Import of proteins into mitochondria. Import and maturation of the mitochondrial intermembrane space enzymes cytochrome b2 and cytochrome c peroxidase in intact yeast cells.
The import of cytochrome b2 and cytochrome c peroxidase into mitochondria was investigated by pulse-chase experiments with intact yeast cells combined with subcellular fractionation. Import and processing of the precursors of these intermembrane space proteins is blocked by uncouplers of oxidative phosphorylation, indicating that an "energized" inner membrane is required. Cytochrome b2 is processed in two steps. The first step involves energy-dependent transport across both mitochondrial membranes and cleavage by a matrix-located protease to yield an intermediate which is smaller than the precursor, but larger than the mature protein. The second step involves conversion of the intermediate to the mature form. Whereas the precursor and the mature form are soluble, the intermediate is membrane-bound and exposed to the intermembrane space. The maturation of cytochrome c peroxidase is much slower than that of cytochrome b2. Proteolytic processing rather than import is rate-limiting since cytochrome c peroxidase precursor labeled during a 3-min pulse is already found attached to the outer face of the mitochondrial inner membrane. Import of cytochrome b2 and probably also of cytochrome c peroxidase thus involves energy-dependent transport to the matrix and cleavage by a matrix-localized protease. Maturation of cytochrome b2 proceeds in the sequence: soluble precursor leads to membrane-bound intermediate form leads to soluble mature form.


Severe bronchospasm followed by respiratory arrest during thallium-dipyridamole imaging.
We describe the occurrence of sudden severe bronchospasm and respiratory arrest following dipyridamole infusion in a patient with chronic obstructive pulmonary disease predominantly of the emphysematous type. The severe reaction was unexpected because the patient had tolerated well withdrawal of aminophylline derivatives for 48 hours and was receiving chronic prednisone 20 mg qd. Although the diagnostic and prognostic gains from dipyridamole imaging far outweigh the small risk associated with the test, patients with chronic pulmonary obstructive disease must be closely monitored during thallium-dipyridamole imaging.


[The role of preventive chemotherapy in the present tuberculosis epidemiology of GDR (author's transl)].
The risk of "Gesunde Befundträger" (healthy carriers of pulmonary lesions) to develop pulmonary tuberculosis is compared with that of persons with X-ray shadows in the lung. In the group of "Gesunde Befundträger" this risk can be further differentiated, being highest among males with positive tuberculin skin test and more extended X-ray shadows in the lung. Judging from a follow-up of 4 years in the double-blind trial on isoniazid preventive treatment in persons with fibrotic lesions, the risk of developing pulmonary tuberculosis is reduced by 2/3 by giving 300 mg isoniazid daily during 24 weeks. In the present epidemiological stage of tuberculosis in GDR, preventive treatment of persons with highest risk of developing tuberculosis disease is the most promising prophylactic measure. The recommedations to reduce side-effects must be observed.


The mannose 6-phosphate/insulin-like growth factor II receptor is a nanomolar affinity receptor for glycosylated human leukemia inhibitory factor.
Comparison of the binding properties of non-glycosylated, glycosylated human leukemia inhibitory factor (LIF) and monoclonal antibodies (mAbs) directed at gp190/LIF-receptor beta subunit showed that most of the low affinity (nanomolar) receptors expressed by a variety of cell lines are not due to gp190. These receptors bind glycosylated LIF produced in Chinese hamster ovary cells (CHO LIF) (Kd = 6.9 nM) but not Escherichia coli-derived LIF or CHO LIF treated with endoglycosidase F. CHO LIF binding to these receptors is neither affected by anti-gp190 mAbs nor by anti-gp130 mAbs and is specifically inhibited by low concentrations of mannose 6-phosphate (Man-6-P) (IC50 = 40 microM), suggesting that they could be related to Man-6-P receptors. The identity of this LIF binding component with the Man-6-P/insulin-like growth factor-II receptor (Man-6-P/IGFII-R) was supported by several findings. (i) It has a molecular mass very similar to that of the Man-6-P/IGFII-R (270 kDa); (ii) the complex of LIF cross-linked to this receptor is immunoprecipitated by a polyclonal anti-Man-6-P/IGFII-R antibody; (iii) this antibody inhibits LIF and IGFII binding to the receptor with comparable efficiencies; (iv) soluble Man-6-P/IGFII-R purified from serum binds glycosylated LIF (Kd = 4.3 nM) but not E. coli LIF. The potential role of Man-6-P/IGFII-R in LIF processing and biological activity is discussed.


Nonoperative management of esophageal strictures following esophagomyotomy for achalasia.
The optimal management of reflux-induced esophageal strictures that occur after esophagomytomy for achalasia is uncertain. This paper presents our experience with the nonsurgical treatment of postesophagomyotomy strictures in achalasia patients using endoscopic dilation and gastric acid suppression. Six patients with achalasia who had undergone prior esophagomyotomy subsequently developed recurrent dysphagia and were found to have an esophageal stricture. Esophagrams typically showed a markedly dilated esophagus with a narrowed, sharply angulated gastroesophageal junction. Esophageal manometry confirmed esophageal aperistalsis and, when measured, the LES pressure was < 5 mm Hg. Endoscopy showed esophageal inflammation and a fixed stricture at the gastroesophageal junction. Strictures were dilated under direct visualization using through-the-scope balloon dilators. Patients began gastric acid suppressive treatment at the same time. Five patients who remained symptomatic underwent repeat endoscopy, which demonstrated improvement in esophagitis. Dilation was then repeated with a larger balloon dilator. Over a mean follow-up period of 3.8 years, the average number of repeat dilations per patient was 3.6 (range: 0-12). All patients had symptomatic improvement and weight gain. No patient required surgery. We conclude that esophageal strictures after esophagomyotomy for achalasia can be safely treated using endoscopic dilation and gastric acid suppression, thus avoiding the need for reoperation.


Computer-generated diagnostic correction of anterior diastemas.
A technique for pretreatment estimation of appearance following cosmetic change to the anterior teeth by using a computer-generated image has been described. Patients should be advised that the generated projection is an estimation. As with a diagnostic set-up, a computer-generated result can only approximate final treatment. The patient must understand that the result could vary for reasons that might include (1) restorative material, (2) functional occlusal needs, (3) gingival tissue irritability, (4) artificial versus outdoor light, and (5) the angle at which the photograph was made. As technology advances, there will undoubtedly be other applications for computer graphics. The authors have successfully estimated outcomes for prosthodontic, orthodontic, and orthognathic surgical treatment. If properly used, color computer estimations can be successfully integrated in a dental office as a communication tool for the dentist, patient, and laboratory technician.


Pulmonary granuloma formation in the rat is partially dependent on monocyte chemoattractant protein 1.
We have examined the role of MCP-1 (monocyte chemoattractant protein 1; also known as monocyte chemotactic and activating factor or the murine JE gene product) in the pathogenesis of glucan-induced granulomatous vasculitis in the rat. While in vitro studies indicate that MCP-1 possesses monocyte chemotactic and activating activities, little is known about its biologic role in pathologic processes. Glucan-induced pulmonary granulomatous vasculitis is an ideal model in which to study the role of MCP-1, because the granulomas develop rapidly and synchronously and are monocyte/macrophage-rich. The purpose of this study was to define the topographic distribution and temporal pattern of MCP-1 expression in the lungs of rats with evolving glucan-induced granulomatous vasculitis and to determine the effect of neutralization of MCP-1 activity on granuloma formation. Glucan-induced pulmonary granulomatous vasculitis was induced in rats by the intravenous infusion of yeast cell wall glucan. At the indicated time points after glucan infusion, rats were sacrificed and the lungs processed for Northern, immunohistochemical and in situ hybridization analyses of MCP-1 production. Morphometric analysis was used to quantify the effect of neutralization of MCP-1 activity on granuloma formation. Granuloma formation was accompanied by a biphasic increase in steady-state whole lung MCP-1 mRNA levels that peaked at 1 and 6 to 24 hours. In situ hybridization and immunohistochemical analyses revealed that components of the bronchial and vascular walls are responsible for the early rise (1 hour) in MCP-1 mRNA and protein expression, whereas granuloma-associated alveolar macrophages are the predominant source of MCP-1 later (6 to 24 hours) in the evolution of these lesions. Intravenous infusion and/or intratracheal instillation of neutralizing concentrations of anti-rat MCP-1 antibody raised against recombinant rat MCP-1 resulted in a dramatic decrease in the number and size of glucan-induced granulomas as well as in the numbers of mononuclear phagocytes retrieved in bronchoalveolar lavage fluid. These studies demonstrate that glucan-induced granulomatous vasculitis is accompanied by increased local expression of MCP-1 mRNA and protein, that there is a coordinated production of MCP-1 by different cell types within the lung during evolving glucan-induced pulmonary vasculitis, and that MCP-1 plays a requisite role in pulmonary granuloma formation.


Prolactin response to growth hormone-releasing hormone during chronic thyrotropin-releasing hormone infusion in the treatment of amyotrophic lateral sclerosis.
In six patients suffering from amyotrophic lateral sclerosis we evaluated changes of T4, T3, TSH, PRL, and GH during treatment by continuous iv infusion of TRH for at least 15 days. No clinical improvement was detected. A significant rise of thyroid hormone levels was observed, as well as an upward trend of basal TSH levels and no change of basal PRL and GH levels. TRH acute test-induced TSH and PRL responses became blunted. Treatment provoked also the onset of a responsiveness of PRL to GHRH. The reduced TSH and PRL responses to acute TRH test during treatment could be explained by a down-regulation of TRH pituitary receptors. On the contrary, the onset of PRL responsiveness to GHRH is at present without a satisfactory explanation.


The self-concepts of regular transcendental meditators, dropout meditators, and nonmeditators.
Regular meditators, dropout meditators, and nonmeditators were administered the Tennessee Self Concept Scale twice over a six month period (N = 32 Australian men and women). Results showed that regular meditators as compared to dropout meditators were found to have significantly fewer of the characteristics associated with psychosis. Nonmeditators as compared to dropout meditators were found to have significantly fewer characteristics associated with psychosis and personality integration. Regular meditators as compared to nonmeditators have a more positive perception of their behavior. The findings provide a personality description of the dropout meditators which may be useful for screening prospective meditators.


Parent perceptions of the psychological functioning of their children diagnosed with pediatric motility disorders and that of family members.
The aim of our study was to characterize the parental perceptions of the behavioral and emotional functioning of their children and families coping with gastrointestinal motility disorders. The American Pseudo-obstruction and Hirschsprung's disease Society sponsored an educational meeting for parents of children afflicted with a variety of pediatric gastrointestinal motility disorders. During the conference, parents completed a questionnaire pertaining to the behavioral and emotional functioning of the afflicted child and other family members. Parents perceived that the child's illness was more difficult on the parents than on the affected child or their siblings. Also, parents perceived support from professionals, family, and friends increased after the children were diagnosed with pediatric gastrointestinal motility disorders. Parents worried most about the health and medical management of their afflicted child. The most common behavioral problem of the afflicted children was fear of separation, whereas the most common behavioral problem of their siblings was jealousy. The majority of referrals to mental health professionals resulted from parental emotional problems or marital discord.


Purification of brain peroxisomes and localization of 3-hydroxy-3-methylglutaryl coenzyme A reductase.
At least three different subcellular compartments, including peroxisomes, are involved in cholesterol biosynthesis. Because proper CNS development depends on de novo cholesterol biosynthesis, peroxisomes must play a critical functional role in this process. Surprisingly, no information is available on the peroxisomal isoprenoid/cholesterol biosynthesis pathway in normal brain tissue or on the compartmentalization of isoprene metabolism in the CNS. This has been due mainly to the lack of a well-defined isolation procedure for brain tissue, and also to the presence of myelin in brain tissue, which results in significant contamination of subcellular fractions. As a first step in characterizing the peroxisomal isoprenoid pathway in the CNS, we have established a purification procedure to isolate peroxisomes and other cellular organelles from the brain stem, cerebellum and spinal cord of the mouse brain. We demonstrate by use of marker enzymes and immunoblotting with antibodies against organelle specific proteins that the isolated peroxisomes are highly purified and well separated from the ER and mitochondria, and are free of myelin contamination. The isolated peroxisomal fraction was purified at least 40-fold over the original homogenate. In addition, we show by analytical subcellular fractionation and immunoelectron microscopy that HMG-CoA reductase protein and activity are localized both in the ER and peroxisomes in the CNS.


[The protective effect of PEP-1-CAT fusion protein on hydrogen peroxide-induced oxidative stress injury in human umbilical vein endothelial cells].
To investigate the transduction ability of PEP-1-CAT fusion protein into human umbilical vein endothelial cell (HUVECs) and the effects on hydrogen-peroxide (H2O2)-induced oxidative stress injury in these cells. With the use of TA-cloning program and isocaudamer technique, the pET15b-PEP-1-CAT of prokaryotic expression plasmid was successfully constructed. The recombinant plasmid was transformed into E.coli BL21 (DE3) and the protein expression was induced by IPTG. The recombinant protein has an N-terminal His-tag which could be used to purify the target protein by affinity chromatography on a Ni2+-NTA-resin column. The fusion protein PEP-1-CAT was prepared and confirmed by specific enzyme activity in vitro. The purified PEP-1-CAT fusion protein was added on cultured HUVECs in vitro. The transduction ability of PEP-1-CAT fusion protein into cells was analyzed by Western blot and specific enzyme activity. The cells were treated with H2O2 (0.5 mmol/L) alone and in combination with PEP-1-CAT fusion protein for 4 h. Then, the cell viability, lactate dehydrogenase (LDH) and malondialdehyde (MDA) contents were measured. The PEP-1-CAT fusion protein could be transduced into the cultured HUVECs in a dose- and time-dependent manner and be stable for at least 48 h. After H2O2 administration, cell viability was significantly reduced compared with control group (37.23%+/-5.68% vs. 100%, P<0.05), while LDH leakage (849.3 U/L+/-95.1 U/L) and MDA (8.23 nmol/L+/-1.58 nmol/L) content were significantly higher than that in control group (540.6 U/L+/-65.7 U/L and 2.46 nmol/L+/-1.42 nmol/L, respectively, all P<0.05). Preincubation with PEP-1-CAT proteins at various concentrations (0.25-2 micromol/L) significantly attenuated H2O2-induced cell injury. The PEP-1-CAT fusion protein could efficiently penetrate HUVECs and the transduced protein could attenuate cellular oxidative stress injury induced by H2O2. The PEP-1-CAT fusion protein might be a new strategy for preventing and treating oxidative stress induced diseases.


N-n-butyl haloperidol iodide protects cardiac microvascular endothelial cells from hypoxia/reoxygenation injury by down-regulating Egr-1 expression.
Our previous studies have shown that N-n-butyl haloperidol iodide (F2) can antagonize myocardial ischemia/reperfusion (I/R) injury by down-regulating the early growth response (Egr)-1 expression, but the molecular mechanisms are not well understood. Because there is evidence implicating myocardial I/R injury is closely associated with endothelial dysfunction. The present study is to test the hypothesis that the protective effects of F2 on myocardial I/R injury is related closely with down-regulating Egr-1 expression on cardiac microvascular endothelial cells (CMECs). A model of cultured CMECs exposed to hypoxia/reoxygenation (H/R) was developed. With antisense Egr-1 oligodeoxyribonucleotide (ODN), the relationship between Egr-1 expression and endothelial H/R injury was investigated. Egr-1 mRNA and protein expression were examined by real-time fluorescent quantitative PCR, immunocytochemical staining and Western-blot analysis. Lactate dehydrogenase (LDH), malondialdehyde (MDA), superoxide dismutase (SOD), intercellular adhesion molecule-1 (ICAM-1), adherence of neutrophil and platelets, and cell viability were measured after H/R to evaluate the degree of endothelial injury. Pretreatment with antisense Egr-1 ODN significantly reduced Egr-1 protein expression and attenuated injury of CMECs. Consistent with down-regulation of Egr-1 expression by F2, inflammation and other damage were significantly reduced as evidenced by a decrease of ICAM-1 expression, reduction of neutrophil and platelets adherence, increase in SOD, and decreases in MDA and LDH levels, resulting in the rise of cell viability. We demonstrate a protective effect of F2 in CMECs against H/R injury by down-regulating Egr-1 expression, which might be play a vital role in the pathogenesis of myocardial I/R injury.


A preliminary, randomized trial of psychoeducation for women with borderline personality disorder.
The main objective of this study was to determine whether being taught the latest information concerning borderline personality disorder (BPD) leads to a decline in core BPD symptoms and an improvement in psychosocial functioning. Fifty-five late adolescent women participated in a rigorous diagnostic assessment and 50 met DIB-R and DSM-IV criteria for BPD. All 50 were informed that they met criteria for BPD. Then 30 were randomized to a psychoeducation workshop that took place within a week of diagnostic disclosure. The other 20 were assigned to a waitlist and participated in the workshop at the end of this 12-week study. The two primary outcome measures were readministered each week of the trial: the Zanarini Rating Scale for DSM-IV Borderline Personality Disorder (ZAN-BPD) and the Sheehan Disability Scale (SDS). Immediate psychoeducation concerning the BPD diagnosis was associated with a significantly greater decline in general impulsivity and the storminess of close relationships. However, it did not result in significantly improved psychosocial functioning. Taken together, the results of this study suggest that informing patients about BPD soon after diagnostic disclosure may help to alleviate the severity of two of the core elements of borderline psychopathology-general impulsivity and unstable relationships. They also suggest that such instruction may prove to be a useful and cost-efficient form of pre-treatment.


Nuclear prostaglandin signaling system: biogenesis and actions via heptahelical receptors.
Prostaglandins are ubiquitous lipid mediators that play pivotal roles in cardiovascular homeostasis, reproduction, and inflammation, as well as in many important cellular processes including gene expression and cell proliferation. The mechanism of action of these lipid messengers is thought to be primarily dependent on their interaction with specific cell surface receptors that belong to the heptahelical transmembrane spanning G protein-coupled receptor superfamily. Accumulating evidence suggests that these receptors may co-localize at the cell nucleus where they can modulate gene expression through a series of biochemical events. In this context, we have recently demonstrated that prostaglandin E2-EP3 receptors display an atypical nuclear compartmentalization in cerebral microvascular endothelial cells. Stimulation of these nuclear EP3 receptors leads to an increase of eNOS RNA in a cell-free isolated nuclear system. This review will emphasize these findings and describe how nuclear prostaglandin receptors, notably EP3 receptors, may affect gene expression, specifically of eNOS, by identifying putative transducing elements located within this organelle. The potential sources of lipid ligand activators for these intracellular sites will also be addressed. The expressional control of G-protein-coupled receptors located at the perinuclear envelope constitutes a novel and distinctive mode of gene regulation.


Characterization of baroreceptor-related neurons in the monkey insular cortex.
Insular neurons responsive to baroreceptor challenge have been identified in the rat, but not previously in primates. Characterization of baroreceptor-related neurons was performed in 15 anesthetized monkeys (Macaca fascicularis) using extracellular single-unit recording techniques. 131 units were investigated within the insula and surrounding regions. Based on their responses to phenylephrine hydrochloride (PE) and sodium nitroprusside (SNP), three types of units were distinguished: 35/131 (27%) sympathoexcitatory (SE), 12/131 (9%) sympathoinhibitory (SI) and 84 (64%) null units. More baroreceptive units were found within the insula (38/73, 52%) than in surrounding areas (9/58, 16%) (p < 0.001). Lateralization was indicated with more baroreceptive units being encountered within the right insula (28/44, 64%) than the left (10/29, 34%) (p = 0.02). The majority of the responsive units were located within the dysgranular and granular insula in layers II, III and V/VI. These data suggest that cardiovascular representation may occur in the primate insula as has been shown in other species.


Induction of growth rate and transcriptional modulation of growth promoters and growth inhibitors in epithelial cells by EBV-LMP1.
LMP1 is a genuine oncogene encoded by the Epstein-Barr virus (EBV). The cellular response to expression of the EBV-encoded gene LMP1 in the epithelial cell line Wish was studied. Cells were stably transfected with pCEP-LMP, an expression vector for LMP1. On transcript level a transient expression of the LMP1-gene with a maximum 2 days post transfection was observed. Six days post transfection the rate of DNA synthesis of LMP1-transfected Wish cells was increased by 80% compared to control cells, after 2 further days the number of cells was increased by 32%. A human cDNA-array was screened with probes from LMP1-transfected and control cells showing induction of transcription for proliferation associated genes and repression for growth suppressor genes.


The suitability of hepatocyte culture models to study various aspects of drug metabolism.
Since the liver is the main organ involved in the metabolism and the toxicity of xenobiotics, isolated rat hepatocytes have been increasingly used in recent years as a model to identify pharmacological and toxicological responses of drugs. However, it is generally recognised that isolated hepatocytes retain most of their functions only for a short period. For this reason, numerous models and techniques have been developed to study and improve the metabolic capacity of hepatocytes in vitro over an extended time period and in application for drug metabolism studies. In the present study, we compared four different cell culture models to fulfill these requirements and have therefore harvested hepatocytes and cultured them in different culture systems over two weeks. In order to prove certain advantages or disadvantages of each model, we compared the metabolic capacity, albumin secretion, the release of cytosolic and mitochondrial enzymes, as well as the capacity to metabolise diclofenac (DF). We found that rat hepatocytes in all studied culture models (except the Unisyn Bioreactor) were able to metabolise DF to the same extent as found in vivo. However, the concentration of metabolites was found to decrease with culture time using the monolayer although the DF metabolite level in the collagen Sandwich culture was higher than that of the monolayer culture. The 3D-membrane bioreactor preserved the metabolic capacity for a prolonged period of time. The concentrations of DF metabolites in the Unisyn hollow fiber bioreactor were below the detection limit, which corresponded to other parameters such as albumin secretion and cytochrome P450 activity, disqualifying this culture system clearly for the use of in vitro primary hepatocyte cultures. The other three systems all have their place in drug metabolism with different advantages. However, our studies clearly showed that hepatocytes cultured within a collagen sandwich or in the 3D-membrane bioreactor qualify to study various aspects of drug metabolisms over a long time period. Further studies are needed to prove if the later two culture models may really help to reduce animal testing.


Combined hepatocellular and cholangiocarcinoma: a clinicopathologic study of 26 resected cases.
Combined hepatocellular and cholangiocarcinoma (cHCC-CC) is an uncommon subtype of primary liver cancer, the clinicopathological features of which have rarely been reported in detail. The aim of this study was to clarify the characteristics of cHCC-CC in comparison with hepatocellular carcinoma (HCC) and cholangiocarcinoma (CC). The clinicopathological features of 26 cHCC-CC patients, who were surgically treated, were reviewed by comparing them with the features of patients suffering from ordinary hepatocellular carcinoma (HCC) and cholangiocarcinoma (CC). The cHCC-CC patients showed greater similarity with HCC patients than with CC patients with regard to male/female ratio, status of hepatitis viral infection, serum alpha-fetoprotein (AFP) level, and non-tumor liver histology. The disease stage of the cHCC-CC patients was more advanced than that of either the HCC or CC patients. The cHCC-CC tumors were significantly more invasive to the portal vein than the HCC tumors and were comparable to the CC tumors. The overall 3-, 5-, and 10-year survival rates and the median survival times (95% confidence interval) were 34.6%, 23.1%, 11.5% and 1.8 (0.7-3.0) years for cHCC-CC patients, 86.7%, 66.2%, 46.8% and 4.6 (4.3-5.0) years for HCC patients, and 68.5%, 32.3%, 23.9% and 1.9 (1.1-2.7) years for CC patients, respectively. Survival of patients with cHCC-CC was significantly poorer than that of HCC or CC patients. Among the 26 patients, six survived for >5 years. In most cases, cHCC-CC seems to be a variant of ordinary HCC with cholangiocellular features, rather than a true intermediate disease entity between HCC and CC. The surgical approach is recommended for selected patients with cHCC-CC.


Host defence capacities of pulmonary surfactant: evidence for 'non-surfactant' functions of the surfactant system.
The most well characterized function of pulmonary surfactant is its ability to reduce surface tension at the alveolar air-liquid interface, thereby preventing lung collapse. However, several lines of evidence suggest that surfactant may also have 'non-surfactant' functions: specific components of surfactant (proteins and phospholipids) may interact with different alveolar cells, inhaled particles and micro-organisms modulating pulmonary host defence systems. SP-A, the most abundant surfactant protein, binds to alveolar macrophages via a specific surface receptor with high affinity [128]. Such binding effects the release of reactive oxygen species from resident alveolar macrophages if SP-A is properly presented to the target cell. SP-A also stimulates chemotaxis of alveolar macrophages [142], and serves as an opsonin in the phagocytosis of herpes simplex virus [161] Candida tropicalis [138] and various bacteria [137]. In addition, SP-A enhances the uptake of particles by monocytes and culture-derived macrophages [140] and improves bacterial killing. SP-D, another hydrophobic surfactant-associated protein, might interact with alveolar macrophages as well, stimulating the release of oxygen radicals [148], while for the hydrophilic surfactant proteins SP-B and SP-C no macrophage interactions have been described so far. SP-A and SP-D are members of the so-called 'collectins', pattern recognition molecules involved in first line defence. While some surfactant proteins appear to stimulate certain macrophage defence functions, surfactant phospholipids seem to inhibit those of lymphocytes. Suppressed lymphocyte functions include lymphoproliferation in response to mitogens and alloantigens, B cell immunoglobulin production and natural killer cell cytotoxicity. Concerning surfactant's phospholipid composition phosphatidylglycerol is more suppressive than phosphatidylcholine on a molar basis [38]. Bovine surfactant has an immunosuppressive effect on the development of hypersensitivity pneumonitis in a guinea pig model [150]. Despite these interesting observations, several important questions concerning the interactions of surfactant components with pulmonary host defence systems remain unanswered. Sufficient host defence in the lungs works through various humoral-cellular systems in conjunction with the specific anatomy of the airways and the gas exchange surface--how does the surfactant system fit into this network? Surfactant and alveolar cells are both altered during lung injury--is there a relationship between alveolar cells from RDS patients and the endogenous surfactant isolated from such patients? How does exogenous surfactant as used for substitution therapy modulate the defence system of the host? Some of those artificial surfactants have been shown to inhibit the endotoxin-alveolar macrophages, PMNs and monocytes including IL-1, IL-6 and TNF [139,152].(ABSTRACT TRUNCATED AT 400 WORDS)


[Current knowledge on resorption of the edentulous alveolar ridge].
Due to inside physiological processes of the bone tissue of the residual ridge, the above is identical with the bone tissue in other parts of the body. All bones which contain a larger percentage of substance spongiosa are very sensitive to the changes in remodelation. In mandibula the arrangement of the bone trabeculas is in the same direction with the spongious bone traectoria. In maxillae, functional demands for transmitting the forces, are fulfilled by a larger number of trabeculas per square unit. The atrophia of the residual ridge was a result of teeth loss, which means that there was no working tension on the bone, affected by the periodontal ligament in a physiological way. The resent knowledge of the above problems indicates that inflammation and pressure which develop under the mobile denture cause an intensive process of resorption of edentulous arch. In periodontitis the connection between lymphocytes and other inflammatory cells on one side, and the residual bone resorption level on the other side, were proved by stereometrical methods. The ELISA method proved that cytokine interleukin-1 beta (IL-1 beta), IL-1 beta and the tumor necrosis factor alpha, were the major factors in the stimulation of bone resorption, and inhibitatory of the above, as well. Mononucleous blood cells under the influence of the Porphyromonas gingivalis were forming interleukin-1 which explains that the etiology of bone resorption can be affected by the infection, too. It has been proved that there is a direct relation between the pressure under the mobile denture and the residual ridge resorption level on the other side. It seems that the frontal areas of the edentulous are more susceptible to resorption. It is considered that the orthopantomography is the most acceptable method in level measuring of the reduction of residual ridge. The advantages of the above method are simplicity, precision, repeating possibilities, and comparation of the radiographs in time interval which makes it possible to control the development of changes. Densitometric measuring of osteoporotic changes is also possible, due to above method. The scientific contribution to research and prevention of negative consequences of the residual ridge resorption is the most valuable. Tere were many possibilities in using the indirect physiological role of piezoelectric field on the osteoclasts and activation by the AKMA. The effect of the fluor in drinking water as the element which has preventive role in reduction of the residual ridge, has been established. Due to the fact that the occlusal pressure which transmits itself through the mobile denture has an important role in resorption of the residual ridge, acts of terciare prevention include application of soft acrylates and reduction of occlusal surface.


Alcoholic beverage server liability and the reduction of alcohol-involved problems.
Legal liability of alcoholic beverage servers has been suggested as a means to stimulate preventive serving practices and thus reduce alcohol-involved problems. A number of variables contribute (both negatively and positively) to the potential of such liability and a conceptual model that links these variables was developed. In this project, an expert legal panel was used to identify and rate the major legal factors contributing to server liability. As a result each state was ranked according to its relative level of liability exposure. States that ranked highest in server liability were found to have more publicity about such liability, greater awareness and higher concern among licensed establishment owners/managers and different serving practices compared to states with lowest liability exposure. As a result we conclude that server liability has a real potential for reducing alcohol-involved problems but additional research is needed.


[EFFECT OF FLUCONAZOLE ON TEMPORAL ORGANIZATION OF BIOLOGICAL PROPERTIES OF CANDIDA ALBICANS].
AIM. Study the effect of fluconazole antimycotic on temporal organization of biological properties of Candida albicans. Clinical isolates and a museum C. albicans strain were used. The study was carried out for 24 hours with a 4 hour interval, determining proliferative, adhesive, morphological, protease, catalase, phospholipase activity. The results of the study were treated statistically. Maximal sensitivity to fluconazole was established for the museum C. albicans strain during the day, in clinical isolates--in the evening and at night. After the effect of 1/2 minimal inhibitory concentration (MIC) of the preparation, the rhythms of all the parameters changed in the museum culture from circadian to ultradian: The preparation reduced mesor and amplitude of the oscillation of proliferative and adhesive activity, but did not have an effect on chrono-infrastructure of morphogenesis and aggression enzymes. The temporal rows of biological activity of pathogenic C. albicans isolates after the incubation with fluconazole were characterized by synchronization of all the properties in a narrow temporal interval from 07:00 to 11:00 and from 16:00 to 23:00 hours. The results obtained give evidence on the lability of adhesion factors and colonization and stability of virulence factors in the museum variant. A clear synchronization in time of all the pathogenicity factors of clinical isolates gives evidence on the economy of material and energy resources, opening a perspective of using the chronobiological approach in antibiotics therapy of candidoses.


Numerical simulation of airflow and microparticle deposition in a synchrotron micro-CT-based pulmonary acinus model.
The acinus consists of complex, branched alveolar ducts and numerous surrounding alveoli, and so in this study, we hypothesized that the particle deposition can be much influenced by the complex acinar geometry, and simulated the airflow and particle deposition (density = 1.0 g/cm(3), diameter = 1 and 3 μm) numerically in a pulmonary acinar model based on synchrotron micro-CT of the mammalian lung. We assumed that the fluid-structure interaction was neglected and that alveolar flow was induced by the expansion and contraction of the acinar model with the volume changing sinusoidally with time as the moving boundary conditions. The alveolar flow was dominated by radial flows, and a weak recirculating flow was observed at the proximal side of alveoli during the entire respiratory cycle, despite the maximum Reynolds number at the inlet being 0.029. Under zero gravity, the particle deposition rate after single breathing was less than 0.01, although the particles were transported deeply into the acinus after inspiration. Under a gravitational field, the deposition rate and map were influenced strongly by gravity orientation. In the case of a particle diameter of 1 μm, the rate increased dramatically and mostly non-deposited particles remained in the model, indicating that the rate would increase further after repeated breathing. At a particle diameter of 3 μm, the rate was 1.0 and all particles were deposited during single breathing. Our results show that the particle deposition rate in realistic pulmonary acinar model is higher than in an idealized model.


The antisecretory factor: synthesis and intracellular localisation in porcine tissues.
The antisecretory factor, AF, is a 41-kDa protein, cloned and sequenced from a human pituitary library. AF is a potent inhibitor of experimental intestinal hypersecretion in rats and pigs. An antiserum against the C-terminal of the truncated, recombinantly produced AF protein was raised in rabbits. The affinity-purified antiserum was used to study the expression of AF in mucosal membranes and in the pituitary gland of the pig; distinctly stained cells were found in lymphoid cells in the connective tissue of all parts of the gastrointestinal, respiratory and urinary tracts. Cytoplasmic AF was demonstrated in endocrine and epithelial cells in the pituitary gland. In situ hybridisation with a digoxigenin-labelled mRNA probe also demonstrated specific cytoplasmic staining in epithelial and lymphoid cells in all of these tissues. The cells stained by either method were similarly distributed topographically within the tissues. The results suggest that a specific defined cell population in these various tissues possesses the capability of both synthesising and storing the AF protein within the cellular cytoplasmic compartment.


Biogeography of soil archaea and bacteria along a steep precipitation gradient.
For centuries, biodiversity has spellbound biologists focusing mainly on macroorganism's diversity and almost neglecting the geographic mediated dynamics of microbial communities. We surveyed the diversity of soil bacteria and archaea along a steep precipitation gradient ranging from the Negev Desert in the south of Israel (<100 mm annual rain) to the Mediterranean forests in the north (>900 mm annual rain). Soil samples were retrieved from triplicate plots at five long-term ecological research stations, collected from two types of patches: plant interspaces and underneath the predominant perennial at each site. The molecular fingerprint of each soil sample was taken using terminal restriction length polymorphism of the 16S rRNA gene to evaluate the bacterial and archaeal community composition and diversity within and across sites. The difference in community compositions was not statistically significant within sites (P=0.33 and 0.77 for bacteria and archaea, respectively), but it differed profoundly by ecosystem type. These differences could largely be explained by the precipitation gradient combined with the vegetation cover: the archaeal and bacterial operational taxonomic units were unique to each climatic region, that is, arid, semiarid and Mediterranean (P=0.0001, for both domains), as well as patch type (P=0.009 and 0.02 for bacteria and archaea, respectively). Our results suggest that unlike macroorganisms that are more diverse in the Mediterranean ecosystems compared with the desert sites, archaeal and bacterial diversities are not constrained by precipitation. However, the community composition is unique to the climate and vegetation cover that delineates each ecosystem.


Associations Between Unhealthy Lifestyle Behaviors and Metabolic Syndrome by Gender in Young Adults.
Unhealthy lifestyle behaviors, such as smoking, drinking, betel-quid chewing, insufficient exercise, and inadequate sleep are significantly correlated with metabolic syndrome (MetS). To further understand this relationship, this study examined the main effect of unhealthy lifestyle behaviors and their interaction on MetS by gender in young adults. A cross-sectional study involving 694 young adults from a national survey was performed in which demographic characteristics, unhealthy lifestyle behaviors, anthropometric measurements, and blood chemistry panels were collected during face-to-face interviews. The prevalence of MetS among young adults was 17.4% and was greater in males than females (19.0% vs. 7.8%). The unhealthy lifestyle-behavior risk factors associated with MetS included smoking (odds ratio [ OR] = 4.53) and physical activity ( OR = 0.51) among males and betel-quid chewing ( OR = 8.90) and less sleep ( OR = 0.08) among females. Significant interaction effects were observed between the abovementioned behaviors and gender for the risk of developing MetS. These results can guide health-care providers in reducing MetS risk by encouraging young adult males to reduce or quit cigarette smoking and maintain optimum levels of physical activity and young adult females to quit chewing betel quid and obtain appropriate amounts of sleep.


Proinsulin in development: New roles for an ancient prohormone.
In postnatal organisms, insulin is well known as an essential anabolic hormone responsible for maintaining glucose homeostasis. Its biosynthesis by the pancreatic beta cell has been considered a model of tissue-specific gene expression. However, proinsulin mRNA and protein have been found in embryonic stages before the formation of the pancreatic primordium, and later, in extrapancreatic tissues including the nervous system. Phylogenetic studies have also confirmed that production of insulin-like peptides antecedes the morphogenesis of a pancreas, and that these peptides contribute to normal development. In recent years, other roles for insulin distinct from its metabolic function have emerged also in vertebrates. During embryonic development, insulin acts as a survival factor and is involved in early morphogenesis. These findings are consistent with the observation that, at these stages, the proinsulin gene product remains as the precursor form, proinsulin. Independent of its low metabolic activity, proinsulin stimulates proliferation in developing neuroretina, as well as cell survival and cardiogenesis in early embryos. Insulin/proinsulin levels are finely regulated during development, since an excess of the protein interferes with correct morphogenesis and is deleterious for the embryo. This fine-tuned regulation is achieved by the expression of alternative embryonic proinsulin transcripts that have diminished translational activity.


Single coronary artery with anomalous origin from the pulmonary trunk: congenital lack of coronary arteries originating from the aortic bulb.
A 23-year-old woman with an initial diagnosis of dilated cardiomyopathy for several years was referred to our center because of progressive congestive heart failure. Echocardiography showed a hypokinetic dilated left ventricle with globally impaired systolic function and an ejection fraction of 30%. We performed multislice cardiac computed tomography that revealed abnormal origin of the single coronary artery from the pulmonary trunk, lack of coronary arteries arising from the aorta, and abundant collateral flow from the bronchial artery to the anomalous coronary artery. This case report shows that cardiac computed tomography can be a valuable tool in the diagnosis of rare coronary anomalies.


Dynamics of chromosome number and genome size variation in a cytogenetically variable sedge (Carex scoparia var. scoparia, Cyperaceae).
High intraspecific cytogenetic variation in the sedge genus Carex (Cyperaceae) is hypothesized to be due to the "diffuse" or non-localized centromeres, which facilitate chromosome fission and fusion. If chromosome number changes are dominated by fission and fusion, then chromosome evolution will result primarily in changes in the potential for recombination among populations. Chromosome duplications, on the other hand, entail consequent opportunities for divergent evolution of paralogs. In this study, we evaluate whether genome size and chromosome number covary within species. We used flow cytometry to estimate genome sizes in Carex scoparia var. scoparia, sampling 99 plants (23 populations) in the Chicago region, and we used meiotic chromosome observations to document chromosome numbers and chromosome pairing relations. Chromosome numbers range from 2n = 62 to 2n = 68, and nuclear DNA 1C content from 0.342 to 0.361 pg DNA. Regressions of DNA content on chromosome number are nonsignificant for data analyzed by individual or population, and a regression model that excludes slope is favored over a model in which chromosome number predicts genome size. Chromosome rearrangements within cytogenetically variable Carex species are more likely a consequence of fission and fusion than of duplication and deletion. Moreover, neither genome size nor chromosome number is spatially autocorrelated, which suggests the potential for rapid chromosome evolution by fission and fusion at a relatively fine geographic scale (<350 km). These findings have important implications for ecological restoration and speciation within the largest angiosperm genus of the temperate zone.


Most human carcinomas of the exocrine pancreas contain mutant c-K-ras genes.
Using in vitro gene amplification by the polymerase chain reaction (PCR) and mutation detection by the RNAase A mismatch cleavage method, we have examined c-K-ras genes in human pancreatic carcinomas. We used frozen tumor specimens and single 5 micron sections from formalin-fixed, paraffin-embedded tumor tissue surgically removed or obtained at autopsy. Twenty-one out of 22 carcinomas of the exocrine pancreas contained c-K-ras genes with mutations at codon 12. In seven cases tested, the mutation was present in both primary tumors and their corresponding metastases. No mutations were detected in normal tissue from the same cancer patients or in five gall bladder carcinomas. We conclude from these results that c-K-ras somatic mutational activation is a critical event in the oncogenesis of most, if not all, human cancers of the exocrine pancreas.


Link between childhood asthma and mental health conditions.
Asthma and mental health conditions often coexist and studies support a link between the two disorders. Indeed, an increase in the incidence of depression and anxiety has been reported in children with asthma compared to those without asthma. Direction of causality in the relationship is unclear. Parental stress appears to be an important factor important in the development of infant wheezing. There is support for a working hypothesis, linking inner-city violence and the development of childhood asthma via pathways that include parental mental health conditions, parental nicotine addiction, environmental tobacco smoke, and Th2 skewing in infants. It is anticipated that a better understanding of the above relationships will lead to the development of new targeted treatment strategies for childhood asthma in the future.


Lanthanide fluorescence studies of transfer RNAf(met) conformation.
The possible difference in conformation between aminoacylated and deacylated tRNA is examined using the optical and photochemical properties of the 4-thiouridine residue of E coli tRNAf(Met). No differences were seen between fMet-tRNAf(Met) and tRNAf(Met) observing the native fluorescence of 4-thiouridine, energy transfer from 4-thiouridine to the bound lanthanide ions, Tb3+ or Eu3+, or the rates of the photochemical cross-linking reaction of 4-thiourdine. While these results do not necessarily mean that there is no conformational difference between the aminoacylated and deacylated species, they do restrict the possible nature and magnitude of any conformational difference between the two species. In addition, preliminary thermal denaturation studies of tRNAf(Met), monitoring 4-thiouridine emission and energy transfer to Tb3+, indicate an unexplained melting phenomenon near 25 degrees C in the presence of Mg2+.


[Zinc metabolism in duodenal ulcer].
Zinc concentrations were measured in blood and gastroduodenal mucosa of patients with duodenal ulcer in remission and exacerbation. These were found reduced in plasma but elevated in gastroduodenal mucosa. Healing of the ulcer lesion was associated with positive shifts in zinc metabolism which recovered normal values in ulcer remission. It is concluded that plasma and gastroduodenal levels of zinc reflect the stage of the pathological process in peptic ulcer.


Histamine poisoning on ingestion of tuna fish.
When tuberculosis patients on isoniazid eat certain varieties of fish they may develop a histamine reaction. The occurrence of this reaction in a mother and daughter on ingestion of tuna fish is reported. Two other members of the family who were on treatment for tuberculosis but had not taken isoniazid on the day of the episode were unaffected by the same meal.


Seizures as a Consequence of Hyperviscosity Syndrome in Two Dogs Naturally Infected with Leishmania infantum.
Serum hyperviscosity syndrome (HVS) was documented in two dogs with canine leishmaniasis (CanL) and seizures as the major clinical complaint. In both cases, laboratory abnormalities included mild non-regenerative anemia, thrombocytopenia, hypoalbuminemia, hyperproteinemia with monoclonal gammopathy, and marked serum hyperviscosity. CanL was diagnosed using cytology in one case and indirect immunofluorescence assay and conventional polymerase chain reaction in the second. Specific therapy with meglumine antimoniate and allopurinol(c) led to short-term remission in both dogs and normalization of serum viscosity. Although dogs rarely develop HVS, it should be suspected if hyperproteinemia and monoclonal gammopathy are present. Since CanL manifests with a variety of clinical presentations, including seizures resulting from HVS-induced central nervous system hypoxia, it should also be considered as a differential diagnosis in animals with seizures as a primary presenting sign.


Alternative treatment for allergy and asthma.
Treatment of asthma remains complex. Patients who are considering alternative and complementary treatments for asthma should have a good understanding of what the treatment entails, and whether it has proven ability to make an impact in the disease. One should remember, however, these treatments are made to complement most traditional therapies and not to replace them.


Centrosymmetric (Hdima)2[Ge5B3O15(OH)] and Noncentrosymmetric Na4Ga3B4O12(OH): Solvothermal/Surfactant-Thermal Synthesis of Open-Framework Borogermanate and Galloborate.
Under solvothermal/surfactant-thermal conditions, two new open-framework borogermanate and galloborate, centrosymmetric (Hdima)2[Ge5B3O15(OH)] (1; dima = dimethylamine) and noncentrosymmetric Na4Ga3B4O12(OH) (2), were obtained and characterized. Compound 1 contains an unusual basket-shaped Ge5B3O18(OH) cluster and displays a 3D open-framework layered structure. Compound 2 shows an interrupted 3,4-connected network constructed by alternately linked BO3 units and Ga3+ ions and displays weak second-harmonic-generation response.


A computational study on the role of noncovalent interactions in the stability of polymer/graphene nanocomposites.
Understanding the interaction between graphene and polymers is of essential interest when designing novel nanocomposites with reinforced mechanical and electrical properties. In this computational study, the interaction of pristine graphene (PG) and graphene oxide (GO) with a series of functional groups, representative of the functionalised buildings blocks occurring in different polymers, and attached to aliphatic and aromatic chains, is analyzed using dispersion-corrected semi-empirical methods (PM6-D3H4X) and density functional theory calculations with empirical dispersion corrections. Functional groups include alkyl, hydroxyl, aldehyde, carboxyl, amino and nitro groups, and the binding energies of these groups with graphene derivatives (PG and GO) are determined. Nitro- and carbonyl groups display stronger interactions in both aliphatic and aromatic chains. The importance of dispersion-type and non-covalent interactions (NCI) in general, which typically, double the interaction energies, is revealed. The results are interpreted in an extensive NCI analysis in order to characterize the different types of NCI, providing a better understanding of the nature of the interaction (π-π stacking, CH-π bonding, H-bonding and lone pair-π interaction) at stake. In order to highlight the influence of polymer structure/conformation on top of that of their functional groups, the binding of three polymers, polyethylene (PE), polystyrene (PS) and polyvinylidene fluoride (PVDF), on pristine graphene is also investigated. Our calculations indicate that, although all polymers exhibit evident attractive interactions with the graphene sheet, the overall interaction is strongly influenced by the specific polymer structure. Thus, three main conformations of PVDF (the so-called α, β and γ, ε conformations) are analyzed and we find that, although the α-conformer with a trans-gauche-trans-gauche (TGTG') conformation is the lowest energy conformer, the β-conformation of PVDF with the hydrogen atoms facing the graphene ("F-up") has the strongest interaction with the graphene surface among the polymers under consideration. Taken together, our computational approach sheds light on the character and importance of non-covalent graphene-polymer functional group interactions combined with the structural/conformational properties of the polymer, which are at stake in the design of novel nanocomposites with reinforced mechanical and electrical properties.


MAdCAM-1 expressed in chronic inflammatory liver disease supports mucosal lymphocyte adhesion to hepatic endothelium (MAdCAM-1 in chronic inflammatory liver disease).
Mucosal addressin cell adhesion molecule (MAdCAM-1) plays a pivotal role in T-lymphocyte homing to the gut. Given the strong association between the autoimmune liver diseases primary sclerosing cholangitis and autoimmune hepatitis and inflammatory bowel disease, we investigated the role of MAdCAM-1 in recruiting mucosal lymphocytes to the liver. MAdCAM-1 was strongly expressed on inflamed portal vein/sinusoidal endothelium in autoimmune mediated liver disease. In modified Stamper-Woodruff assays, MAdCAM-1 on hepatic vessels supported adhesion of alpha4beta7+ lymphocytes (i.e., gut-derived T cells) from patients with inflammatory bowel disease and primary sclerosing cholangitis. This adhesion was inhibited by pretreatment with blocking antibodies to MAdCAM-1, alpha4beta7, or the integrin alpha4 chain indicating that MAdCAM-1 in inflamed liver is functionally active. Circulating lymphocytes from patients with primary sclerosing cholangitis showed rolling adhesion on MAdCAM-1 transfectants in a flow-based adhesion assay that could be blocked by anti-MAdCAM-1 or anti-alpha4beta7 mAbs. These findings indicate that, under certain circumstances, vessels in the human liver support adhesion of alpha4beta7+ mucosal lymphocytes via binding to aberrantly expressed MAdCAM-1 on liver endothelium. This provides a mechanism to explain the hepatic recruitment of mucosal lymphocytes in inflammatory liver disease complicating inflammatory bowel disease.


[State of the art and therapeutic prospects in neuroectodermal tumours and other neuroendocrine pathologies].
The clinical and biological characteristics of neuroectodermal tumours (NETs) are such that their treatment is necessarily multidisciplinary. Surgery is the first therapeutic choice given that it is the only potentially curative treatment for this type of neoplasm. Medical treatment is mainly indicated in the treatment of metastatic disease and must be separated into three basic options: chemotherapy, immunotheraphy and hormone treatment. Owing to the low proliferative index generally found in NETs, chemotherapy is not very effective as a means of controlling tumour growth. Data in the literature on interferon suggest that it plays a limited role in the treatment of NETs, as do the preliminary results from studies on the association of interferon + chemotherapy. The introduction of somatostatin analogs in clinical practice represents an effective tool in the therapeutic strategy for NETs and has opened new possibilities for the management of other neoplasms. One particularly interesting aspect of the octreotide-mediated antitumour action concerns the blocking of tumour neo-angiogenesis. The majority of non-endocrine tumours also express specific somatostatin receptors and in theory it is possible to hypothesise an antiproliferative action also in tumours without these receptors mediated by the indirect antiproliferative effects of somatostatin.


Emergency access authorization for personally controlled online health care data.
Personally controlled health records (PCHR) systems have emerged to allow patients to control their own medical data. In a PCHR system, all the access privileges to a patient's data are granted by the patient. However, in many emergency cases, it is impossible for the patient to participate in access authorization on site when immediate medical treatment is needed. To solve the emergency access authorization problem in the absence of patients, we consider two cases: a) the requester is already in the PCHR system but has not obtained the access privilege of the patient's health records, and b) the requester does not even have an account in the PCHR system to submit its request. For each of the two cases, we present a method for emergency access authorization, utilizing the weighted voting and source authentication cryptographic techniques. Our methods provide an effective, secure and private solution for emergency access authorization, that makes the existing PCHR system frameworks more practical and thus improves the patients' experiences of health care when using PCHR systems. We have implemented a prototype system as a proof of concept.


Sensitized two-photon photochemical deprotection.
The photoremovable protecting group NPPoc has little sensitivity to two-photon excitation, limiting its use in applications requiring high spatial control of its photochemistry. In the presence of a triplet sensitizer with a large two-photon absorption cross-section, however, the two-photon uncaging action cross-section is improved to levels useful in a variety of applications.


The influence of valve physiology on outcome following aortic valvotomy for congenital bicuspid valve in children: 30-year results from a single institution.
Aortic valvotomy is widely used for the treatment of congenital aortic stenosis in children. We sought to evaluate whether the predominant post-valvotomy physiology, aortic insufficiency (AI) or aortic stenosis (AS) independently affected patient outcome. From 1972-2002, 57 children with congenital aortic stenosis underwent valvotomy. We divided age-matched patients with residual lesions based on their predominant pathology into three groups: Group I (n=14), patients with moderate AI; Group II (n=14), patients with moderate AS, and Group III (n=14), patients with combined AI and AS. Fifteen patients with severe AI or mild residual lesions following valvotomy were excluded from analysis. mean freedom from aortic valve replacement (AVR) was 11.2+/-1.7 years in Group I and 21.5+/-3.9 years in Group II, P=0.05. AVR was required in 11 patients (79%) in Group I vs. only 5 (36%) in Group II, P=0.05. Group III was intermediate, with 9 (64%) requiring AVR. At the time of AVR, patients with aortic stenosis had significantly higher fractional shortening % than those with insufficiency or combined lesions, (Group 1: 38.2+/-7.9 vs. Group II: 46.3+/-5.5 vs. Group III: 39.2+/-3.7, P=0.007). Patients in Group II also had less severely dilated ventricles (mm) than those in the other groups, (Group 1: 50.2+/-12.5 vs. Group II: 39.5+/-8.3 vs. Group III: 49.0+/-8.1, P=0.030). patients with predominant AI following valvotomy are more likely to need AVR sooner than those with residual stenosis without AI. Therefore, cautious use of repeat valvotomy using maneuvers to avoid AI (small balloons), may prolong freedom from aortic valve replacement in those patients with significant residual AS.


Dominant role of complement in the hyperacute xenograft rejection reaction.
Xenotransplantation in distantly related donor-recipient systems is rejected within minutes. According to present theories, hyperacute rejection is due to preformed antibodies. However, our results suggest that a nonimmunologic reaction plays a dominant role in the hyperacute rejection reaction. To analyze the hyperacute rejection reaction, a previously described model of isolated in vitro xenohemoperfusion was used in which rat kidneys were perfused with dog blood at constant pressure. Rejection criterion was cessation of xenograft perfusion flow rate with constant perfusion pressure and histologic findings of aggregation of thrombocytes and endothelial lesions. In our experimental approach, the donor kidney was perfused with separate cellular and humoral components of the recipient blood with redetection of the rejection activity in one of the recipient blood components. Each blood component was tested for preformed antibody before hemoperfusion. In control studies, xenoperfusion of rat kidneys with whole blood from the dog always resulted in hyperacute rejection. In contrast, allogenic perfusion with whole blood caused no rejection. In three groups, typical hyperacute rejection occurred. Perfusion with whole blood from newborn dogs; no preformed antibodies in vitro; perfusion with reactivated dog whole blood containing no preformed xenohemoagglutinating antibodies, which had been eliminated by adsorption, and perfusion with reactivated dog whole blood containing no preformed xenocomplement fixing antibodies also eliminated by adsorption, all resulted in hyperacute rejection. Whole blood from newborn dogs and reactivated, adsorbed antibody-free whole blood from dogs contained active complement. Perfusion of rat kidneys with heat decomplemented, antibody-containing or antibody-free dog blood showed no hyperacute rejection reaction. The addition of fresh complement to these last two groups resulted in typical hyperacute rejection.


[Repeated intravital morphological studies of the kidneys in patients with glomerulonephritis].
A clinicomorphological study was conducted over time in 62 patients with different morphological types of glomerulonephritis. An increase in vascular, interstitial and sclerotic changes was noted morphologically in most patients, the worst dynamics was observed in membranoproliferative glomerulonephritis. Disease progression was associated with 2 processes; sclerosis of all elements of the renal tissue or active inflammation.


[The influence of the thermal factor on the antigenic properties of skin].
Results of immunochemical studies of normal and thermally-treated human skin in vitro showed at least 2 of 4-5 organospecific dermal antigens to be thermostable-they withstood heating at 100 degrees C for 3 minutes; 2 or 3 antigens were thermolabile. The thermostable antigens possessed electrophoretic migration in the field of alpha1- and gamma-globulins. The burn eschar was found to retain one of the two thermostable oranospecific antigens together with the loss of thermolabile antigen.


How and what staff nurses learn about the medical devices they use in direct patient care.
Registered nurses (N = 323) working in a 500-bed tertiary care hospital in a large midwestern city were surveyed to determine what and how they initially learned about the medical devices they use, and the consequences of their use. The most frequently identified methods of initial learning were trial and error (taught self) and reading the user instruction manual. At least 90% of respondents indicated that when they first learned about the device they learned how to operate it and its purpose and function. Medical device use causes more than 75% of staff nurses to feel stressed; 11% had used a medical device that had harmed a patient.


Oxalic Acid Adsorption on Rutile: Experiments and Surface Complexation Modeling to 150 °C.
Here, we characterize oxalate adsorption by rutile in NaCl media (0.03 and 0.30 m) and between pH 3 and 10 over a wide temperature range which includes the near hydrothermal regime (10-150 °C). Oxalate adsorption increases with decreasing pH (as is typical for anion binding by metal oxides), but systematic trends with respect to ionic strength or temperature are absent. Surface complexation modeling (SCM) following the CD-MUSIC formalism, and as constrained by molecular modeling simulations and IR spectroscopic results from the literature, is used to interpret the adsorption data. The molecular modeling simulations, which include molecular dynamics simulations supported by free-energy and ab initio calculations, reveal that oxalate binding is outer-sphere, albeit via strong hydrogen bonds. Conversely, previous IR spectroscopic results conclude that various types of inner-sphere complexes often predominate. SCMs constrained by both the molecular modeling results and the IR spectroscopic data were developed, and both fit the adsorption data equally well. We conjecture that the discrepancy between the molecular simulation and IR spectroscopic results is due to the nature of the rutile surfaces investigated, that is, the perfect (110) crystal faces for the molecular simulations and various rutile powders for the IR spectroscopy studies. Although the (110) surface plane is most often dominant for rutile powders, a variety of steps, kinks, and other types of surface defects are also invariably present. Hence, we speculate that surface defect sites may be primarily responsible for inner-sphere oxalate adsorption, although further study is necessary to prove or disprove this hypothesis.


Women's knowledge and attitudes toward anal Pap testing.
The objectives of this study were to determine women's knowledge of human papillomavirus (HPV) and anal cancer and knowledge and attitudes toward the anal Pap test. A convenience sample of 370 women from the general population 21 years or older completed a 48-question preintervention survey; read an informational pamphlet about anal cancer, HPV, and anal Pap tests; and then completed a 21-question postintervention survey in Augusta, Atlanta, and Savannah, GA. The survey assessed their knowledge about anal cancer, HPV, and the anal Pap test and determined their attitudes toward the anal Pap test. Only preintervention results were considered in this article. Descriptive statistics were determined for all variables. Only 17.6% of women had previously heard of anal Pap tests, and the majority knew nothing (48.9%) or only a little (38.5%) about anal cancer. Yet, most women (78.6%) knew that anal Pap tests help to prevent anal cancer, and 86.2% knew that anal Pap tests are not only for people who have anal sex. Only a minority of women recognized known risk factors for anal cancer. Lack of knowledge about anal Pap tests (43.8%), pain or discomfort (41.3%), cost (24.0%), and embarrassment (21.2%) were the main reasons cited for not wanting an anal Pap test. Although most women had limited knowledge about anal cancer and anal Pap tests and few recognized known risk factors for anal cancer, women were receptive to screening. Further implementation of anal Pap testing for women may be improved by understanding women's limited knowledge and concerns.


Refinement of breast cancer risk prediction with concordant leading edge subsets from prognostic gene signatures.
Several prognostic signatures have been identified for breast cancer. However, these signatures vary extensively in their gene compositions, and the poor concordance of the risk groups defined by the prognostic signatures hinders their clinical applicability. Breast cancer risk prediction was refined with a novel approach to finding concordant genes from leading edge analysis of prognostic signatures. Each signature was split into two gene sets, which contained either up-regulated or down-regulated genes, and leading edge analysis was performed within each array study for all up-/down-regulated gene sets of the same signature from all training datasets. Consensus of leading edge subsets among all training microarrays was used to synthesize a predictive model, which was then tested in independent studies by partial least squares regression. Only a small portion of six prognostic signatures (Amsterdam, Rotterdam, Genomic Grade Index, Recurrence Score, and Hu306 and PAM50 of intrinsic subtypes) was significantly enriched in the leading edge analysis in five training datasets (n = 2,380), and that the concordant leading edge subsets (43 genes) could identify the core signature genes that account for the enrichment signals providing prognostic power across all assayed samples. The proposed concordant leading edge algorithm was able to discriminate high-risk from low-risk patients in terms of relapse-free or distant metastasis-free survival in all training samples (hazard ratios: 1.84-2.20) and in three out of four independent studies (hazard ratios: 3.91-8.31). In some studies, the concordant leading edge subset remained a significant prognostic factor independent of clinical ER, HER2, and lymph node status. The present study provides a statistical framework for identifying core consensus across microarray studies with leading edge analysis, and a breast cancer risk predictive model was established.


Diversity in Gold Finger Structure Elucidated by Traveling-Wave Ion Mobility Mass Spectrometry.
Traveling wave ion mobility (TWIM) mass spectrometry (MS) is a powerful method for the structural and conformational analysis of proteins and peptides, enabling the differentiation of isomeric peptides (or proteins) that have the same sequence but are modified at different residues. In this study, the TWIM-MS technique was used to separate isomeric AuI metallopeptide ions that were formed by ZnII displacement from the parent zinc fingers (ZFs). The synthetic gold finger peptides were derived from the C-terminus of the HIV nucleocapsid p7 protein (NCp7-F2) and finger 3 of the Sp1 transcription factor (Sp1-F3). TWIM-MS enabled the acquisition of distinct product ion spectra for each isomer, clearly indicating the binding sites for the major conformers in the presence of multiple coordination possibilities. Collision cross-section measurements showed that the aurated peptide has a slightly more compact structure than the parent zinc compound NCp7-F2, which showed only one conformation.


Structural Characterizations of the Fas Receptor and the Fas-Associated Protein with Death Domain Interactions.
The Fas receptor is a representative death receptor, and the Fas-associated protein with death domain (FADD) is a crucial adapter protein needed to support the Fas receptor's activity. The Fas-FADD interactions constitute an important signaling pathway that ultimately induces apoptosis or programmed cell death in biological systems. The interactions responsible for this cell-death process are governed by the binding process of the Fas ligand to the Fas, followed by the caspase cascade activation. Using a computational approach, the present communication explores certain essential structural aspects of the Fas-FADD death domains and their interfacial interactions.


Transcatheter arterial embolization for hemorrhage caused by injury of the hepatic artery.
The aims of the study were to compare (i) the effects of transcatheter arterial embolization on initial hemostasis and the control of rebleeding in the treatment of hemorrhage due to hepatic artery injury; and (ii) the outcomes of embolization by different locations. Subjects were 32 patients with suspected hepatic artery injury who were transferred to Chi-Mei Foundation Medical Center for hepatic angiography and embolization. The causes of arterial injury included liver trauma (n = 15) and iatrogenic injury (n = 17). The sites of embolization were classified into four groups: group 1 (n = 8) was classified as 'combined outlet, target and inlet control' with embolization of the vascular lesion (target) and hepatic artery distal (outlet) and proximal (inlet) to the vascular lesion simultaneously; group 2 (n = 11) as 'combined target and inlet control'; group 3 (n = 8) as 'combined outlet and inlet control'; group 4 (n = 5) as 'inlet control' only. Successful initial hemostasis was achieved in 30 of the 32 patients (93.8%), with two failures, both of which were caused by liver injury and occurred in subjects in group 4. Rebleeding was seen in three patients who had successful initial hemostasis: two of them in group 4 (66.7%) and one in group 1 (12.5%). All rebleedings were successfully managed by repeat embolization. Abscess formation was found in two group 1 patients, and both were successfully managed by percutaneous drainage. Transcatheter arterial embolization is an effective method for hemostasis in hepatic artery hemorrhage for both patients with liver trauma and patients with iatrogenic injuries to the hepatic artery. Based on this experience, embolization of the vascular lesion and/or the arterial lumen distal to the vascular lesion combined with inlet control is recommended for preventing recurrent hemorrhage, but studies with larger sample sizes will be required to validate this conclusion.


TGF-beta1 calcium signaling increases alpha5 integrin expression in osteoblasts.
TGF-beta1 is a potent osteoactive factor and exhibits a wide variety of effects on osteoblasts, most of which are mediated through receptor associated Smad proteins. We have recently reported a novel TGF-beta1 intracellular Ca2+ signaling pathway in osteoblasts, and found that this signaling is required for the TGF-beta1 mediated enhancement of osteoblast adhesion to substrate. Given that interaction between the extracellular matrix protein fibronectin and alpha5beta1 integrin on the cell surface is principally responsible for osteoblast substrate adhesion, we examined here whether the TGF-beta1 stimulated Ca2+ signal is involved in this pathway. Our results show that, in primary human osteoblasts, the TGF-beta1 induced intracellular Ca2+ signal is responsible, in part, for the stimulation of expression of alpha5 integrin, but not of beta1 integrin or fibronectin. Increased levels of alpha5 integrin protein and mRNA were seen as early as 12 h after TGF-beta1 treatment, but were inhibited by co-treatment of cells with nifedipine, a selective L-type Ca2+ channel blocker. TGF-beta1 treatment increased both fibronectin and beta1 integrin protein production within 48 h, in a manner unaffected by co-treatment with nifedipine. Immunofluorescence observations revealed that TGF-beta1 treatment resulted in increased alpha5 integrin staining, and more prominent alpha5 integrin clustering, with increased co-localization with the actin cytoskeleton, effects that were blocked by co-treatment with nifedipine. The TGF-beta1 induced intracellular Ca2+ signal in human osteoblasts is thus an important mechanistic step in the regulation of alpha5 integrin expression, later contributing to enhanced cell adhesion.


AIBN/NaBr-promoted aerobic oxidation of benzylic alcohols via a radical process.
An economic and practical AIBN-initiated aerobic oxidation system of benzylic alcohols, hetero aryl alcohols and allyl alcohols was developed for the first time. Moderate to excellent yields were obtained with a broad substrate scope. Moreover, a proposed mechanism of a radical process was assumed and confirmed by the key intermediate detected.


Enantiospecific tritium labeling of 28-homocastasterone.
A regiospecific and enantiospecific synthesis of tritium-labeled 28-homocastasterone is reported. Appropriate chlorocarbonate, efficiently synthesized from the starting 28-homocastasterone in an overall yield of 46%, undergoes catalytic tritium dechlorination by the T2 /Pd[0]/Et3 N system, providing 28-[3β-3 H]homocastasterone, in a good yield, radiochemical purity (>97%), and with a high specific activity (5.8 Ci/mmol).


Inactivation of Galpha(z) causes disassembly of the Golgi apparatus.
We showed previously that overexpression of the alpha subunit of G(z) or G(i2) suppresses nordihydroguaiaretic acid-induced Golgi disassembly. To determine whether the active form of Galpha is required to maintain the structure of the Golgi apparatus, we examined the effects of a series of Galpha GAPs, regulators of G protein signaling (RGS) proteins, on the Golgi structure. Expression of RGSZ1 or RGSZ2, both of which exhibit high selectivity for Galpha(z), markedly induced dispersal of the Golgi apparatus, whereas expression of RGS proteins that are rather selective for Galpha(q) or other Galpha(i) species did not. A mutated RGSZ1, which is deficient in the interaction with Galpha(z), did not induce Golgi disassembly. These results suggest that the active form of Galpha(z), but not Galpha(i2), is crucial for maintenance of the structure of the Golgi apparatus. Consistent with this idea, Golgi disruption also took place in cells transfected with a dominant-negative Galpha(z) mutant. Although previous studies showed that the expression of Galpha(z) is confined to neuronal cells and platelets, immunofluorescence and mRNA expression analyses revealed that it is also expressed, albeit at low levels, in non-neuronal cells, and is located in the Golgi apparatus. These results taken together suggest a general regulatory role for Galpha(z) in the control of the Golgi structure.


Musculoskeletal manifestations in inflammatory bowel disease.
Musculoskeletal manifestations are the most common extra-intestinal complication of inflammatory bowel disease (IBD). They are part of the clinical spectrum of spondylarthropathies and include different articular manifestations. In addition to axial symptoms, peripheral findings such as seronegative oligoarthritis, dactylitis, and enthesopathy commonly occur, sometimes representing the only manifestation. Wide ranges of prevalence have been reported, depending on the criteria used to define spondyloarthropathy and on the selection of patients. In an inceptional cohort of newly diagnosed IBD patients, we observed musculoskeletal manifestations in 30.7% of the patients. The clinician should, therefore, carefully evaluate any rheumatological findings in order to provide an accurate and early diagnosis, and to establish an adequate therapy. In this article, epidemiological, clinical, and diagnostic aspects are discussed. Furthermore, the contribution of intestinal bacteria and immunogenetic factors to the pathogenesis of arthritis is briefly reviewed. Finally, we summarize the available therapeutic options.


An update on Community Care of North Carolina's Medicare demonstrations.
To enhance the impact of Community Care of North Carolina (CCNC)'s population health initiatives, CCNC partnered with the US Centers for Medicare and Medicaid Services to bring persons who are dually eligible for both Medicaid and Medicare, as well as Medicare beneficiaries, into CCNC's system of medical homes and community-based care management supports.


A systematic review of long-acting β2-agonists versus higher doses of inhaled corticosteroids in asthma.
To compare the efficacy of inhaled corticosteroids (ICS) plus long-acting β2 agonist (LABA) versus higher doses of ICS in children/adolescents with uncontrolled persistent asthma. Randomized, prospective, controlled trials published January 1996 to January 2012 with a minimum of 4 weeks of LABA+ICS versus higher doses of ICS were retrieved through Medline, Embase, Central, and manufacturer's databases. The primary outcome was asthma exacerbations requiring systemic corticosteroids; secondary outcomes were the pulmonary function test (PEF), withdrawals during the treatment period, days without symptoms, use of rescue medication, and adverse events. Nine studies (n = 1641 patients) met criteria for inclusion (7 compared LABA+ICS versus double ICS doses and 2 LABA+ICS versus higher than double ICS doses). There was no statistically significant difference in the number of patients with asthma exacerbations requiring systemic corticosteroids between children receiving LABA+ICS and those receiving higher doses of ICS (odds ratio = 0.76; 95% confidence interval: 0.48-1.22, P = .25, I(2) = 16%). In the subgroup analysis, patients receiving LABA+ICS showed a decreased risk of asthma exacerbations compared with higher than twice ICS doses (odds ratio = 0.48; 95% confidence interval: 0.28-0.82, P = .007, I(2)= 0). Children treated with LABA+ICS had significantly higher PEF, less use of rescue medication, and higher short-term growth than those on higher ICS doses. There were no other significant differences in adverse events. There were no statistically significant group differences between ICS+LABA and double doses of ICS in reducing the incidence of asthma exacerbations but it did decrease the risk comparing to higher than double doses of ICS.


The effects of direct and microsomal activated aflatoxin B1 on chicken peritoneal macrophages in vitro.
Sephadex-elicited peritoneal exudate cells were cultured on glass coverslips in order to determine the effects of aflatoxin B1 (AFB1) on chicken macrophages. Adherent macrophage monolayers were exposed for 1 h to 5, 10, and 20 micrograms ml-1 of AFB1, directly or to 0.01, 0.1, 0.5, 1, and 5 micrograms ml-1 of AFB1 in the presence of a chicken microsomal mixed function oxidase system (MFO). After exposure, the macrophage cultures were washed and allowed to recover for 2 h in fresh culture medium. Parameters measured at 2 h post recovery period were the substrate adherence potential, morphological alterations, phagocytic ability, and number of sheep red blood cells (SRBC) internalized per phagocytic macrophage. Direct in vitro exposure to AFB1 resulted in a dose-dependent decrease in macrophage adherence potential, and an increase in cell damage as determined by nuclear disintegration and cytoplasmic blebbing, but no detrimental effects were observed on percent phagocytic cells or the number of internalized SRBC. However, significant reductions in adherence potential, increased morphological alterations, and reduced phagocytosis and internalization of SRBC were observed when MFOs were added to cultures treated with much lower doses of AFB1. Addition of piperonyl butoxide (a P-450 inhibitor) abrogated AFB1-MFO induced alterations. This study suggests that microsomal activated AFB1 causes significant alterations in chicken macrophage functions.


Resilience and developmental psychopathology.
Humans vary to a great extent in their ability to adapt to adverse experiences. Resilience reflects the positive end of this spectrum of adaptation and maladaptation in response to risk exposure. Some individuals, despite being faced with the most pernicious of adversities, manage to avoid psychologic collapse and to maintain healthy adjustment. For decades, researchers and clinicians have searched for the correlates and causes of resilience, and several comprehensive reviews of these efforts are available. This article provides an overview of resilience research and selectively summarizes recent advances in the field, with a particular focus on a developmental psychopathology perspective. This article highlights some of the challenges to resilience research and uses the example of maltreatment to illustrate some of these issues.


The influence of inoculum composition on selected bioactive and nutritional parameters of grass pea tempeh obtained by mixed-culture fermentation with Rhizopus oligosporus and Aspergillus oryzae strains.
Tempeh is a popular Indonesian product obtained from legume seeds by solid-state fermentation with Rhizopus sp. The aim of this research was to study the effect of simultaneous mixed-culture fermentation of grass pea seeds on selected parameters of products as compared to traditional tempeh. The inoculum contained different ratios of Rhizopus oligosporus and Aspergillus oryzae spores. The simultaneous fermentation of grass pea seeds with inoculum consisting of 1.2 × 10(6) R. oligosporus and 0.6 × 10(6) A. oryzae spores (per 60 g of seeds) resulted in a product of improved quality, as compared with traditionally made tempeh (obtained after inoculation with 1.2 × 10(6) R. oligosporus spores), at the same fermentation time. This product had radical scavenging ability 70% higher than the one obtained with pure R. oligosporus culture and contained 2.23 g/kg dm of soluble phenols. The thiamin and riboflavin levels were above three (340 µg/g dm) and two (50.50 µg/g dm) folds higher than in traditionally made tempeh, respectively. The product had 65% in vitro bioavailability of proteins and 33% in vitro bioavailability of sugars. It also contained 40% less 3-N-oxalyl-L-2, 3-diaminopropionic acid (0.074 g/kg dm), as compared to traditional tempeh.


Long-term impact of oral vancomycin, ciprofloxacin and metronidazole on the gut microbiota in healthy humans.
The impact of combination antibiotic therapy on the composition of the intestinal microbiota remains ill-defined. We aimed to assess the effect of a 1 week antibiotic regimen on the intestinal microbiota of healthy humans for a period of up to 31 months. Thirteen healthy adult men received either no treatment or oral broad-spectrum antibiotics (ciprofloxacin, vancomycin and metronidazole) for 7 days. At four timepoints (prior to treatment, on day 9, day 49 and 8-31 months later) faecal samples were collected and analysed using 16S RNA gene sequencing. The short-term impact of broad-spectrum antibiotics on the gut microbiota was profound, with a loss of diversity and drastic shifts in community composition. In addition, antibiotics significantly reduced the abundance of bacterial taxa with important metabolic functions, such as the production of butyrate. The microbiota showed a remarkable return towards baseline after 8-31 months, but community composition often remained altered from its initial state. These findings suggest that combined treatment with vancomycin, ciprofloxacin and metronidazole has a profound and long-lasting effect on microbiota composition, the consequences of which remain largely unknown.


Mesenchymal hamartoma of the bilateral chest wall in neonates.
A mesenchymal hamartoma of the chest wall is a rare benign tumor. Each case has a different clinical course as well as different radiological imaging findings, and various histopathological diagnoses. In addition, mesenchymal hamartoma is sometimes mistaken for a malignant tumor. This report presents a neonatal case of mesenchymal hamartoma of the bilateral chest wall.


Toxicity of antineoplastic drug combinations in vitrectomy infusion fluid.
We evaluated a combination of various antineoplastic drugs used in vitrectomy infusion fluid for toxicity. A combination of 250 micrograms/ml of 5-fluorouracil with each of the following agents, 8.0 micrograms/ml of thiotepa or 40 micrograms/ml of etoposide, or 0.1 micrograms/ml doxorubicin, or 0.1 microgram/ml vincristine was tolerated well in the rabbit eyes.


Widely tunable, efficient on-chip single photon sources at telecommunication wavelengths.
We demonstrate tunable on-chip single photon sources using the Stark tuning of single quantum dot (QD) excitonic transitions in short photonic crystal waveguides (PhC WGs). The emission of single QDs can be tuned in real-time by 9 nm with an applied bias voltage less than 2V. Due to a reshaped density of optical modes in the PhC WG, a large coupling efficiency β ≥ 65%to the waveguide mode is maintained across a wavelength range of 5 nm. When the QD is resonant with the Fabry-Perot mode of the PhC WG, a strong enhancement of spontaneous emission is observed leading to a maximum coupling efficiency β = 88%. These results represent an important step towards the scalable integration of single photon sources in quantum photonic integrated circuits.


Analysis of autonomic modulation of heart rate in patients with Parkinson's disease and elderly individuals submitted to game therapy training.
Elderly patients and individuals with Parkinson's disease have a reduction in autonomic heart rate modulation, which may influence the survival of these patients, and rehabilitation can minimize this event. We tested the hypothesis that rehabilitation protocol with game console would influence the cardiac autonomic modulation of patients with Parkinson's Disease. Eight-seven volunteers were divided into two groups, control (n = 45) and Parkinson's (n = 42), they completed the study 40 volunteers in the control group (CG) and 31 patients in the Parkinson group (PG), and subjected to 24 sessions of game therapy physiotherapy, thrice a week. Analysis of autonomic HR modulation was conducted before and after the rehabilitation program using a Polar RS800CX HR sensor. For the analysis of heart rate variability the data were transferred to the Kubios HRV 2.2 program. Statistical analysis was performed in the Biostat 5.2 program, the comparison of the data by ANOVA followed by Tukey test, and the general characteristics by the chi-square test. The critical value for rejecting the null hypothesis was set at P < 0.05. HR variability in patients with PD exhibited higher influence on the sympathetic nervous system before protocol implementation and, following the protocol, patients did not attain the normality values of the control group, exhibiting a discreet improvement and maintenance of autonomic modulation of HR values. Subjects with PD exhibit less autonomic modulation of HR and the rehabilitation protocol with game therapy improved autonomic modulation of HR. Geriatr Gerontol Int 2018; 18: 20-25.


A SINE of restricted gene flow across the Alpine Fault: phylogeography of the New Zealand common skink (Oligosoma nigriplantare polychroma).
New Zealand has experienced a complex climatic and geological history since the Pliocene. Thus, identifying the processes most important in having driven the evolution of New Zealand's biota has proven difficult. Here we examine the phylogeography of the New Zealand common skink (Oligosoma nigriplantare polychroma) which is distributed throughout much of New Zealand and crosses many putative biogeographical boundaries. Using mitochondrial DNA sequence data, we revealed five geographically distinct lineages that are highly differentiated (pairwise Phi(ST) 0.54-0.80). The phylogeographical pattern and inferred age of the lineages suggests Pliocene mountain building along active fault lines promoted their divergence 3.98-5.45 million years ago. A short interspersed nuclear element (SINE) polymorphism in the myosin gene intron (MYH-2) confirmed a pattern of restricted gene flow between lineages on either side of the mountain ranges associated with the Alpine Fault that runs southwest to northeast across the South Island of New Zealand. An analysis of molecular variance confirmed that approximately 40% of the genetic differentiation in O. n. polychroma is distributed across this major fault line. The straits between the main islands of New Zealand accounted for much less of the variation found within O. n. polychroma, most likely due to the repeated existence of landbridges between islands during periods of the Pleistocene that allowed migration. Overall, our findings reveal the relative roles of different climatic and geological processes, and in particular, demonstrate the importance of the Alpine Fault in the evolution of New Zealand's biota.


Vitellogenin and vitellogenin receptor gene expression profiles in Spodoptera exigua are related to host plant suitability.
The beet armyworm Spodoptera exigua, a worldwide phytophagous pest, causes considerable economic agricultural losses. Understanding the relationship between its fecundity and the host plant is a basic and important component of early forecasting of beet armyworm outbreaks. However, little is known about the molecular mechanism by which distinct hosts affect S. exigua fecundity. In this study, key life-history parameters of S. exigua reared on distinct hosts were investigated; the host plants could be ranked as lettuce > shallot > tomato > celery in their order of suitability. Full-length S. exigua vitellogenin receptor (SeVgR) cDNA was cloned, and sex-, stage- and tissue-specific expression characteristics were assessed. Spodoptera exigua vitellogenin (SeVg) and SeVgR expression levels were markedly modulated by host nutrients (P < 0.05). SeVg and SeVgR expression levels were significantly higher in S. exigua reared on lettuce, the most preferred and most nutritive host, than in those reared on tomato and celery. Interestingly, significant linear regression correlations were found between SeVg and SeVgR expression levels and key S. exigua life-history parameters, especially life span, pupa weight, and female fecundity (P < 0.01). Host plant type and suitability could affect the expression pattern of SeVg and SeVgR, which influenced S. exigua fecundity. Vg and VgR have the potential to be used as molecular markers of S. exigua fecundity and for forecasting outbreaks of S. exigua on different hosts. © 2017 Society of Chemical Industry.


Correlation between morphological and functional retinal impairment in multiple sclerosis patients.
To assess whether a correlation exists between optic nerve fiber layer (NFL) thickness and the retinal or visual pathway function in multiple sclerosis (MS) patients previously affected by optic neuritis. Fourteen patients with a diagnosis of definite MS were examined. All had been affected by optic neuritis (MSON) with complete recovery of visual acuity (14 eyes included in study). These were compared with 14 eyes from 14 age-matched control subjects. NFL thickness was measured by optical coherence tomography (OCT). Three different measurements in each quadrant (superior, inferior, nasal, and temporal) were taken and averaged. The data in all quadrants (12 values averaged) were identified as NFL Overall, whereas the data obtained in the temporal quadrant only (3 values averaged) were identified as NFL Temporal. Retinal and visual pathway function was assessed by simultaneously recording pattern electroretinograms (PERGs) and visual evoked potentials (VEPs) using high-contrast (80%) checkerboard stimuli subtending 15 minutes and 60 minutes of the visual arc (min arc) and reversed at the rate of two reversals per second. In MSON eyes there was a significant (P < 0.01) reduction in NFL thickness in both NFL Overall and NFL Temporal evaluations compared with the values observed in control eyes. PERG, (15-min arc checks) and VEP (15-min arc and 60-min arc checks), showed a significant (P < 0.01) delay in latency and reduction in amplitude. NFL Overall and NFL Temporal values were significantly correlated (P < 0.01) to the PERG P50 latency and P50 to N95 amplitude recorded with 15-min arc checks. No correlations (P > 0.01) between NFL values and the other electrophysiological data (PERG recorded with 60-min arc checks and VEP recorded with 15-min arc and 60-min arc checks) were found. There is a correlation between PERG changes and NFL thickness in MS patients previously affected by optic neuritis, but there is no correlation between VEP changes and NFL thickness.


Protein changes in macrophages induced by plasma from rats exposed to 35 GHz millimeter waves.
A macrophage assay and proteomic screening were used to investigate the biological activity of soluble factors in the plasma of millimeter wave-exposed rats. NR8383 rat macrophages were incubated for 24 h with 10% plasma from male Sprague-Dawley rats that had been exposed to sham conditions, or exposed to 42 °C environmental heat or 35 GHz millimeter waves at 75 mW/cm² until core temperature reached 41.0 °C. Two-dimensional polyacrylamide gel electrophoresis, image analysis, and Western blotting were used to analyze approximately 600 protein spots in the cell lysates for changes in protein abundance and levels of 3-nitrotyrosine, a marker of macrophage stimulation. Proteins of interest were identified using peptide mass fingerprinting. Compared to plasma from sham-exposed rats, plasma from environmental heat- or millimeter wave-exposed rats increased the expression of 11 proteins, and levels of 3-nitrotyrosine in seven proteins, in the NR8383 cells. These altered proteins are associated with inflammation, oxidative stress, and energy metabolism. Findings of this study indicate both environmental heat and 35 GHz millimeter wave exposure elicit the release of macrophage-activating mediators into the plasma of rats.