Radiological findings of the urinary tract in hypospadias: a report of 110 cases.
One hundred and ten patients with hypospadias underwent excretory urography and micturating cysto-urethrography before surgical correction. Urographic studies revealed abnormalities in 50 patients (45%), mainly anomalies of ascent and rotation of the kidneys. None of these patients required corrective surgery. Voiding cysto-urethrography disclosed disease of the urinary tract in 65 of 110 patients (59%). Meatal stenosis was found in 38 patients and a rudimentary vagina or a prostatic utricle was revealed in 11 others. Vesico-ureteral reflux was present in 14 patients, seven of whom had meatal stenosis as well. Cystitis was found in eight and a stricture of the membraneous urethra in one patient. The voiding cysto-urethrogram is able to demonstrate functionally significant meatal stenosis, genital abnormalities and vesico-ureteral reflux. It can also serve as a useful baseline for comparison with postoperative studies. We therefore consider that it should be included in the preoperative work-up of every patient with hypospadias. Excretory urography, however, is perhaps indicated only in those with urinary tract infection, or in patients otherwise symptomatic.


Evolving indications for surgical intervention in patients with differences/disorders of sex development: Implications of deferred reconstruction.
Rare medical conditions are difficult to study due to the lack of patient volume and limited research resources, and as a result of these challenges, progress in the care of patients with these conditions is slow. Individuals born with differences of sex development (DSD) fall into this category of rare conditions and have additional social barriers due to the intimate nature of the conditions. There is also a lack of general knowledge in the medical community about this group of diverse diagnoses. Despite these limitations, progress has been made in the study of effective ways to care for patients who are born with chromosomal or anatomical differences of their internal reproductive organs or external genitalia. Advocacy groups have placed a spotlight on these topics and asked for a thoughtful approach to educate parents of newborns, medical providers, and the adolescents and young adults themselves as they mature.1 There is growing interest in the approaches to surgical reconstruction of the genitalia and the management of internal gonads, specifically the timing of procedures and the indications for those procedures.2 Advocates suggest deferring surgical procedures until the affected individual can participate in the decision-making process. This approach requires a roadmap for addressing the long-term implications of delayed surgical management. Presented here is a review of the specific issues regarding the complex management of the various categories of DSD.


Determinants of disulfiram acceptance among alcohol patients: a test of the theory of reasoned action.
The utility of disulfiram in the treatment of alcohol abuse has been limited by the high frequency with which clients refuse the regimen. The present study identified variables influencing disulfiram acceptance/rejection within the framework of the theory of reasoned action. Eighty male inpatients on an alcohol treatment unit completed a questionnaire operationalizing the components of the model. The theoretical components were then used to predict requests for the drug. Multiple regression analyses revealed significant correlations among components of the model consistent with the assumptions of the theory. In addition, significant differences were found between disulfiram requestors and rejectors in terms of behavioral and normative beliefs about the consequences of being placed on the drug. Implications of these results for the design of effective interventions are discussed.


Serum beta-secretase 1 (BACE1) activity as candidate biomarker for late-onset Alzheimer's disease.
Beta-secretase (BACE1) is a key enzyme in the formation of amyloid-β; its activity/concentration is increased in brain and cerebrospinal fluid of patients with late-onset Alzheimer's disease (LOAD). Since BACE1 was found also in blood, we evaluated its potential as peripheral biomarker. To this aim, serum BACE1 activity was assessed in 115 subjects with LOAD and 151 controls. We found that BACE1 changed across groups (p < 0.001) with a 25% increase in LOAD versus controls. High levels of BACE1 (IV quartile) were independently associated with the diagnosis of LOAD (OR 2.8; 1.4-5.7). Diagnostic accuracy was 76% for LOAD. Our data suggest that increased BACE1 activity in serum may represent a potential biomarker for LOAD. Additional studies are needed to confirm the usefulness of BACE1, alone or in combination with other markers, in discriminating patients and predicting LOAD onset and progression.


Distribution of fibronectin during the morphogenesis of the truncus.
The distribution of fibronectin during morphogenesis of the truncus has been studied in chick embryo hearts between days 4 and 10 of incubation. Fibronectin appears as a natural marker for some truncal cells and permits the visualization of the different processes of cell rearrangement which result in truncal morphogenesis. The mesenchymal cells involved in formation of the aorto-pulmonary septum and in formation of the arterial tunica media are intensely fluorescent for fibronectin. These cells present fibrillar deposits of fibronectin associated with their surfaces. Very little staining for fibronectin is observed in association with the anlage of the semilunar valves. Prospective adventitial cells are negative for fibronectin. The close association between the fluorescence and the surface of the cells involved in formation of the aorto-pulmonary septum and the arterial tunica media suggests that fibronectin may be implicated in the formation of both structures. The intensity and amount of the fluorescence staining decreases as morphogenesis of the truncus is completed. The decrease in fibronectin staining is suggested to be related to changes in cell phenotypic expression.


T2STIR preparation for single-shot cardiovascular magnetic resonance myocardial edema imaging.
Myocardial edema in acute myocardial infarction (AMI) is commonly imaged using dark-blood short tau inversion recovery turbo spin echo (STIR-TSE) cardiovascular magnetic resonance (CMR). The technique is sensitive to cardiac motion and coil sensitivity variation, leading to myocardial signal nonuniformity and impeding reliable depiction of edematous tissues. T2-prepared balanced steady state free precession (T2p-bSSFP) imaging has been proposed, but its contrast is low, and averaging is commonly needed. T2 mapping is useful but requires a long scan time and breathholding. We propose here a single-shot magnetization prepared sequence that increases the contrast between edema and normal myocardium and apply it to myocardial edema imaging. A magnetization preparation module (T2STIR) is designed to exploit the simultaneous elevation of T1 and T2 in edema to improve the depiction of edematous myocardium. The module tips magnetization down to the -z axis after T2 preparation. Transverse magnetization is sampled at the fat null point using bSSFP readout and allows for single-shot myocardial edema imaging. The sequence (T2STIR-bSSFP) was studied for its contrast behavior using simulation and phantoms. It was then evaluated on 7 healthy subjects and 7 AMI patients by comparing it to T2p-bSSFP and T2 mapping using the contrast-to-noise ratio (CNR) and the contrast ratio as performance indices. In simulation and phantom studies, T2STIR-bSSFP had improved contrast between edema and normal myocardium compared with the other two edema imaging techniques. In patients, the CNR of T2STIR-bSSFP was higher than T2p-bSSFP (5.9 ± 2.6 vs. 2.8 ± 2.0, P < 0.05) but had no significant difference compared with that of the T2 map (T2 map: 6.6 ± 3.3 vs. 5.9 ± 2.6, P = 0.62). The contrast ratio of T2STIR-bSSFP (2.4 ± 0.8) was higher than that of the T2 map (1.3 ± 0.1, P < 0.01) and T2p-bSSFP (1.4 ± 0.5, P < 0.05). T2STIR-bSSFP has improved contrast between edematous and normal myocardium compared with commonly used bSSFP-based edema imaging techniques. T2STIR-bSSFP also differentiates between fat that was robustly suppressed and fluids around the heart. The technique is useful for single-shot edema imaging in AMI patients.


Electron staining of the cell surface coat by osmium-low ferrocyanide.
In aldehyde-fixed liver and renal cortex of rat and mouse several variations of postfixation with osmium tetroxide plus potassium ferrocyanide ( FeII ) were tried. Depending on the ferrocyanide concentration different staining patterns were observed in TEM. -Osmium-High Ferrocyanide [40 mM (approximately 1%) OsO4 + 36 mM (approximately 1.5%) FeII , pH 10.4], stains membranes and glycogen. Cytoplasmic ground substance, mitochondrial matrices and chromatin are partially extracted, cell surface coats remain unstained. Membrane contrast, but extraction too, are higher with solutions containing cacodylate- than phosphate-buffer. -Osmium-Low Ferrocyanide [40 mM (approximately 1%) OsO4 + 2 mM (approximately 0.08%) FeII , pH 7.4], stains cell surface coats and basal laminae, but not glycogen, except for special cases. The trilaminar structure of membranes is poorly delineated. Signs of cytoplasmic extraction are not visible. The surface coat staining is stronger and more widespread with solutions containing phosphate- instead of cacodylate-buffer; it is enhanced by section staining with lead citrate. The cell surface coat stain does not traverse tight junctions nor permeate membranes.


"Psychic surgery".
After study of the literature and other available information, the American Cancer Society has found no evidence that "psychic surgery" results in objective benefit in the treatment of any medical condition. Lacking such evidence, the American Cancer Society strongly urges individuals who are ill not to seek treatment by psychic surgery. The following is a review and summary of material on "psychic surgery" in the American Cancer Society files as of May 31, 1989. Reference to that material by the Society does not imply agreement with its contents.


Potentiometric titration of polyhexamethylene biguanide hydrochloride with potassium poly(vinyl sulfate) solution using a cationic surfactant-selective electrode.
A potentiometric titration method using a cationic surfactant as an indicator cation and a plasticized poly(vinyl chloride) membrane electrode sensitive to the cationic surfactant is proposed for the determination of polyhexamethylene biguanide hydrochloride (PHMB-HCl), which is a cationic polyelectrolyte. A sample solution of PHMB-HCl containing an indicator cation (hexadecyltrimethylammonium ion, HTA) was titrated with a standard solution of an anionic polyelectrolyte, potassium poly(vinyl sulfate) (PVSK). The end-point was detected as a sharp potential change due to an abrupt decrease in the concentration of the indicator cation, HTA, which is caused by its association with PVSK. The effects of the concentrations of HTA ion and coexisting electrolytes in the sample solution on the degree of the potential change at the end-point were examined. A linear relationship between the concentration of PHMB-HCl and the end-point volume of the titrant exists in the concentration range from 2.0 x 10(-5) to 4.0 x 10(-4) M in the case that the concentration of HTA is 1.0 x 10(-5) M, and that from 1.0 x 10(-6) to 1.2 x 10(-5) M in the case that the concentration of HTA is 5.0 x 10(-6) M, respectively. The proposed method was applied to the determination of PHMB-HCl in some contact-lens detergents.


Bidirectional endoscopy in patients with fecal occult blood.
Current screening protocols for colorectal cancer depend primarily on fecal occult blood testing (FOBT). However, positive test results do not always indicate the presence of a colonic neoplasm. We reviewed the results of 100 consecutive bidirectional (upper and lower) endoscopic procedures performed to evaluate positive FOBT results. Patients were excluded if they presented with gross bleeding, a history of bowel lesions, or previous intestinal operations. There were 31 women and 69 men whose mean age was 51 years. Major abnormalities were found on esophagogastroduodenoscopy (n = 24), colonoscopy (n = 13), or both studies (n = 2). Active bleeding was manifested in two patients, (Barrett's ulcer, duodenal arteriovenous malformation). Two other patients had malignancy: One had a cecal adenocarcinoma and the other a gastric adenocarcinoma. Various benign lesions also were identified in the stomach including esophagitis (n = 8), ulcers/erosions (n = 8) varices (n = 5), and arteriovenous malformations (n = 2). Colonic pathology included polyps (n = 8), arteriovenous malformations (n = 3), and rectal varices (n = 1). Diverticulosis and hemorrhoidal disease were present in 29 and 16 patients, respectively, but were not considered to be likely sources of a positive FOBT. Positive FOBT results may indicate the presence of either upper or lower intestinal pathology, and bidirectional endoscopy is an efficient and accurate technique for the comprehensive evaluation of occult bleeding.


Cellular destruction following transmyocardial laser revascularization (TMR).
During transmyocardial revascularization, cellular destruction of cardiomyocytes occurs as a result of the high-energy laser. However, the features of myocardial cellular destruction are unclear. The present study was undertaken to examine the structural characteristics of cell death in the myocardium following transmyocardial revascularization. Myocardial specimens from 3 male patients who had died within 11 days following laser revascularization were collected within 1 h of death and were analyzed by immunohistochemistry and electron microscopy. For immunohistochemistry, antibodies to pro-apoptotic proteins CPP32 and BAX were used. Immunohistochemical examination demonstrated the presence of cells expressing both CPP32 and BAX along the laser channel. Electron microscopic analysis revealed that the lining surface of laser channels consisted of condensed acellular debris and dead cells. No endothelialization of channels was noted. The lumen of laser channels were surrounded by a rim of acellular debris with several outer concentric rims of cardiomyocytes showing features of cellular destruction. The present study identified features of both necrotic and apoptotic cellular death following laser revascularization.


The Twisted Benzo[ghi]-Perylenetriimide Dimer as a 3D Electron Acceptor for Fullerene-Free Organic Photovoltaics.
A series of twisted N,N-linked benzo[ghi]-perylenetriimide dimers (t-BPTI) with various lengths of the α-branched alkyl side chain at the six-membered imide ring position was designed, synthesized, and characterized. These compounds showed the low-lying LUMO energy level of -3.78 eV, which was similar to that of PC61 BM (-3.71 eV), but with intensive optical absorption in the range 350-500 nm. The twisted molecular geometry with two nearly perpendicular BPTI planes achieved a favorable nanoscale phase separation by relieving the self-aggregation of rigid BPTI units in blend films. The acceptor t-BPTI-3 unit with the longest alkyl side chains has been demonstrated to be an efficient electron acceptor in solution-processed bulk heterojunction organic photovoltaics (OPV), giving a power conversion efficiency of 3.68 % when using conjugated polymer PTB7-Th as the donor and without additional treatments.


The association between the respiratory tract microbiome and clinical outcomes in patients with COPD.
Though it has been widely accepted that infections of the respiratory tract is associated with aetiology of acute exacerbation of chronic obstructive pulmonary disease (AECOPD), more recent techniques have shown emerging evidence on the importance of alterations of diversity and composition of microbiota itself in the disease process. Specifically, these alterations is widely present in COPD patients from a variety of populations, and is associated with severity of disease, frequency of acute exacerbation, as well as prediction of exacerbation. In addition, the microbiota from respiratory tract contributes to disease mechanisms, and more recently have been shown to interact with gut microbiota in a bidirectional way. Therefore, updating progress in the field is crucial as it not only reveals potential underlying mechanisms of the disease, but also highlights the potential utilisation of microbiota as a biomarker for disease prediction and as a target for treatment. In this narrative review, we summarize current updates on microbiota dysbiosis in COPD, including techniques for sampling and analysis of microbiota, recent findings on the presence of microbiota dysbiosis and its correlation with clinical prediction and prognosis of the disease, as well as its potential roles in disease mechanisms. In addition, how gut-lung axis contributes to COPD progression is also discussed. Finally, we addressed the utilisation of prebiotic and probiotic treatment for COPD. Together, we hope to provide useful information to advocate the use of microbial parameters as important tools for diagnosis, treatment and long-term follow-up for COPD patients.


Pharmacokinetics and biodistribution of paclitaxel-loaded pluronic P105 polymeric micelles.
A novel polymeric micelle formulation of paclitaxel (PTX) has been prepared with the purpose of improving in vitro release as well as prolonging the blood circulation time of PTX in comparison to a current PTX formulation, Taxol injection. This work was designed to investigate the preparation, in vitro release, in vivo pharmacokinetics and tissue distribution of PTX-loaded Pluronic P105 micellar system. The micelles were prepared by thin-film method using a nonionic surfactant Pluronic P105 and a hydrophobic anticancer drug, PTX. With a dynamic light scattering sizer and a transmission electron microscopy, it was shown that the PTX-loaded micelles had a mean size of approximately 24 nm with narrow size distribution and a spherical shape. The in vitro release profiles indicated that the release of PTX from the micelles exhibited a sustained release behavior. A similar phenomenon was also observed in a pharmacokinetic study in rats, in which t (1/2 beta) and AUC of the micelle formulation were 4.9 and 5.3-fold higher than that of Taxol injection. The biodistribution study in mice showed that the PTX-loaded micelles not only decreased drug uptake by liver, but also prolonged drug retention in blood and increased distribution of drug in lung, spleen and kidney. These results suggested that the P105 polymeric micelles may efficiently load, protect and retain PTX in both in vitro and in vivo environments, and could be a useful drug carrier for i.v. administration of PTX.


Alterations of T-lymphocyte populations in Parkinson disease.
Immune reaction-related inflammation may be important in the pathogenesis of Parkinson disease (PD). To elucidate peripheral immunologic alterations in PD, we characterized extended peripheral T-lymphocyte populations in 33 patients with PD and 34 normal subjects. Patients with PD had significantly decreased CD4+:CD8(+)T-cell ratios (P<0.001), fewer CD4(+)CD25(+)T cells (P<0.01), and significantly increased ratios of IFN-gamma-producing to IL-4-producing T cells (P<0.001). The characteristics of predominant expression of CD8(+)T cells, depletion of CD4(+)CD25(high) cells, and a shift to a T(H)1-type immune response in the peripheral immune system in PD patients may reflect an immune reaction-associated inflammatory process in the brain.


Mapping of enkephalin-related peptides in the nervous system of the blowfly, Calliphora vomitoria, and their co-localization with cholecystokinin (CCK)- and pancreatic polypeptide (PP)-like peptides.
The distribution of enkephalin-like immunoreactive material has been studied in the CNS of C. vomitoria. The presence of both Met- and Leu-enkephalin-related peptides is suggested by differential immunostaining with a variety of antisera. Comparisons made between certain of the enkephalin-immunoreactive perikarya, nerve fibres and terminals with cells in corresponding positions as evidenced in previously published neuroanatomical studies of the dipteran brain have suggested specific enkephalinergic pathways. As examples, one Met-enkephalin-immunoreactive neuron appears to link the lobula with the dorsal protocerebrum, and a group of Leu-enkephalin cells in the pars intercerebralis appear to have arborisations in both the central body (fan-shaped body) and the tritocerebral neuropil around the oesophageal foramen. Neuronal pathways of this type indicate that the enkephalin-like peptides of the fly brain are functioning as neurotransmitters and/or neuromodulators. In the thoracic ganglia, symmetrically arranged cells, immunoreactive to both Met- and Leu-enkephalin antisera, are positioned ventrally in pairs on either side of the mid-line in a sagittal plane. Very little immunoreactive material is observed in the neuropil, however, and the source of the accumulation of Leu-enkephalin-immunoreactivity in the dorsal neural sheath is not certain. It is suggested that this material, in contrast to that present in areas of the brain, acts as a neurohormone and that it may have a physiological role following its release into the haemolymph. The enkephalin-like immunoreactive material of certain neurons identified within the brain and thoracic ganglion shows a complex pattern of co-existence with pancreatic polypeptide- and gastrin/cholecystokinin-like peptides.


Cholesterol distribution between HDL subfractions. A study of 498 subjects.
In 498 subjects (205 normolipidemics and 293 hyperlipidemics) of both sexes, the cholesterol content of high density lipoprotein (HDL) subfractions has been determined. The serum concentration of total HDL-cholesterol appears to be more strictly related to the cholesterol content of HDL2 than to that of HDL3. This latter one, however, gives a contribution to the variability of HDL-cholesterol so that the value of HDL-cholesterol cannot be assumed as a reliable estimate of the serum level of the more anti-atherogenic HDL2 subfraction. The cholesterol content of HDL and its subfractions is higher in women than in men and decreases with increasing serum VLDL-cholesterol level and body weight. Both HDL2- and HDL3-cholesterol appear to largely depend from the metabolism of triglyceride-rich lipoproteins in accordance with the data of experimental studies.


A metalloprotease activity from C6 glioma cells inactivates the myelin-associated neurite growth inhibitors and can be neutralized by antibodies.
Glioblastoma cells infiltrate brain tissue and migrate preferentially along white matter fibre tracts, an environment that is highly inhibitory to the migration of astrocytes and the growth of neurites because of the presence of specific inhibitory proteins. In vitro, spreading and migration of rat C6 glioma cells on a CNS (central nervous system) myelin substrate is correlated with and dependent on the presence of a metalloprotease. This membrane-bound metalloendoprotease exhibits a blocker profile different from known proteases. Pretreatment of CNS myelin or of a highly purified CNS myelin component, the inhibitory protein bNI-220, with C6 metalloproteolytic activity converts these non-permissive substrates into permissive environments for astrocytes and fibroblasts, indicating that this C6 cell-derived metalloprotease may inactivate myelin-associated inhibitory proteins. Antibodies were raised in chicken against fractions enriched in metalloproteolytic activity; these antibodies were able to inhibit specifically spreading and migration of C6 glioma cells on a CNS myelin substrate, as well as the invasion of C6 cells into adult rat optic nerve explants in vitro. These results suggest a crucial involvement of a membrane-bound metalloprotease in the mechanisms of C6 glioma migration and infiltration of brain tissue by proteolytic inactivation of the neurite growth inhibitory proteins present in CNS myelin.


Self-reported oral and general health related to xerostomia, hyposalivation, and quality of life among caries active younger adults.
Objective: The aim was to study prevalence of xerostomia, hyposalivation and quality of life among caries active younger adults.Materials and methods: A questionnaire regarding oral and general health, xerostomia and quality of life was mailed to 134 caries active (CA) and 40 caries inactive (CI) patients, 25-50 years of age (mean age 39.9 ± 6.2 years) treated at a Swedish Public Dental Service clinic, regarding oral and general health, xerostomia and quality of life. Caries data and unstimulated whole salivary flow rates were obtained from dental records.Results: The overall response rate was 69%. Dental records confirmed that CA patients had more decayed teeth over time than CI patients (p < .001). The CA group reported worse oral health (p < .001) and general health (p < .01), more xerostomia (p < .001) and lower salivary flow rate (p < .01) compared to CI patients. Xerostomia was inversely related to unstimulated whole salivary flow rates as well as to oral and general health (p < .01). There were no differences between groups in quality of life.Conclusion: Younger caries active adult patients reported significantly more xerostomia and hyposalivation compared to caries inactive patients. Xerostomia and hyposalivation were inversely related to perceptions of oral and general health, but not to quality of life.


Natural cell-mediated cytotoxicity in vitiligo.
Natural cell-mediated cytotoxicity was studied in 18 patients with vitiligo and 13 healthy age-, race-, and sex-matched control subjects. The 4-hour chromium51 (51Cr) release assay was used to determine the activity of natural killer (NK) cells in the peripheral blood against K562 and Molt-4 target cells. Patients with vitiligo had a 50%, 67%, and 60% decrease in the cytotoxic response with Molt-4 cells at effector-target ratios of 25:1, 50:1, and 100:1, respectively, in comparison with control subjects (p less than 0.001). This inhibition was consistent with an 80% decrease in the binding capacity of NK cells to Molt-4 target cells (p less than 0.005). In contrast, cytotoxic responses did not differ in patients and control subjects with K562 target cells. These results suggest that patients with vitiligo have a decreased capacity for effector cell recognition of Molt-4 target cells but not K562 target cells. Hence patients with vitiligo may have defective clones of NK cells that are incapable of initial recognition of Molt-4 target cells, a necessary prerequisite for target cell lysis. Perhaps this phenomenon occurs with other tumor cells, which would explain the association of vitiligo with certain internal malignancies.


Effect of l-phenylalanine on PAL activity and production of naphthoquinone pigments in suspension cultures of Arnebia euchroma (Royle) Johnst.
The effects of l-phenylalanine (PHE) on cell growth and production of shikonin and its derivatives, acetylshikonin (ACS) and isobutyrylshikonin (IBS), in suspension cultures of Arnebia euchroma were examined. Supplementing media using PHE have been successfully utilized to enhance shikonin production in cell cultures of other species of Boraginaceae. l-Phenylalanine, the key compound in the phenylpropanoid pathway, is converted by phenylalanine ammonia lyase (PAL) to trans-cinnamic acid, which is the precursor of p-hydroxybenzoic acid (PHB). Coupling of PHB and geranyl pyrophosphate (derived from mevalonate pathway) by p-hydroxybenzoate-m-geranyltransferase leads later to biosynthesis of shikonins. The addition of 0.01 or 0.1 mM PHE to the culture medium stimulated cell proliferation, where the highest observed increase in fresh cell biomass (measured as a ratio of final weight to initial weight) was 12-fold, in contrast to an eightfold increase in control cultures. Whereas, growth media supplemented with 1 mM PHE markedly reduced the rate of cell growth (to only twofold). Precursor feeding had detrimental effects on both ACS and IBS production in all PHE-supplemented media. The highest total content (intracellular + extracellular) of the investigated red pigments (9.5 mg per flask) was detected in the control culture without PHE. ACS was the major component of the naphthoquinone fraction determined in cells and post-culture media. Shikonin itself was found only in the post-culture media from cultures supplemented with 0.01 or 0.1 mM PHE. Increases in PAL activity corresponded well with the accumulation of investigated naphthoquinones in control culture. However, peak PAL activity did not directly correlate with maximum production of shikonin derivatives. Cytotoxicity of extracts, prepared from the cells cultivated in the presence of PHE or in control cultures, was tested on three cancer cell lines: HL-60, HeLa, and MCF-7. The extracts prepared from the untreated control cultures proved to be the most potent against the examined cancer cell lines. The mean inhibitory concentration values were 0.3, 13, and 8 μg ml(-1) for the HL-60, HeLa, and MCF-7 cells, respectively.


Murine diet/tissue and human brain tumorigenesis alter Mthfr/MTHFR 5'-end methylation.
Polymorphisms and decreased activity of methylenetetrahydrofolate reductase (MTHFR) are linked to disease, including cancer. However, epigenetic regulation has not been thoroughly studied. Our goal was to generate DNA methylation profiles of murine/human MTHFR gene regions and examine methylation in brain and liver tumors. Pyrosequencing in four murine tissues revealed minimal DNA methylation in the CpG island. Higher methylation was seen in liver or intestine in the CpG island shore 5' to the upstream translational start site or in another region 3' to the downstream start site. In the latter region, there was negative correlation between expression and methylation. Three orthologous regions were investigated in human MTHFR, as well as a fourth region between the two translation start sites. We found significantly increased methylation in three regions (not the CpG island) in pediatric astrocytomas compared with control brain, with decreased expression in tumors. Methylation in hepatic carcinomas was also increased in the three regions compared with normal liver, but the difference was significant for only one CpG. This work, the first overview of the Mthfr/MTHFR epigenetic landscape, suggests regulation through methylation in some regions, demonstrates increased methylation/decreased expression in pediatric astrocytomas, and should serve as a resource for future epigenetic studies.


The concomitant expression and availability of conventional and alternative, cyanide-insensitive, respiratory pathways in Candida albicans.
The opportunistic oral pathogen Candida albicans expresses a cyanide-insensitive alternative oxidase (AOX) upon exposure to respiratory inhibitors that act downstream from coenzyme Q, and upon ageing of cells. To investigate whether the conventional pathway is retained when the alternative pathway is induced, cells were grown in the presence of sodium cyanide, a reversible inhibitor of cytochrome oxidase. AOX expression was monitored by Western blotting and the presence of cytochromes associated with complexes III and IV of the conventional pathway was monitored by recording spectra between 500 and 650 nm at 77K. The activities of complexes III and IV were determined in polarographic and enzyme-kinetic experiments using specific respiratory substrates and inhibitors. Results indicated that complexes III and IV are constitutively expressed and are functional in cells expressing AOX. Furthermore, the enzymatic activities of complexes III and IV were similar in mitochondrial preparations from cells grown with or without cyanide. We next investigated whether both pathways are simultaneously available for electron transfer from the Q pool to molecular oxygen. Respiration was virtually completely inhibited by the combination of cyanide and salicyl hydroxamic acid (SHAM) or antimycin A and SHAM, but only partly inhibited by either of these inhibitors alone. This indicates that electrons can in principle flow either through the conventional or the alternative respiratory pathway. The availability of two electron pathways in C. albicans and the potential use of either pathway endows this pleomorphic fungus with another level at which it can rapidly adjust to altered environmental conditions.


Turnover of phospholipid linoleic and arachidonic acids in human platelets from plasma lecithins.
Incubation of platelet-rich plasma with high density lipoproteins labeled either with 1-acyl-2[1-14c]-arachidonoyl-sn-glycero-3-phosphocholine or 1-acyl-2-[1-14c]linoleoyl-sn-glycero-3-phosphocholine showed the existence of a pool of phosphatidylcholine in platelets, which rapidly exchanges with the phosphatidylcholine in plasma. The labeled linoleic and arachidonic acids from the respective labeled phosphatidylcholines were found in the other glycerophospholipids. These transacylation processes were much more active with the arachidonoyl-labeled phosphatidylcholine than with linoleoyl-labeled phosphatidylcholine. Arachidonic acid was mainly found in the phosphatidylinositol.


Heterologous expression of functionally active enterolysin A, class III bacteriocin from Enterococcus faecalis, in Escherichia coli.
The heterologous expression of enterolysin A (EnlA), heat-labile class III bacteriocin from Enterococcus faecalis II/1 with anti-listerial activity, was studied in Escherichia coli. The PCR amplified products of enterolysin A structural gene, N-terminal part of EnlA with endopeptidase-like activity and C-terminal part of EnlA similar to a lysis gene of bacteriophage, were cloned in prelinearized pQE-30UA expression vector. The expression of EnlA structural gene led to the synthesis and secretion of functional-active His-tagged enterolysin A protein, which was purified to homogeneity using His-Select Cartridge and was shown to be fully active against the indicator strain. The expression of N-terminal or C-terminal part of EnlA and deletion of last 58 amino acids from C-terminal domain of EnlA led to the synthesis of biologically non-active proteins.


The syndrome of facial nevi, anomalous cerebral venous return, and hydrocephalus.
A 25-year-old man with facial and nuchal pigmentation and contrast radiographic changes identical to those in the syndrome described by Shapiro and Shulman is reported. Without surgical intervention in infancy, the patient attained normal maturation and development.


Suicidality in patients with primary diagnosis of panic disorder: A single-rate meta-analysis and systematic review.
This study investigated the lifetime suicide attempt and ideation rates among patients with panic disorder (PD). Online databases regarding lifetime suicide attempt and ideation rates in patients with PD were searched up to May 2021. The suicide attempt and ideation rates were 0.17 (95% CI: 0.16, 0.18) and 0.23 (95% CI: 0.22, 0.25). The suicide attempt rates among female and male patients were 0.17 (95% CI: 0.14, 0.20) and 0.15 (95% CI: 0.12, 0.19). When PD was comorbid with anxiety, depression, substance abuse, and personality disorders, the suicide attempt rates increased to 0.23 (95% CI: 0.20, 0.26), 0.23 (95% CI: 0.18, 0.27), 0.25 (95% CI: 0.20, 0.31), and 0.25 (95% CI: 0.23, 0.28), respectively. The suicide attempt and ideation by age, suicide ideation by sex, and suicide ideation by comorbidity with other mental disorders were passed in our meta-analysis as sample size was small. Stratification analysis on ethnicity, marital status, education levels, resident location, and severity of PD should be considered in the future. The lifetime suicide ideation and attempt rates in patients with PD were higher than general populations but lower than patients with bipolar or depression. The lifetime suicide attempt rate in female patients was slightly higher than male patients. When PD was comorbid with one other mental illness, the lifetime suicide attempt rate increased by about 50%.


Influence of vegetation and substrate on the removal and transformation of dissolved organic matter in horizontal subsurface-flow constructed wetlands.
The fate of dissolved organic matter (DOM) during horizontal subsurface-flow constructed wetlands (HSSF CWs) was examined. In several studies it had been demonstrated that factors such as vegetation and substrates type affected the treatment efficiency of DOM, while very few studies discerned their influence on the transformations of DOM. Thus three pilot-scale HSSF CWs, i.e. reed (Phragmites australis)/gravel bed (W1), hybrid vegetation{cattail (Typha latifolia), bulrush (Scirpus validus), reed}/gravel bed (W2) and reed/hybrid substrates bed (gravel, zeolite, slag) (W3), were designed, and were operated continuously to investigate soluble COD (SCOD) removal and DOM transformations affected by vegetation and substrate type, and to explore the correlation between SCOD and biodiversity. The results showed that cattail and bulrush contributed to higher SCOD removal than common reed, and that gravel, zeolite and slag did not show significant influence on SCOD removal. The composition of the dissolved organic carbon (DOC) could undergo a considerable shift in composition due to metabolism and senescence from plant and microorganism. Nonlabile aromatic hydrocarbons and alkyl hydrocarbons in the effluent were a significant portion compared with labile alcoholic and alkene in the influent. It was also observed that the type of vegetation and substrate had great influence on the structure of bacteria, and the Shannon-Wiener Index increased linearly with the decrease of SCOD concentration along water flow in W2 and W3 (R2=0.96).


Urinary striated sphincter: what is its nerve supply?
Innervation of the voluntary urinary sphincter continues to be a controversial subject. Using retrograde axonal transport techniques to determine the exact nerve supply to the external sphincter has been successful in clarifying this controversy. 1-5 Tracing the transport of horseradish peroxidase (HRP) injected in the voluntary external sphincter and that injected directly in the cut end of the pudendal nerve was done. Transport from both sides ended in the same neurons in the dorsolateral column, thus labelling and identifying the pudendal nucleus which is the motor center for the voluntary urinary sphincter.


Prehospital administration of broad-spectrum antibiotics for sepsis patients: A systematic review and meta-analysis.
Some studies have suggested that earlier initiation of antibiotics has shown positive outcomes in sepsis patients. We aimed to do a systematic review and meta-analysis to evaluate the effect of prehospital administration of antibiotics on 28 days mortality and length of stay in hospital and intensive care unit for sepsis patients. We formulated a search strategy and used it on search databases PubMed, Scopus, Web of Science, and Embase. We then screened the records for eligibility and included controlled studies, either clinical trials or cohort studies reporting prehospital antibiotic administration for sepsis patients. We excluded duplicates, books, conferences' abstracts, case reports, editorials, letters, author responses, not English studies, and studies with nonavailable full text. Animal and lab studies were also excluded. The total number of studies identified is 1811, 19 were eligible for systematic review and 4 for meta-analysis (three cohort and one clinical trial). The total number of sepsis patients in the four included studies in the 28 days mortality outcome was 3523 (1779 took prehospital antibiotics and 1744 did not take prehospital antibiotics). Of 1779 who took the antibiotics, 190 died, and of 1744 who did not take antibiotics, 292 died (95% confidence interval 0.68-0.97, p = 0.02). This meta-analysis reveals that receiving prehospital antibiotics can significantly lower mortality in sepsis patients compared to patients who do not receive prehospital antibiotics. However, more clinical trials and multicenter prospective studies with high sample sizes are needed to get strong evidence supporting our findings.


Jaw bone marrow-derived osteoclast precursors internalize more bisphosphonate than long-bone marrow precursors.
Bisphosphonates (BPs) are widely used in the treatment of several bone diseases, such as osteoporosis and cancers that have metastasized to bone, by virtue of their ability to inhibit osteoclastic bone resorption. Previously, it was shown that osteoclasts present at different bone sites have different characteristics. We hypothesized that BPs could have distinct effects on different populations of osteoclasts and their precursors, for example as a result of a different capacity to endocytose the drugs. To investigate this, bone marrow cells were isolated from jaw and long bone from mice and the cells were primed to differentiate into osteoclasts with the cytokines M-CSF and RANKL. Before fusion occurred, cells were incubated with fluorescein-risedronate (FAM-RIS) for 4 or 24h and uptake was determined by flow cytometry. We found that cultures obtained from the jaw internalized 1.7 to 2.5 times more FAM-RIS than long-bone cultures, both after 4 and 24h, and accordingly jaw osteoclasts were more susceptible to inhibition of prenylation of Rap1a after treatment with BPs for 24h. Surprisingly, differences in BP uptake did not differentially affect osteoclastogenesis. This suggests that jaw osteoclast precursors are less sensitive to bisphosphonates after internalization. This was supported by the finding that gene expression of the anti-apoptotic genes Bcl-2 and Bcl-xL was higher in jaw cells than long bone cells, suggesting that the jaw cells might be more resistant to BP-induced apoptosis. Our findings suggest that bisphosphonates have distinct effects on both populations of osteoclast precursors and support previous findings that osteoclasts and precursors are bone-site specific. This study may help to provide more insights into bone-site-specific responses to bisphosphonates.


Case 9: heavily exuding, malodorous, necrotic pressure ulcer.
In this case, the necrotic tissue was so hard it was not possible to categorise the ulcer. Octenilin products were able to debride the necrotic tissue, so that the wound depth could be determined. After 4 weeks, the wound was covered with granulation tissue, improving the patient's quality of life.


Molecular investigation of TSHR gene in Bangladeshi congenital hypothyroid patients.
The disorder of thyroid gland development or thyroid dysgenesis accounts for 80-85% of congenital hypothyroidism (CH) cases. Mutations in the TSHR gene are mostly associated with thyroid dysgenesis, and prevent or disrupt normal development of the gland. There is limited data available on the genetic spectrum of congenital hypothyroid children in Bangladesh. Thus, an understanding of the molecular aetiology of thyroid dysgenesis is a prerequisite. The aim of the study was to investigate the effect of mutations in the TSHR gene on the small molecule thyrogenic drug-binding site of the protein. We identified two nonsynonymous mutations (p.Ser508Leu, p.Glu727Asp) in the exon 10 of the TSHR gene in 21 patients with dysgenesis by sequencing-based analysis. Later, the TSHR368-764 protein was modeled by the I-TASSER server for wild-type and mutant structures. The model proteins were targeted by thyrogenic drugs, MS437 and MS438 to perceive the effect of mutations. The damaging effect in drug-protein complexes of mutants was explored by molecular docking and molecular dynamics simulations. The binding affinity of wild-type protein was much higher than the mutant cases for both of the drug ligands (MS437 and MS438). Molecular dynamics simulates the dynamic behavior of wild-type and mutant complexes. MS437-TSHR368-764MT2 and MS438-TSHR368-764MT1 showed stable conformations in biological environments. Finally, Principle Component Analysis revealed structural and energy profile discrepancies. TSHR368-764MT1 exhibited much more variations than TSHR368-764WT and TSHR368-764MT2, emphasizing a more damaging pattern in TSHR368-764MT1. This genetic study might be helpful to explore the mutational impact on drug binding sites of TSHR protein which is important for future drug design and selection for the treatment of congenital hypothyroid children with dysgenesis.


Actin filaments in the terminal webs of secretory ameloblasts of rats.
Actin filaments decorated with heavy meromyosin in enamel-secreting ameloblasts of rat incisors were examined. Proximal and distal terminal webs contained actin filaments; some were arrayed in diverse directions to each other. Some were associated with coated and uncoated vesicles. These actin filaments may relate to the sideways movement of secreting ameloblasts, suggesting that the distal terminal web is an apparatus generating a force by which ameloblasts can slide over each other.


Hydroxychloroquine for treatment of nonsevere COVID-19 patients: Systematic review and meta-analysis of controlled clinical trials.
Being a pandemic and having a high global case fatality rate directed us to assess the evidence strength of hydroxychloroquine efficacy in treating coronavirus disease-2019 (COVID-19) arising from clinical trials and to update the practice with the most reliable clinical evidence. A comprehensive search was started in June up to 18 July, 2020 in many databases, including PubMed, Embase, and others. Of 432 studies found, only six studies fulfilled the inclusion criteria, which includes: clinical trials, age more than 12 years with nonsevere COVID-19, polymerase chain reaction-confirmed COVID-19, hydroxychloroquine is the intervention beyond the usual care. Data extraction and bias risk assessment were done by two independent authors. Both fixed-effect and random-effect models were utilized for pooling data using risk difference as a summary measure. The primary outcomes are clinical and radiological COVID-19 progression, severe acute respiratory syndrome coronavirus-2 clearance in the pharyngeal swab, and mortality. The secondary outcomes are the adverse effects of hydroxychloroquine. Among 609 COVID-19 confirmed patients obtained from pooling six studies, 294 patients received hydroxychloroquine and 315 patients served as a control. Hydroxychloroquine significantly prevents early radiological progression relative to control with risk difference and 95% confidence interval of -0.2 (-0.36 to -0.03). On the other hand, hydroxychloroquine did not prevent clinical COVID-19 progression, reduce 5-day mortality, or enhance viral clearance on days 5, 6, and 7. Moreover, many adverse effects were reported with hydroxychloroquine therapy. Failure of hydroxychloroquine to show viral clearance or clinical benefits with additional adverse effects outweigh its protective effect from radiological progression in nonsevere COVID-19 patients. Benefit-risk balance should determine the hydroxychloroquine use in COVID-19.


Reasons for and costs of hospitalization for pediatric asthma: a prospective 1-year follow-up in a population-based setting.
The aims of this study were to examine the frequency of, and the reasons for, emergency hospitalization for asthma among children. In addition, the costs of hospital treatment, preventive medication, and productivity losses of the caregivers were evaluated in a population-based setting during 1 year. Data on purchases of regular asthma medication were obtained from the Social Insurance Institution. In total, 106 (2.3/1000) children aged up to 15 years were admitted 136 times for asthma exacerbation to the Kuopio University Hospital in 1998. This represented approximately 5% of all children with asthma in the area. The trigger for the exacerbation was respiratory infection in 63% of the episodes, allergen exposure in 24%, and unknown in 13%. The age-adjusted risk for admittance was 5.3% in children on inhaled steroids, 5.8% in those on cromones, and 7.9% in those with no regular medication for asthma. The mean direct cost for an admission was $1,209 (median $908; range $454-6,812) and the indirect cost was $358 ($316; $253-1,139). The cost of regular medication for asthma was, on average, $272 per admitted child on maintenance. The annual total cost as a result of asthma rose eight-fold if a child on regular medication was admitted for asthma.


In vivo and in vitro production options for fungal secondary metabolites.
Microbial natural products, among them a vast diversity of fungal origin, represent a major source for new drug candidates. Focusing on fungal metabolites, our review covers recent advances in the field of biotransformation, heterologous expression, in vivo production approaches, genomics, and the metabolism of unexplored fungal groups as options to generate and identify new compounds or optimize known ones.


Purification and properties of glutamate binding protein from the periplasmic space of Escherichia coli K-12.
Glutamate binding protein released from the periplasmic space of Escherichia coli K-12 by lysozyme-EDTA treatment was purified to homogeneity and its physical and chemical properties were studied. It is a basic protein with a pI of 9.1. Its molecular weight, determined in an analytical ultracentrifuge, and by gel filtration on Sephadex G-100 and dodecylsulphate acrylamide is 29 700, 27 800 and 32 000, respectively. The KD value for glutamate was 6.7 - 10- minus 6 M. L-Aspartate, reduced glutathione, G-glutamate-gamma-benzylester and L-glutamate-gamma-ethylester competitively inhibited glutamate binding with K-i; values of 7.8 - 10- minus 5, 1.1 - 10- minus 5, 1.0 - 10- minus 5 and 1.0 - 10- minus 5 M, respectively. Spheroplasts retained 40% of glutamate transport as compared to intact cells. The glutamate binding activity of a glutamate-utilizing strain (CS7), was 1.6 times as high as that of the glutamate non-utilizing parent strain (CS101). Similarly, the glutamate binding activity of a temperature conditional glutamate-utilizing mutant (CS2-TC) was 1.9 times higher when grown at the permissive temperature (42 degrees C) than when grown at the restrictive temperature (30 degrees C).


Stability in an annually defaunated estuarine soft-bottom community.
The concept of biological stability is so complex that at least six different meanings have been ascribed to it. We propose that one definition, "the ability of a system once perturbed to return to its previous state" be utilized as a working definition. Using quantitative data collected monthly from a soft-bottom community that undergoes an annual natural catastrophic defaunation coupled with a recently developed analytical technique, we demonstrate the feasability of a working definition and show the existence of stability in the soft-bottom community. The utility of a working definition of stability in the evaluation of disturbance is discussed.


Effects of nonenzymatic glycosylation of extracellular matrix components on cell survival and sensory neurite extension in cell culture.
Diabetic sensory polyneuropathy is characterized by a distal axonopathy of dying-back type. It is accompanied by a failure of axonal regeneration, in which nonenzymatic glycosylation (glycation) of the extracellular matrix may be involved. In the present study, the effects of glycation of collagen IV and laminin, major components of basal lamina, on neuron survival and neurite extension were investigated in tissue culture. Fast glycation of laminin was achieved by incubation with glycolaldehyde and glycation of collagen IV by incubation with glucose. The degree of glycation was estimated by fluorescence analysis. Glycated or nonglycated laminin or collagen IV were used as substrates for culture of dorsal root ganglion (DRG) neurons from neonatal rats. Cultures were assessed for the proportion of cells attaching to the substrate, surviving and bearing neurites. Cell attachment and the proportion bearing neurites were significantly reduced on collagen IV glycated for 2 weeks, but survival was only affected by glycation for 4 or 5 weeks. All 3 parameters were significantly reduced on glycated compared with unglycated laminin. Glycation of both laminin and collagen IV produced considerable morphological differences in the cultured neurons on scanning electron microscopy. Dissociated DRG neurons from adult animals with streptozotocin-induced diabetes cultured on nonglycated substrates survived less well and produced fewer neurites. Glycation of collagen IV and laminin thus affects neuronal survival, neurite production and cell morphology, and diabetes affects both the survival of sensory neurons in culture and their ability to extend neurites.


Ionic channels in cultured Drosophila neurons.
Cultured "giant" Drosophila neurons derived from cytokinesis-arrested embryonic neuroblasts express various membrane channels and excitability patterns. Both current- and voltage-clamp recordings could be performed on the same neuron owing to the large cell size, thus making it possible to elucidate the functional role of individual types of channels. This culture system has been used to analyze the mutational perturbations in ion channels and the resultant alterations in membrane excitability.


Visible-Light Photoswitching by Azobenzazoles.
Three visible-light responsive photoswitches are reported, azobis(1-methyl-benzimidazole) (1), azobis(benzoxazole) (2) and azobis(benzothiazole) (3). Photostationary distributions are obtained upon irradiation with visible light comprising approximately 80 % of the thermally unstable isomer, with thermal half-lives up to 8 min and are mostly invariant to solvent. On protonation, compound 1H+ has absorption extending beyond 600 nm, allowing switching with yellow light, and a thermal half-life just under 5 minutes. The two isomers have significantly different pKa values, offering potential as a pH switch. The absorption spectra of 2 and 3 are insensitive to acid, although changes in the thermal half-life of 3 indicate more basic intermediates that significantly influence the thermal barrier to isomerization. These findings are supported by high-level ab initio calculations, which validate that protonation occurs on the ring nitrogen and that the Z isomer is more basic in all cases.


Progranulin correlated with rapid progressive interstitial lung disease in dermatomyositis with anti-melanoma differentiation-associated gene 5 antibody.
This study aimed to detect the expression of progranulin (PGRN) and elucidate associations with clinical features in dermatomyositis (DM) patients with anti-melanoma differentiation-associated gene 5 (anti-MDA5) antibody. We enrolled 40 DM patients with anti-MDA5 antibody, 20 patients with antisynthetase syndrome (ASS; disease control), and 20 healthy individuals (healthy control, HC). The clinical features of patients with anti-MDA5 antibody and anti-histidyl-tRNA antibody were collected. The level of PGRN in the serum was tested by ELISA. The PGRN levels in DM patients with anti-MDA5 antibody (166.74 ± 97.95 ng/ml) were significantly higher than those in patients with ASS (82.66 ± 40.50 ng/ml; p < 0.001) and in HC (42.34 ± 18.69 ng/ml; p < 0.001). Patients with rapid progressive interstitial lung disease (RP-ILD) in DM with anti-MDA5 antibody (213.57 ± 114.05 ng/ml) had higher levels of PGRN than those without RP-ILD (135.51 ± 72.41 ng/ml; p = 0.012). ROC analysis showed an AUC value at 0.715 (95% CI, 0.541-0.888) for diagnosis of RP-ILD in DM patients with anti-MDA5 antibody. The expression of PGRN was positively correlated with the levels of ALT, AST, CK, LDH and ferritin (all p < 0.05). Our results indicated PGRN had great potential as a valuable serum marker of RP-ILD in DM with anti-MDA5 antibody. Key Points The level of PGRN was elevated in DM patients with anti-MDA5 antibody, especially for those with RP-ILD.


Opioid analgetics retention-pharmacologic activity models using biopartitioning micellar chromatography.
Opioids are drugs used in medicine for pain control. In this paper, retention-pharmacokinetics and retention-pharmacodynamics relationships of opioids are proposed and statistically validated. These models are based on the compound retention in the biopartitioning micellar chromatography system (BMC), a new methodology which has successfully been used to develop QRAR models for many other families of compounds. The obtained results are compared to the traditional QSAR models using lipophilicity data. The adequacy of QRAR models is due to the fact that the characteristics of the compounds such as the hydrophobicity, electronic charge and steric effects determine both their retention in BMC and their pharmacokinetic and pharmacodynamic behavior.


Employing the immunological synapse in AML: development of leukemic dendritic cells for active specific immunization.
Cytotoxic T cells directed against leukemic blasts have been observed in patients with acute myeloid leukemia (AML). However, generation of efficient T-cell responses is hampered due to several factors that enable AML blasts to protect themselves from the patients immune system. Improved immune responses can be established by the differentiation of AML blasts into AML-derived dendritic cells (DC) thereby conserving their intrinsic leukemia specific antigens and obtaining full capacity to present these antigens to naive T cells. This review discusses increased immunogenicity of AML blasts by differentiation into AML-DC and describes ways to augment the AML-DC vaccination approach.


Demonstration of static electricity induced luminescence.
Can we visualise static electricity, which everyone in the world knows about? Since static electricity is generated by contact or peeling, it may be a source of malfunction of electronic components, whose importance is steadily increasing, and even cause explosion and fire. As static electricity is invisible, makeshift measures of static electricity are taken on various surfaces; there is also a common view that it is hard to take effective measures. Here we present a specific luminescent material, SrAl2O4: Eu2+, which emits light at excitation by an electrostatic charge in the air. Till now, in the interaction between electricity and luminescent materials, it was considered that emission of light is enabled by accelerated particles colliding with the luminescent material in vacuo. There have been no reports on luminescent materials being responsive to low-energy electrostatic charges under atmospheric pressure. Using SrAl2O4: Eu2+ luminescent material discovered by us, we succeeded for the first time in static electricity visualisation in the form of green light. In addition to the fact that such static electricity induced luminescence assists in solving electrostatic-related problems in the industry, it also provides a new measurement method that facilitates the observation of previously invisible electric charges in the air.


[Immunity of middle age and aged patients with tuberculosis and its changes during multimodality treatment by using T-activin].
Fifty six patients with pulmonary tuberculosis were examined. Of them 30 had T-activin in multimodality treatment. To supplement the agent in elderly and old patients was found to elevate the counts of T lymphocytes and T helper cells, to normalize Tx/Tc ratios, to enhance T lymphocytic activity and IL-2 synthesis. At the same time there was an increase in nonspecific responsiveness: enhancement of NKC activity and IL-1 synthesis by macrophages. With this, stimulation of specific antituberculous immunity took place. Normalization of immunological responsiveness and stimulation of specific antituberculous immunity were associated with enhanced therapeutical efficiency.


Postmortem changes in stereological parameters of cerebral capillaries.
The present study investigated the influence of different postmortem times on stereological parameters of capillaries in the cerebral cortex. For the human investigation different brain regions of two 77 and 79 year-old subjects were examined. The animal experiment, carried out on 10 male cats, allowed a comparison between intravitam deep-frozen cerebral cortex and tissue obtained after decapitation. The parameters were diameter Di, volume fraction VVi, surface-to-volume ratio Si/Vi, mean minimal distance between capillary centers of gravity deltaAB, length per unit cortex volume LVi, and number of fragments per measuring field Ni, AT. Neither the cat experiment nor the human investigation yielded a noteworthy change of the capillary diameter in the postmortem cortical tissue. Nevertheless, a significantly enlarged mean minimal distance between capillaries in the cat cerebral cortex shortly after decapitation (30 sec) suggests the formation of edema which then regresses. Furthermore the experiment revealed that 22 hours after death there is a significantly (p less than 0.01) diminished volume fraction and length per unit cortex volume with an augmented surface-to-volume ratio. These changes are thought to be a consequence of water loss. In contrast to the animal experiment the human cerebral capillaries showed no changes in stereological parameters at two different postmortem times. These results encourage continuation of further stereological investigations on human brains obtained at autopsy and may contribute to the understanding of the aging process in the human cerebral cortex.


Identification of a novel ene reductase from Pichia angusta with potential application in (R)-levodione production.
Asymmetric reduction of electronically activated alkenes by ene reductases (ERs) is an attractive approach for the production of enantiopure chiral products. Herein, a novel FMN-binding ene reductase (PaER) from Pichia angusta was heterologously expressed in Escherichia coli BL21(DE3), and the recombinant enzyme was characterized for its biocatalytic properties. PaER displayed optimal activity at 40 °C and pH 7.5, respectively. The purified enzyme was quite stable below 30 °C over a broad pH range of 5.0-10.0. PaER was identified to have a good ability to reduce the C[double bond, length as m-dash]C bond of various α,β-unsaturated compounds in the presence of NADPH. In addition, PaER exhibited a high reduction rate (k cat = 3.57 s-1) and an excellent stereoselectivity (>99%) for ketoisophorone. Engineered E. coli cells harboring PaER and glucose dehydrogenase (for cofactor regeneration) were employed as biocatalysts for the asymmetric reduction of ketoisophorone. As a result, up to 1000 mM ketoisophorone was completely and enantioselectively converted to (R)-levodione with a >99% ee value in a space-time yield of 460.7 g L-1 d-1. This study provides a great potential biocatalyst for practical synthesis of (R)-levodione.


A novel electrochemical immunosensor based on magnetosomes for detection of staphylococcal enterotoxin B in milk.
In this paper, a novel electrochemical immunosensor to detect staphylococcal enterotoxin B based on bio-magnetosomes, polyaniline nano-gold composite and 1,2-dimethyl-3-butylimidazolium hexafluorophosphate ionic liquid, was developed, and found to exhibit high sensitivity and stability. The specific antibody to staphylococcal enterotoxin B conjugated with the magnetosomes showed rapid immunoreactions and good dispersion, which contributed to the formation of a nanostructurally smooth and dense film on the surface of a gold electrode. Polyaniline nano-gold composite and 1,2-dimethyl-3-butylimidazolium hexafluorophosphate ionic liquid were used to modify the electrode as mediators to improve the electron transfer and offer an excellent biocompatible microenvironment for the antibody to retain its activity to enhance the response of the electrochemical sensor. Under optimal conditions, the developed immunosensor showed a good linear response in the range from 0.05 to 5 ng/mL (R(2)=0.9957) with a detection limit as low as 0.017 ng/mL, compared with the one without magnetosomes (0.05-5 ng/mL, 0.033 ng/mL), this developed immunosensor showed a wider response range and a reduced detection limit. And a good specificity with little adsorption to staphylococcal enterotoxin A, C and Na(+), K(+), Ca(2+) was obtained. Moreover, the immunosensor exhibited a good long-time stability at 4 °C reaching up to 60 days, which showed a relatively long working life. Meanwhile the immunosensor could be regenerated four times using NaOH elution. The sensor also displayed a good repeatability with a relative standard deviation of 5.02% for staphylococcal enterotoxin B detection (1 ng/mL, n=9). Furthermore, high recoveries in milk samples from 81% to 118% were achieved and successfully applied to milk sample detection. The obtained results demonstrate that the developed electrochemical immunosensor is a promising tool for the detection of staphylococcal enterotoxin B in food.


[Electroresection of prostatic adenomas in patients with a high degree of surgical risk].
On the basis of an analysis of the operative treatment of 56 patients with prostate adenoma with a high degree of operative risk the authors recommend to fulfil a subtotal transurethral furrow electroresection of the adenoma. There was one lethal outcome after the operation.


Multi-Focus Beamforming for Thermal Strain Imaging Using a Single Ultrasound Linear Array Transducer.
Ultrasound-induced thermal strain imaging (TSI) has been used successfully to identify lipid- and water-based tissues in atherosclerotic plaques in some research settings. However, TSI faces several challenges to be realized in clinics. These challenges include motion artifacts and displacement tracking accuracy, as well as limited heating capability, which contributes to low thermal strain signal-to-noise ratio, and a limited field of view. Our goal was to address the challenge in heating tissue in TSI. Current TSI systems use separate heating and imaging transducers, which require physical alignment of the heating and imaging beams and result in a bulky setup that limits in vivo operation. We evaluated a new design for heating beams that can be implemented on a linear array imaging transducer and can provide improved heating area and efficiency as compared with previous implementations. The heating beams designed were implemented with a clinical linear array imaging transducer connected to a research ultrasound platform. In vitro experiments using tissue-mimicking phantoms with no blood flow revealed that the new design resulted in an effective heating area of approximately 0.85 cm2 and a 0.3°C temperature rise in 2 s of heating, which compared well with in silico finite-element simulations. With the new heating beams, TSI was found to be able to detect a lipid-mimicking rubber inclusion with a diameter of 1 cm from the water-based gelatin background, with a strain contrast of 2.3 (+0.14% strain in the rubber inclusion and -0.06% strain in the gelatin background). Lastly, lipid-based tissue in a 1-cm-diameter human carotid endarterectomy (CEA) sample was identified in good agreement with histology.


Fabrication of vascular endothelial growth factor antibody bioconjugated ultrasmall near-infrared fluorescent Ag2S quantum dots for targeted cancer imaging in vivo.
BSA-stabilized Ag2S QDs were fabricated in aqueous solution via a one-pot approach, and subsequently bioconjugated with antiVEGF for targeted in vivo cancer imaging.


Enhanced decontamination of levofloxacin as toxic pharmaceutical residuals from water using CaO/MgO nanorods as a promising adsorbent.
Novel MgO/CaO nanocomposite (MgO/CaO NRs) was synthesized by the hydrothermal method using diatomite porous frustules as a substrate under the microwave irradiation. The composite appeared as well crystalline rod-like nanoparticles with 52.3 nm as average particle size and 112.8 m2/g as BET surface area. The synthetic MgO/CaO NRs were addressed as a novel adsorbent for promising removal of levofloxacin (LVX) as pharmaceutical residuals. The adsorption studies revealed effective uptake of levofloxacin by MgO/CaO NRs with theoretical qmax of 106.7 mg/g and the equilibrium time of 720 min considering the best pH value (pH 7). The equilibrium studies highly fitted with the Langmuir model of monolayer adsorption considering the values of Chi-squared (χ2) and determination coefficient. The estimated adsorption energy from Dubinin-Radushkevich (0.2 kJ/mol) signifies physisorption mechanisms that might be coulombic attractive forces considering the kinetic studies. The thermodynamic addressing for the reactions verified their spontaneous and exothermic nature within a temperature range from 303 to 333 K. Additionally, the prepared MgO/CaO NRs show significant recyclability properties to be used in realistic remediation process and its uptake capacity is higher than several studied adsorbents in literature.


Biosynthesis and Characterization of a Novel Fibrinolytic Alkaline Serine Protease from Newly Isolated Bacillus flexus BF12 for Biomedical Applications.
Cardiovascular Diseases (CVDs) such as stroke, high blood pressure, peripheral vascular disease, ischemic heart disease and acute myocardial infarction are some of the leading causes of death. To treat CVDs, commercially available thrombolytic agents are widely used. However, these thrombolytic agents have various side effects. Alternatively, fibrinolytic enzymes from bacterial sources are highly safe and have direct blood clot lytic activity. A fibrinolytic enzyme producing bacterial strain, Bacillus flexus BF12, was isolated from a solar saltpan in Kanyakumari District, Tamilnadu, India. Enzyme production was improved by optimizing physical factors and nutritional factors. A novel fibrinolytic enzyme was isolated from a strain of the studied B. flexus BF12. Enzyme production was enhanced significantly by optimizing process parameters. The critical physical factors (pH and salinity) and influencing nutritional factors (carbon, nitrogen and ions) were optimized by one variable at a time approach, followed by the statistical method. The strain BF12 was highly active at alkaline pH (>7.0) and between 4 and 6% NaCl concentration. The nutrients such as fructose (carbon source), beef extract (nitrogen source) and CaCl2 significantly influenced enzyme production. Central composite design and response surface methodology improved 3.2-fold enzyme yield than unoptimized culture medium. Fibrinolytic protease was purified by ammonium sulphate precipitation, dialysis and gel filtration chromatography. The molecular weight of an enzyme was found to be 23 kDa. It was active at a broad temperature (40-60 °C) and pH (7.0-9.0) ranges. Enzyme activity was enhanced by Ca2+ and Co2+ ions. The purified protease retained 100% enzyme activity in the presence of ethanol and acetone. Acetonitrile, butanol, DMSO, methanol and chloroform showed enzyme activity of 63%, 92.5%, 94.7%, 92.3% and 90.4%, respectively. The purified enzyme degraded 100% of human blood clot. The Bacillus flexus BF12 fibrinolytic enzyme shows promising potentials in nutraceutical and food fortification applications. The application of fibrinolytic enzymes could prevent CVDs.


Identification of a new type of mammalian myosin heavy chain by molecular cloning. Overlap of its mRNA with preprotachykinin B mRNA.
In this paper, we report the polypeptide sequence, the mRNA sequence, and gene organization of a new category of mammalian myosin heavy chain, termed myosin I heavy chain-like protein (MIHC), on the basis of sequence analyses of cDNA clones isolated from a bovine intestinal cDNA library and a genomic DNA clone containing the MIHC gene. The MIHC mRNA shares its 3' sequence with the 5' sequence of the preprotachykinin B mRNA encoding the precursor for the neuromedin K neuropeptide. An overlap of these functionally unrelated mRNAs results from overlapping transcription of the same strand of the genomic DNA sequence. The deduced amino acid sequence comprising the amino-terminal two-thirds of the 119-kDa MIHC polypeptide is highly homologous to that portion of conventional myosin heavy chains which forms the globular head domain. The homology is particularly strong in the regions of sequence thought to be involved in forming the nucleotide- and actin-binding sites. By contrast, the deduced sequence comprising the carboxyl-terminal one-third of MIHC shows no significant homology to that portion of conventional myosin heavy chains which forms the alpha-helical coiled-coil rod-like tail. In this regard, MIHC more closely resembles the monomolecular, non-filamentous, low molecular weight myosin I heavy chain from Acanthamoeba castellanii. Furthermore, the size of the MIHC polypeptide, together with its preferential expression in intestinal tissue, leads us to speculate that MIHC and the 110-kDa intestinal brush-border protein (Collins, J. H., and Borysenko, C. W. (1984) J. Biol. Chem. 259, 14128-14135), which binds actin and has myosin-like ATPase activity, are the same or closely related proteins.


A soft, transparent, freely accessible cranial window for chronic imaging and electrophysiology.
Chronic in vivo imaging and electrophysiology are important for better understanding of neural functions and circuits. We introduce the new cranial window using soft, penetrable, elastic, and transparent, silicone-based polydimethylsiloxane (PDMS) as a substitute for the skull and dura in both rats and mice. The PDMS can be readily tailored to any size and shape to cover large brain area. Clear and healthy cortical vasculatures were observed up to 15 weeks post-implantation. Real-time hemodynamic responses were successfully monitored during sensory stimulation. Furthermore, the PDMS window allowed for easy insertion of microelectrodes and micropipettes into the cortical tissue for electrophysiological recording and chemical injection at any location without causing any fluid leakage. Longitudinal two-photon microscopic imaging of Cx3Cr1(+/- GFP) transgenic mice was comparable with imaging via a conventional glass-type cranial window, even immediately following direct intracortical injection. This cranial window will facilitate direct probing and mapping for long-term brain studies.


Cutaneous respiration in seven sea-water teleosts.
The oxygen consumption of excised skin (MO2 is.cut.) and the normal cutaneous oxygen uptake by the skin in situ from the external medium (MO2 ext.cut.) were investigated in seven species of teleosts in normoxic sea water: butterfish (Pholis gunnellus L.), cod (Gadus morhua L.), five-bearded rockling (Ciliata mustela L), shanny (Blennius pholis L.), flounder (Platichthys flesus L.), sole (Solea solea L.) and eel (Anguilla anguilla L.). In the butterfish, cod and rockling, all the oxygen absorbed by the skin is consumed by the skin tissue itself, whereas in the other species there is a net inward transcutaneous oxygen flux. The gain of oxygen through the skin is obtained either by a low MO2is.cut. (shanny, flounder) and/or by high MO2ext.cut. (sole and eel). The blind side of the sole is particularly efficient in oxygen uptake. The results are discussed in relation to the biota of the different species.


Anaphylactic shock due to kiwifruit.
A 44-year-old male patient was admitted to our emergency department (ED) with an episode of severe anaphylaxis displaying generalized urticaria and dyspnea 1 hour after consuming a kiwifruit. Initially, the patient reported discrete itching of his abdominal skin and was in moderate respiratory distress. The patient's wheal response and itch were attenuated 30 minutes after emergency treatment with intravenous antianaphylaxis drugs. However, he had symptoms of the chest distress, dizzy, and dysphoria. His vital signs exacerbated. After sufficient antianaphylaxis treatment, the patient's anaphylaxis shock symptoms had not been significantly improved. We reviewed the history. The patient had eaten a full fresh kiwifruit, so there may be some kiwifruit pulp left in the patient's stomach. After self-induced vomiting, the patient's clinical condition gradually improved without any changes in dosage of dopamine. After another 10 hours of observation and preventive therapy training, the patient was discharged. Cases of patients with anaphylactic reaction to kiwifruit and dragon fruit have not been reported yet. In the ED, it is easy to overlook the prolonged exposure to allergen in patients with oral allergy syndrome. If the patient has consumed much food or drugs to cause the allergic reaction, self-induced vomiting or gastric lavage to clean allergen may be useful.


Psychiatric illness among the mentally retarded. A swedish population study.
Object--The aim of this investigation was in the first place to study the relation between mental retardation and other mental disturbances. The second aim was to study the frequency of severe and mild mental retardation in an adult Swedish population and to throw some light on the socio-medical situation of the adult mentally retarded. Methods--A primary sample, stratified with respect to population density, was extracted from the population in the age group 20-60 years, resident in Kopparberg County, Sweden, on 1 July 1977. The mildly and severely mentally retarded in this sample were identified. Enquiry was made into the presence of additional handicaps in the mentally retarded. Social conditions including alcohol consumption and the occurrence of abuse and criminality were studied in the two retarded groups and a control group representing the rest of the population. The three groups were compared by rating with the Comprehensive Psychopathological Rating Scale (CPRS), by classification of any mental illness present according to the Diagnostic and Statistical Manual of Mental Disorders (DSM-III) and by determining their intake of psychotropic drugs and anti-epileptics. The mildly mentally retarded and the control group were also compared with respect to neuroticism and extraversion-introversion by rating with the Eysenck Personality Inventory (EPI). Results--The study revealed a prevalence of 0.27% for severe (IQ less than 53) and 0.32% for mild (IQ 53-73.7) mental retardation in the age group 20-60 years. All the severely retarded, but only just over half the mildly retarded, were known to the care authority. The majority of the former were living in some form of institution, whereas this applied to only 15% of the mildly retarded. Nineteen per cent of the severely retarded and 4% of the mildly retarded had manifest epilepsy. Defects of movement and of hearing were most prominent among the mildly retarded, while the frequency of specific speech disturbances was greater among the severely retarded, approximately 10% of whom had no power of verbal communication. Visual defects were recorded in about one-third of both groups. The study showed that alcohol intake was lower among both the severely and mildly mentally retarded than among the persons in the control group and that the frequency of abuse and criminality was as high among persons of higher intelligence as among the mentally retarded. The severely retarded, particularly the men, showed a raised psychiatric morbidity as compared with the mildly retarded and the control group.(ABSTRACT TRUNCATED AT 400 WORDS)


ROS: The Fine-Tuner of Plant Stem Cell Fate.
Reactive oxygen species (ROS) are initially considered to be toxic by-products of aerobic metabolism. However, accumulating evidence has shown that ROS also act as key regulators for the progression of several basic biological processes. Recent studies highlight the key role of ROS in root and shoot stem cell niche maintenance.


New megastigmane sesquiterpene and indole alkaloid glucosides from the aerial parts of Bupleurum chinense DC.
A new megastigmane sesquiterpene glucoside named chaihuxinoside A (1), and a new indole diglucoside named chaihuxinoside B (9) were isolated from the aerial parts of Bupleurum chinense DC. along with eight known compounds. Structures of two new compounds were elucidated by a combination of chemical and spectroscopic methods. Chaihuxinosides A and B were characterized as 11-hydroxyl-4-en-3,9-dioxo- megastigmane-11-O-beta-D-glucopyranoside (1), and 3-carboxy-indole-10-O-beta-D-glucopyranosyl(1-->2)-beta-D-glucopyranosyl ester (9), respectively.


PKC-dependent phosphorylation of Munc18a at Ser313 in activated RBL-2H3 cells.
Protein Kinase C (PKC) regulates the release of pro-inflammatory compounds from IgE/antigen-activated mast cells by unknown mechanisms. In this study, we show for the first time that PKC inhibitor Ro-03-0432, which inhibits RBL-2H3 exocytosis/degranulation in a concentration-dependent fashion, prevents the phosphorylation of membrane fusion factor Munc18a at Ser 313. Our study provides fresh evidence that PKC-dependent protein phosphorylation may contribute to the intricate regulation of mast cell degranulation by directly targeting the fusion factors.


Association of the GABRB3 gene with nonsyndromic oral clefts.
Nonsyndromic oral clefts are common craniofacial anomalies classified into two subgroups: cleft lip with or without cleft palate and isolated cleft palate. Nonsyndromic oral clefts are multifactorial diseases, with both genetic and environmental factors involved in their pathogenesis. The inhibitory neurotransmitter, gamma-aminobutyric acid plays a role in normal embryonic, and particularly facial, development and gamma-aminobutyric acid receptor type A beta-3 subunit (GABRB3) knockout mice have been shown to have cleft palate. The GABRB3 gene is therefore a strong candidate gene for nonsyndromic oral clefts. We investigated here whether genetic variations of the GABRB3 gene affect the risk for nonsyndromic oral clefts. In this case-control study, a total of 178 Japanese patients with cleft lip with or without cleft palate and 374 unrelated controls were recruited and were genotyped for six single nucleotide polymorphisms and a dinucleotide repeat marker of the GABRB3 gene. None of the single nucleotide polymorphisms showed complete linkage disequilibrium with other single nucleotide polymorphisms. In a case-control association study with the six-locus haplotype of the gene, TGTGCT haplotype frequency in patients with cleft lip with or without cleft palate was significantly higher than in the controls (corrected p value = .029). None of the alleles of the dinucleotide repeat marker showed significant association with cleft lip with or without cleft palate. Our data suggest that the GABRB3 gene is involved in the pathogenesis of cleft lip with or without cleft palate in the Japanese population.


Lipid-Lowering Therapy Utilization and Dosage Among Patients with Acute Coronary Syndrome Events: A Retrospective Cohort from 12 Community Hospitals.
Clinical practice guidelines recommend initiating a high-intensity LLT and continued monitoring of low-density lipoprotein cholesterol (LDL-C) following acute coronary syndrome (ACS). We used real-world data to describe LLT utilization after discharge and 1-year adherence. The reduction in LDL-C was also evaluated. Data were extracted from electronic health records (EHRs) from 12 hospitals in a large community healthcare system in midwestern United States between 2013 and 2019. Data on eligible patients recently discharged with an ACS event were linked to pharmacy claims data to describe LLT fill rates and 1-year post-discharge adherence. Adherence was reported as the proportion of days covered ≥80%. Of the 10,589 eligible patients, 49% filled a high-intensity statin at discharge and only 36% were adherent at 1 year. The mean (SD) age was 66.1±13.3, 39.3% were females, 58.8% were Caucasian, and 53.0% had Medicare. There was a clear trend for greater fill rates at discharge among patients with higher LDL-C values than those with lower values (p<0.01). Key predictors of high-intensity (versus medium-intensity) LLT use within 21 days after an ACS event included ACS type (odds ratio [OR] 0.59; 95% confidence interval [CI] 0.52-0.67 for NSTEMI versus STEMI), age group (OR: 0.59; 95% CI: 0.48-0.72 for >75 years versus <65 years), and statin use before index ACS event (OR: 1.56; 95% CI: 1.23-1.88). This real-world study found that despite recommendations in clinical practice guidelines, high-intensity LLT fill rates at discharge and 1-year adherence to LLT remain suboptimal. Clinical characteristics, including ACS type and LDL-C values, were strong predictors of filling and adherence to guideline-recommended therapy. Age, sex, and race/ethnicity disparities were observed in discharge fill rates and 1-year adherence. These results highlight the need for continued efforts at the patient and provider levels to improve LLT adherence among ACS patients.


Prostatic acid phosphatase. Biomolecular features and assays for serum determination.
Approximately 30 years ago, the finding that prostate acid phosphatase (PAP) was antigenically distinct from other acid phosphatases opened an era in the measurement of prostate cancer. Many immunoassays have been developed but their clinical significance has been limited. Studies comparing one or more assays in the same population of men with prostate cancer population have concluded that no differences were found in the sensitivities of the assays when the upper limits of normal were selected to provide equal specificities.


Topographical aspects of cerebellar degeneration.
Cerebellar Purkinje cells are arranged in longitudinal zones which differ in their connections and their biochemical properties. The significance of these patterns for the distribution of cerebellar degeneration is discussed.


The impact of age, body mass index, and fish intake on the EPA and DHA content of human erythrocytes.
n-3 FA are beneficial for cardiovascular health, reducing platelet aggregation, TG levels, and the risk of sudden death from myocardial infarction. The percentage of EPA + DHA in red blood cells (RBC), also known as the Omega-3 Index, has recently been proposed as a risk marker for death from coronary heart disease (CHD). The purpose of this study was to begin to explore the factors that can influence RBC EPA + DHA. We collected information on the number of servings of tuna or nonfried fish consumed per month, as well as on age, gender, ethnicity, smoking status, the presence of diabetes, and body mass index (BMI) in 163 adults in Kansas City who were not taking fish oil supplements. The average RBC EPA + DHA in this population was 4.9 +/- 2.1%. On a multivariate analysis, four factors significantly and independently influenced the Omega-3 Index: fish servings, age, BMI, and diabetes. The Index increased by 0.24 units with each additional monthly serving of tuna or nonfried fish (P < 0.0001), and by 0.5 units for each additional decade in age (P < 0.0001). The Index was 1.13% units lower in subjects with diabetes (P = 0.015) and decreased by 0.3% units with each 3-unit increase in BMI (P = 0.001). Gender or smoking status had no effect, and the univariate relationship with ethnicity vanished after controlling for fish intake. Given the importance of n-3 FA in influencing risk for death from CHD, further studies are warranted to delineate the nondietary factors that influence RBC EPA + DHA content.


Nicotine increases thermogenesis in brown adipose tissue in rats.
This study has tested the hypothesis that nicotine might increase thermogenesis in rats by activating the sympathetic nervous system which supplies brown adipose tissue. Three hours after a single injection of nicotine, both the turnover of norepinephrine and the binding of the purine nucleotide, guanosine 5'-diphosphate (GDP) to mitochondria from brown adipose tissue were significantly increased. After 11 days of treatment with nicotine, the turnover of norepinephrine and the GDP binding to mitochondria from brown adipose tissue both remained elevated but weight gain was not different. These data are consistent with the hypothesis that nicotine may have part of its effect through changes in thermogenesis involving sympathetic nervous activation of peripheral thermogenic tissues such as brown adipose tissue.


The immune system in critical illness.
The mammalian immune system comprises a complex network of physical and molecular elements that protect the individual from danger in the environment. An evolutionarily ancient innate immune system recognizes danger through pattern-recognition receptors that are encoded in the genome and mobilizes a rapid and potent but nonspecific response. This response is responsible for the clinical syndromes of sepsis and the multiple organ dysfunction syndrome. The adaptive immune system is highly selective in its targets and is endowed with memory but is slow in initial activation. Critical illness results in derangements of all components of the immune response, but the very complexity of the process has frustrated attempts to correct these derangements and to affect significantly the clinical course of sepsis.


Structure alterations and the spectral law of light diffusion during corneal edema.
The quantity D of light scattered by a layer is proportional of the n th power of the wavelength. This has been checked with five rabbit corneas at different stages of hydration and the corresponding values of n have been calculated. It appears that, during the progress of edema, D and n remain connected through the linear relation:n=aD+b. The constants a and b are determined as well as the correlation coefficients. That physical link between n and D throw a light on the nature of ultra-structure alterations occuring in the edematous stroma.


Arginase regulates red blood cell nitric oxide synthase and export of cardioprotective nitric oxide bioactivity.
The theory that red blood cells (RBCs) generate and release nitric oxide (NO)-like bioactivity has gained considerable interest. However, it remains unclear whether it can be produced by endothelial NO synthase (eNOS), which is present in RBCs, and whether NO can escape scavenging by hemoglobin. The aim of this study was to test the hypothesis that arginase reciprocally controls NO formation in RBCs by competition with eNOS for their common substrate arginine and that RBC-derived NO is functionally active following arginase blockade. We show that rodent and human RBCs contain functional arginase 1 and that pharmacological inhibition of arginase increases export of eNOS-derived nitrogen oxides from RBCs under basal conditions. The functional importance was tested in an ex vivo model of myocardial ischemia-reperfusion injury. Inhibitors of arginase significantly improved postischemic functional recovery in rat hearts if administered in whole blood or with RBCs in plasma. By contrast, arginase inhibition did not improve postischemic recovery when administered with buffer solution or plasma alone. The protective effect of arginase inhibition was lost in the presence of a NOS inhibitor. Moreover, hearts from eNOS(-/-) mice were protected when the arginase inhibitor was given with blood from wild-type donors. In contrast, when hearts from wild-type mice were given blood from eNOS(-/-) mice, the arginase inhibitor failed to protect against ischemia-reperfusion. These results strongly support the notion that RBCs contain functional eNOS and release NO-like bioactivity. This process is under tight control by arginase 1 and is of functional importance during ischemia-reperfusion.


The host response in secondary hydatidosis of mice. I. Circulating antibodies.
The infection of young albino mice by the intraperitoneal injection of viable hydatid protoscolices provided a suitable model for the investigation of the factors controlling the subsequent host immune response. Antibodies detectable by haemagglutination and complement fixation appeared around the 14th week after infection. Increases in antibody titres were related to the potency of the antigenic impulse(s) produced by the healthy germinal membrane and viable protoscolices. Our results suggest that qualitative and quantitative variations in excretory, secretory and somatic antigens, occurring during the different phases of parasite development, incite the production of a multitude of antibodies, only a few of which are detectable by conventional methods.


Melanin and humic acid-like polymer complex from olive mill waste waters. Part I. Isolation and characterization.
A water soluble humic acid and melanin-like polymer complex (OMWW-ASP) was isolated from olive mill waste waters (OMWW) by ammonium sulfate fractionation to be used as natural additive in food preparations. The dark polymer complex was further characterized by a variety of biochemical, physicochemical and spectroscopic techniques. OMWW-ASP is composed mainly of proteins associated with polyphenols and carbohydrates and the distribution of its relative molecular size was determined between about 5 and 190 kDa. SDS-PAGE shows the presence of a well separated protein band of 21.3 kDa and a low molecular weight peptide. The OMWW-ASP complex exhibits a monotonically increasing UV-Vis absorption spectrum and it contains stable radicals. Antioxidant activity measurements reveal the ability of the OMWW protein fraction to scavenge both the cationic 2,2'-azino-bis-(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS(+)) radical, as well as the stable nitroxide free radical 4-hydroxy-2,2,6,6-tetramethylpiperidine 1-oxyl (TEMPOL).


[Characteristics of physical therapy in internal medicine].
Internal physiotherapy is interpreted as supplementary level of performance (clinical feature--aim of therapy--means of physiotherapy) both of the internal specialist and the physiotherapeutist. It is particularly referred to the commonness of the responsibility for the aim of therapy. The importance of the phase of the disease when the plan of therapy is established is described.


Management of Orbital Involvement in Sinonasal and Ventral Skull Base Malignancies.
The orbit may be frequently involved by sinonasal or ventral skull base malignancy. This involvement bodes a poorer prognosis for survival. Multimodality therapy with surgery and radiation therapy is usually attempted to optimize local control and overall survival. Oncologic surgical resection with negative margins is critical to local control and survival. In the past, any involvement of the orbit was deemed to necessitate orbital sacrifice. However, contemporary studies show that in carefully selected cases, orbital preservation does not adversely impact survival. In addition, novel reconstructive techniques can help minimize complications and optimize functional and aesthetic outcomes.


Antihypertensive treatment in elderly hypertensives without a history of stroke and the risk of cognitive disorders.
The role of the antihypertensive therapy in preventing cognitive disorders in elderly persons without a history of stroke is a matter of debate. This review focuses on the pathogenesis of the cognitive disorders in elderly hypertensives and on the risk factors of their occurrence. Relevant papers were identified by searches in PubMed from 1946 until October 2007, using the key words 'vascular risk factors', 'vascular cognitive impairment', 'vascular dementia', 'neuroimaging in hypertension' and 'antihypertensive treatment'. Blood pressure lowering in elderly patients with long-standing hypertension below a certain critical level may increase the risk of cerebral hypoperfusion and cognitive decline, particularly in cases with additional vascular risk factors. Cerebral white matter lesions have been found in the majority of elderly hypertensives. They have been shown to correlate with cognitive disorders. Appropriate neuropsychological assessment and follow-up of the cognitive functions could be considered with the aim to individualize the antihypertensive therapy and slow down cognitive decline. Prospective studies are needed to confirm such a treatment strategy.


Investigation of distortion and damage of molybdenum†silicon multilayer reflective coatings with high-intensity ultraviolet radiation.
Studies are performed to determine an upper limit on the optical damage threshold of a soft-x-ray molybdenum-silicon multilayer reflective coating by the use of a 308-nm, 15-ns pulse from a Xe-Cl excimer laser in order to simulate the potential damage induced by the x-ray flux from a pulsed laser-produced plasma. Experimental results yield a value of 0.26 J/cm(2) to produce visible signs of damage as determined by optical microscopy. Experiments are conducted first on silicon, as a reference point of a bulk material, and then applied to molybdenum-silicon in an effort to facilitate a theoretical comparison between a simple and a more complicated material. Theoretical predictions are in reasonable agreement with experimental results, but suggest that a lower value of 0.085 J/cm(2) might cause significant thermal-induced damage.


Hepatitis B and liver cancer among three Asian American sub-groups: a focus group inquiry.
Prevalence of hepatitis B among Asian Americans is higher than for any other ethnic group in the United States. Since more than 50% of liver cancer is hepatitis B related, the burden of morbidity and mortality is extremely high among Asian Americans, highlighting the need for culturally appropriate interventions. We conducted focus groups (n = 8) with a total of 58 Korean, Vietnamese, and Chinese immigrants in Maryland to explore knowledge, awareness and perceived barriers toward hepatitis B screening and vaccinations. Thematic analysis uncovered generally low levels of knowledge and awareness of hepatitis B risks, screening, and vaccination; inter-generational differences; and barriers to prevention. Some differences arose across ethnic groups, particularly toward perceived orientation to preventive activities and the role of religious groups. High rates of hepatitis B infection among Asian Americans highlight the need for tailored interventions. These findings may assist policy strategists in implementing interventions that will facilitate the integration and scale-up of hepatitis B education, screening, and vaccination campaigns.