7.5%). Overall, 11.8% of patients had respiratory failure and the hospital mortality was 3.0%. After discharge, compared to the BACI < 6 group, the BACI ≥ 6 group had a significantly higher cumulative incidence of respiratory failure and mortality in a 1-year follow-up. The risk factors for 1-year mortality in a multivariate analysis include age [hazard ratio (HR) 4.38, p = 0.01], being male (HR 4.38, p = 0.01), and systemic corticosteroid usage (HR 6.35, p = 0.001), while airway clearance therapy (ACT) (HR 0.50, p = 0.010) was associated with a lower mortality risk. An increased risk of respiratory failure and mortality in a 1-year follow-up after severe exacerbations was observed in bronchiectasis patients with multimorbidities, particularly older age patients, male patients, and patients with a history of systemic corticosteroid use. ACT could effectively improve the risk for 1-year mortality.


Transscleral visible/near-infrared spectroscopy for quantitative assessment of haemoglobin in experimental choroidal tumours.
To study the feasibility of using transscleral visible/near-infrared spectroscopy (Vis/NIRS) to estimate the content of haemoglobin in choroidal tumour phantoms of ex vivo porcine eyes. Thirty enucleated porcine eyes were prepared with a tumour phantom made by injecting a suspension of gelatine, titanium dioxide and human blood into the suprachoroidal space. The blood concentrations used were 2.5%, 25% and 50%, with 10 eyes in each group. Alternating Vis/NIRS measurements were taken over the phantom inclusion and on the opposite (normal) side of each eye. For statistical analysis, a genetic algorithm was utilized to suppress insignificant wavelengths in the spectra. The processed spectra were then used to build a regression model based on partial least squares regression and evaluated by twofold cross-validation. Ultrasonography revealed that all phantoms were localized within the suprachoroidal space with no penetration through the retina. The largest mean diameters of the phantoms with 2.5%, 25% and 50% blood were 15.5, 15.2 and 15.7 mm, respectively (p > 0.05). The largest mean thicknesses were 4.5, 4.5 and 4.8 mm, respectively (p > 0.05). Statistical analysis of the spectral data showed that it was possible to correctly discriminate between the normal side and the tumour phantom side of the eyes in 99.88% of cases. The phantoms could be correctly classified according to their blood concentrations in 99.42% of cases. This study demonstrates that transscleral Vis/NIRS is a feasible and accurate method for the detection of choroidal tumours and to assess the haemoglobin content in such lesions.


ABM Clinical Protocol #37: Physiological Infant Care-Managing Nighttime Breastfeeding in Young Infants.
A central goal of the Academy of Breastfeeding Medicine (ABM) is the development of clinical protocols for managing common medical problems that may impact breastfeeding success. These protocols serve only as guidelines for the care of breastfeeding mothers and infants and do not delineate an exclusive course of treatment or serve as standards of medical care. Variations in treatment may be appropriate according to the needs of an individual patient. The ABM empowers health professionals to provide safe, inclusive, patient-centered, and evidence-based care. Pregnant and lactating people identify with a broad spectrum of genders, pronouns, and terms for feeding and parenting. There are two reasons ABM's use of gender-inclusive language may be transitional or inconsistent across protocols. First, gender-inclusive language is nuanced and evolving across languages, cultures, and countries. Second, foundational research has not adequately described the experiences of gender-diverse individuals. Therefore, ABM advocates for, and will strive to use language that is as inclusive and accurate as possible within this framework. For more explanation, please read ABM Position Statements on Infant Feeding and Lactation-Related Language and Gender (https://doi.org/10.1089/bfm.2021.29188.abm) and Breastfeeding As a Basic Human Right (https://doi.org/10.1089/bfm.2022.29216.abm).


Virus isolation studies in an outbreak of porcine encephalomyelitis.
An outbreak of central nervous system disease affecting young pigs occurred in the fall of 1981 in eastern Ontario. A diagnosis of viral encephalomyelitis was made on pathological grounds and virus isolation studies were subsequently initiated to determine the causative agent. Cultural isolation procedures using several biological systems failed to detect virus in nervous tissues from affected animals. Direct extraction of similar tissues by combined biochemical and biophysical procedures yielded nonenveloped , spherical particles with a diameter of 30 nm and a buoyant density of 1.34 g/mL in CsCl. A tentative diagnosis of enterovirus infection was made on this basis.


The current state of bone and tissue banking in Australia.
The development of bone and tissue banking in Australia over the last decade is described and details of the administrative structure, donor and recipient testing protocols, allograft segment processing procedures, and internal audit safety arrangements are also provided. Demographic data concerning both the retrieval and dispersal of musculoskeletal allograft materials in Australia are also discussed. Current price schedules for a variety of allograft materials available in Australia are made available for international comparison.


Hypertension and age: clinical and biochemical correlates.
Plasma renin activity, aldosterone and norepinephrine levels were determined in 247 ambulatory hypertensive patients divided into young, middle aged, and old groups. PRA and the increase of PRA after furosemide were higher in the younger; NE was higher in the old group. Some relationships may be inherent in aging and not necessarily confined to hypertensives. This may explain discrepancies between reports by investigators who studied homogenous groups classified in different ways.


Lectin array-based strategies for identifying metastasis-associated changes in glycosylation.
Since 2005, lectin microarray technology has emerged as a relatively simple yet powerful technique for the comprehensive analysis of glycoprotein glycosylation. Lectin microarrays represent a new analytical method that can be used to explore the human glycome, a unique source of markers of diseases including cancer. The lectin microarray technology is a sensitive tool with the potential to allow high-throughput analysis of cancer-associated changes in glycosylation. This chapter describes the generation of a lectin-binding signature associated with metastatic primary breast tumours that have been resected, fixed, and embedded in paraffin. Procedures concerning sample and lectin microarray preparation are explained, alongside experimental considerations and approaches to data analysis.