Effects of the Chiral Fungicides Metalaxyl and Metalaxyl-M on the Earthworm Eisenia fetida as Determined by ¹H-NMR-Based Untargeted Metabolomics.
Although metalaxyl and metalaxyl-M are widely used fungicides, very little is known about their subacute and enantiospecific effects on the earthworm metabolome. In this study, Eisenia fetida were exposed to metalaxyl and metalaxyl-M at three concentrations (0.5, 5 and 50 mg/kg) for seven days. ¹H nuclear magnetic resonance (¹H-NMR)-based untargeted metabolomics showed that metalaxyl and metalaxyl-M exposure disturbed earthworms' metabolism at all three concentrations. Endogenous metabolites, such as succinate, arginine, aspartate, urea, asparagine, alanine, trimethylamine, taurine, cysteine, serine, threonine, histidine, lysine, glucose, choline, carnitine, citric acid, alpha-ketoisovaleric acid, fumaric acid and so on, were significantly changed. These results indicate that metalaxyl and metalaxyl-M produce different, enantiospecific disturbances in the earthworm metabolism, particularly in the tricarboxylic acid (TCA) and urea cycles. The application of untargeted metabolomics thus provides more information for evaluating the toxic risks of metalaxyl and metalaxyl-M.


Layer-by-layer assembly of titania nanoparticles based ionic networks.
Recently nanoparticles ionic networks were reported in the frame of the remarkable development of new inorganic-organic hybrid materials based on nanoparticles assembly. In this article a layer-by-layer deposition method for the formation of imidazolium-based assemblies of photocatalytic titania nanoparticles is presented. This provides a new route for the controlled processing of this promising class of materials.


[The influence of osteotomy technique on distraction osteogenesis].
The authors reviewed the clinical results of leg lengthening by distraction osteogenesis, where two different osteotomy techniques were used: classical corticotomy according to Ilizarov or osteoclasis. Evaluation of results of 64 patients were bases on orthopedic examination and detailed X-ray analysis which included criteria assessing osseous regeneration rate. In those cases where osteoclasis was performed bone formation in the distraction gap was faster than in after osteotomy. An accelerated rate of regenerate formation, as well as a more active regenerate remodelling was observed. This allowed to shorten the time of external fixator application and an earlier rehabilitation.


Blocking of negative charged carboxyl groups converts Naja atra neurotoxin to cardiotoxin-like protein.
Naja atra cobrotoxin and cardiotoxin 3 (CTX3) exhibit neurotoxicity and cytotoxicity, respectively. In the present study, we aimed to investigate whether the carboxyl groups of cobrotoxin play a role in structural constraints, thereby preventing cobrotoxin from exhibiting cytotoxic activity. Six of the seven carboxyl groups in cobrotoxin were conjugated with semicarbazide. Measurement of circular dichroism spectra and Trp fluorescence quenching showed that the gross conformation of semicarbazide-modified cobrotoxin (SEM-cobrotoxin) and cobrotoxin differed. In sharp contrast to cobrotoxin, SEM-cobrotoxin demonstrated membrane-damaging activity and cytotoxicity, which are feature more characteristic of CTX3. Furthermore, both SEM-cobrotoxin and CTX3 induced cell death through AMPK activation. Analyses of the interaction between polydiacetylene/lipid vesicles and fluorescence-labeled lipids revealed that SEM-cobrotoxin and cobrotoxin adopted different membrane-bound states. The structural characteristics of SEM-cobrotoxin were similar to those of CTX3, including trifluoroethanol (TFE)-induced structural transformation and membrane binding-induced conformational change. Conversely, cobrotoxin was insensitive to the TFE-induced effect. Collectively, the data of this study indicate that blocking negatively charged residues confers cobrotoxin with membrane-damaging activity and cytotoxicity. The findings also suggest that the structural constraints imposed by carboxyl groups control the functional properties of snake venom α-neurotoxins during the divergent evolution of snake venom neurotoxins and cardiotoxins.


Effects of periadolescent fluoxetine and paroxetine on elevated plus-maze, acoustic startle, and swimming immobility in rats while on and off-drug.
Whether selective serotonin reuptake inhibitors (SSRIs) exposure during adolescent brain development causes lasting effects remains unresolved. Assess the effects of fluoxetine and paroxetine 60 days after adolescent exposure compared with when on-drug. Male Sprague-Dawley littermates (41 litters) were gavaged on postnatal days 33-53 with fluoxetine (3 or 10 mg/kg/day), paroxetine (3, 10 or, 17 mg/kg/day), or water; half were tested while on-drug (21 litters) and half after 60 days off-drug (20 litters). The highest dose of the drugs reduced body weight gain during treatment that rebounded 1 week post-treatment. On-drug, no significant group differences were found on elevated plus maze time-in-open, zone entries, or latency to first open entry; however, the high dose of paroxetine significantly reduced head-dips (N=20/group). No significant effects were found on-drug for acoustic startle response/prepulse inhibition (ASR/PPI) although a trend (p<0.10) was seen, which after combining dose levels, showed a significant increase in ASR amplitude for both fluoxetine and paroxetine (N=20-21/group). No differences on immobility time were seen in the Porsolt forced swim test or in plasma corticosterone at the end of forced swim (N-19-21/group). Off-drug, no effects were seen in the elevated plus maze (N=16/group), ASR/PPI (N=20/group), forced swim (N=19-20/group), or plasma corticosterone (N=19/group). At the doses tested, fluoxetine and paroxetine induced minor effects with drug on-board but no residual, long-term adverse effects in rats 60 days after drug discontinuation. The data provide no evidence that fluoxetine or paroxetine have long-term adverse effects on the behaviors measured here after adolescent to young adult exposure.


Measured effect of some socio-demographic factors on depression among breast cancer patients receiving chemotherapy in Lagos State University Teaching Hospital (LASUTH).
Breast cancer is a disease predominantly found amongst women. It is a disease which threatens an organ that is intimately associated with a woman's self image, sexuality, as well as her reproductive and nurturing capacity. These threats have serious psychological implications for women living with breast cancer. To examine the pattern and predictors of depressive symptoms among breast cancer patients receiving chemotherapy in the Lagos State University Teaching Hospital (LASUTH). Ethical approval was obtained for an ongoing multi-centre study. The data used in this study are pre-test scores from breast cancer patients in the Lagos State University Teaching Hospital. The 21-item Becks Depression Inventory II (BDI-II) was administered on 33 purposively sampled breast cancer patients who read and signed informed consent forms before taking part in the study. Analysis of data using simple percentages showed that the 33 participants indicated varying degree of depressive symptoms: 13 (39.4%) of the respondents had minimal depression, 12 (36.4%) of them had mild depression, 3 (9.1%) had moderate depression, and 5 (15.2%) had severe depression. The average BDI-II score yielded 16.09 indicating mild depression. Multiple regression analysis results showed that being informed about breast cancer, average monthly income, cancer stage and educational level significantly predicted participants' level of depression. This study confirmed the presence of depressive symptoms in cancer patients in Nigeria. It was recommended that intervention programs to help reduce these depressive symptoms be developed.


Acquired resistance to activated protein C (aAPCR) in multiple myeloma is a transitory abnormality associated with an increased risk of venous thromboembolism.
Acquired activated protein C resistance (aAPCR), not associated with factor V Leiden, has been described in cancer patients with an increased risk of venous thromboembolism (VTE). APCR was determined in 1178 myeloma patients using an activated partial thromboplastin time-based resistance assay in the presence of excess of factor V-deficient plasma; polymerase chain reaction amplification of genomic DNA was used to detect factor V Leiden mutation. A total of 109 patients were found to have abnormal APCR and one-third of them were carriers for the mutation. With a median follow-up of 40 months, the presence of aAPCR was associated with a significantly increased risk of thrombosis (P < or = 0.001). APCR was measured again after treatment in 31 patients with abnormal baseline values and had normalised in 30 of them. This study indicates that aAPCR is the most common single transitory baseline coagulation abnormality associated with VTE in myeloma patients.


Effect of dietary antioxidant supplementation on the oxidative status of plasma in broilers.
In this study, the effect of dietary antioxidants on the plasma oxidative status of growing birds fed a diet rich in polyunsaturated fatty acids was investigated. One-day-old broilers were fed for 42 days a diet containing 4% linseed oil and supplemented with single plant extracts rich in antioxidants (natural tocopherols, rosemary, grape seed, green tea, tomato) or a combination of some of these plant extracts, in two different total doses (100 and 200 mg product/kg feed). A diet with synthetic antioxidants with and without α-tocopheryl acetate (200 mg/kg feed) were also included. The plasma oxidative status was evaluated measuring the ferric reducing ability of plasma (FRAP), the superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activity. Lipid peroxidation was measured by thiobarbituric acid-reactive substances (TBARS). No significant effect of the dietary treatments was observed for FRAP as well as for TBARS. However, diet affected GSH-Px activity (p = 0.002) and a trend for an effect on SOD activity was observed (p=0.084). A higher GSH-Px activity was found for 200 mg/kg tomato extract and natural α-tocopherol in relation to the corresponding 100 mg/kg treatment, and the lowest GSH-Px activity was measured for the synthetic antioxidants treatment. The lowest and highest SOD activity were found for the 200. and 100 mg/kg treatment with tomato extract respectively. In conclusion, the oxidative status and lipid oxidation of plasma in broilers was not affected by feeding natural antioxidant extracts at the doses in the present study, but some changes in antioxidant enzyme activities were observed, of which the implication remains to be elucidated.


Effects of Bacillus amyloliquefaciens LFB112 on Growth Performance, Carcass Traits, Immune, and Serum Biochemical Response in Broiler Chickens.
This study aimed to investigate the effects of Bacillus amyloliquefaciens LFB112 on the growth performance, carcass traits, immune response, and serum biochemical parameters of broiler chickens. A total of 396 1 day old, mixed-sex commercial Ross 308 broilers with similar body weights were allotted into six treatment groups. The assigned groups were the CON group (basal diet with no supplement), AB (antibiotics) group (basal diet + 150 mg of aureomycin/kg), C+M group (basal diet + 5 × 108 CFU/kg B. amyloliquefaciens LFB112 powder with vegetative cells + metabolites), C group (basal diet + 5 × 108 CFU/kg B. amyloliquefaciens LFB112 vegetative cell powder with removed metabolites), M group (basal diet + 5 × 108 CFU/kg B. amyloliquefaciens LFB112 metabolite powder with removed vegetative cells), and CICC group (basal diet + 5 × 108 CFU/kg Bacillus subtilis CICC 20179). Results indicated that chickens in the C+M, C, and M groups had higher body weight (BW) and average daily gain (ADG) (p < 0.05) and lower feed conversion ratio (FCR) (p = 0.02) compared to the CON group. The C+M group showed the lowest abdominal fat rate compared to those in the CON, AB, and CICC groups (p < 0.05). Compared to the CON group, serum IgA and IgG levels in the C+M, C, and M groups significantly increased while declining in the AB group (p < 0.05). B. amyloliquefaciens LFB112 supplementation significantly reduced the serum triglyceride, cholesterol, urea, and creatinine levels, while increasing the serum glucose and total protein (p < 0.05). In conclusion, B. amyloliquefaciens LFB112 significantly improved the growth performance, carcass traits, immunity, and blood chemical indices of broiler chickens and may be used as an efficient broiler feed supplement.


Effect of adrenal blocking chemicals on the responses of chickens and turkeys to environmental stressors and ACTH.
An adrenal blocker, 1,1dichloro-2,2-bis/p-chlorophenyl/ethane, was most effective when given intramuscularly, at a dose rate of 16 or 14 mg/kg of body weight, the technical or reagent chemical, respectively (P<0.001). The optimal dose for meryrapone was 500 mg/kg feed. Following exposure to a variety of Stressors treated chickens and turkeys had heterophil/lymphocyte ratios which were lower than those of the uninjected controls. The optimal doses were effective over a wide range of body weights (0.35 to 5.2 kg). Blocking began within 12 h after injection and lasted for at least 77 days. Repeated doses were not additive. Blockers did not suppress body weight gain. The magnitude of the blocking effect increased with increasing H/L ratios among the controls and was ineffective in unstressed chickens.


Unmanaged Pharmacogenomic and Drug Interaction Risk Associations with Hospital Length of Stay among Medicare Advantage Members with COVID-19: A Retrospective Cohort Study.
Unmanaged pharmacogenomic and drug interaction risk can lengthen hospitalization and may have influenced the severe health outcomes seen in some COVID-19 patients. To determine if unmanaged pharmacogenomic and drug interaction risks were associated with longer lengths of stay (LOS) among patients hospitalized with COVID-19, we retrospectively reviewed medical and pharmacy claims from 6025 Medicare Advantage members hospitalized with COVID-19. Patients with a moderate or high pharmacogenetic interaction probability (PIP), which indicates the likelihood that testing would identify one or more clinically actionable gene-drug or gene-drug-drug interactions, were hospitalized for 9% (CI: 4-15%; p < 0.001) and 16% longer (CI: 8-24%; p < 0.001), respectively, compared to those with low PIP. Risk adjustment factor (RAF) score, a commonly used measure of disease burden, was not associated with LOS. High PIP was significantly associated with 12-22% longer LOS compared to low PIP in patients with hypertension, hyperlipidemia, diabetes, or chronic obstructive pulmonary disease (COPD). A greater drug-drug interaction risk was associated with 10% longer LOS among patients with two or three chronic conditions. Thus, unmanaged pharmacogenomic risk was associated with longer LOS in these patients and managing this risk has the potential to reduce LOS in severely ill patients, especially those with chronic conditions.


Learning speed is affected by personality and reproductive investment in a songbird.
Individuals from different taxa, including songbirds, differ consistently in behaviour and personality when facing different situations. Although our understanding of animal behaviour has increased, knowledge about between-individual differences in cognitive abilities is still limited. By using an experimental approach and a free-living songbird (Parus major) as a model, we attempted to understand between-individual differences in habituation to playbacks (as a proxy of learning speed), by investigating the role of personality, age and reproductive investment (clutch size). Pre-breeding males were tested for exploration (a proxy of personality) in standardized conditions. In addition, the same individuals were exposed to three playbacks in the field during incubation. Birds significantly moved less, stayed further away and overlapped less the playback with successive playback stimulation. While a decrease in the locomotor behaviour can be explained by personality, differences in habituation of overlapping were predicted by both reproductive investment and personality. Fast explorers habituated less. Moreover, males paired to females with larger clutches did not vary the intensity of overlapping. Since habituation requires information for recognition of non-threatening signals, personality may bias information gathering. While fast explorers may collect less information from the environment, slow explorers (reactive birds) seem to pay attention to environmental clues and collect detailed information. We provided evidence that the rate of habituation of behavioural responses, a proxy of cognitive abilities, may be affected by different factors and in a complex way.


Didanosine once daily: an overview.
The current focus on simplifying treatment regimens for patients with human immunodeficiency virus (HIV) infection has contributed to the interest in once-daily therapy. The triphosphate of didanosine (2',3'-dideoxyinosine or DDI) has a long intracellular half-life, which supports the use of didanosine in a once-daily dosing schedule. Early clinical studies found that changes in surrogate markers were similar whether didanosine was dosed once or twice daily, while toxic effects occurred less frequently with once-daily dosing. Didanosine once-a-day used in combination with other drugs has also been studied, and results of some of these trials are summarized in this paper.


Locking mechanism failure in the Harris-Galante porous acetabular component associated with recurrent hip dislocation.
In this review of longitudinal studies of the Harris-Galante porous acetabular component, 20% of all revisions were caused by failure of the polyethylene liner locking mechanism. We report 2 cases of locking mechanism failure in the Harris-Galante porous acetabular component presenting with recurrent dislocation. Broken tines from the acetabular locking mechanism were found embedded into the polyethylene liners in both cases. In a 79-year-old woman with recurrent dislocation, the polyethylene liner and femoral head were replaced, and the acetabular component was revised. In a 74-year-old man with chronic recurrent dislocation, the polyethylene liner and femoral head were replaced, but the acetabular component was preserved. Appropriate treatment for locking mechanism failure with a well-fixed acetabular component depends on many factors, and further long-term data are needed.


Eosinophilic conjunctivitis, herpes virus and mast cell tumor of the third eyelid in a cat.
A 3-year-old Himalayan cat was diagnosed with concurrent eosinophilic conjunctivitis, herpes virus, and a conjunctival mast cell tumor. Eosinophilic conjunctivitis was verified via cytology from a conjunctival scraping, which revealed 50% eosinophils and 50% neutrophils. Herpes virus was verified via a positive polymerase chain reaction (PCR). Conjunctival scrapings for chlamydia immmunofluorescent antibody (IFA) and herpes IFA were negative. A mycoplasma was detected by a general mycoplasma PCR but the organism did not grow on the available mycoplasma media. The mass was excised and microscopic evaluation revealed a histiocytic mast cell tumor. The mast cell did not recur following local excision (at 1 year follow-up). The eosinophilic conjunctivitis was treated with both topical steroids and systemic megesterol acetate (Ovaban). When topical steroids were used, the herpes virus flared up and resulted in dendritic and geographic corneal ulceration. Therefore, the cat was treated with megesterol acetate and the eosinophilic conjunctivitis was well controlled. Treatment of eosinophilic conjunctivitis in the cat with megesterol acetate may be the treatement of choice due to the possibility of herpes virus.


Personal value, self-efficacy, and social acceptability of a social behavior as correlates of behavioral action in social anxiety.
Current therapies for social anxiety disorder emphasize taking behavioral action; active engagement of a behavior despite any present fear or anxiety that is associated with the behavior, through use of exposures. However, less is known about the mechanisms of behavioral action. The present study aimed to examine personal value, self-efficacy, and the perceived social acceptability of a social behavior as correlates of behavioral action in a high social anxiety sample. The present study utilized vignettes and self-report measures to examine self-efficacy, personal value, and the social acceptability of a social behavior as correlates of behavioral action in a high social anxiety sample (N = 92). The findings indicated that self-efficacy, but not personal value or social acceptability, was significantly associated with social anxiety. Additionally, with all variables included in the multiple regression model, social anxiety was significantly associated with behavioral action, while personal value and self-efficacy were associated with behavioral action over and above social anxiety. The results highlight the potential for self-efficacy and personal value as target mechanisms for increasing engagement with exposures and behavioral experiments in treatments for social anxiety.


IAC standardized reporting of breast fine-needle aspiration cytology, Yokohama 2016: A critical appraisal over a 2 year period.
Breast cytology is a significant component of the "Triple approach" for pre-operative diagnosis of breast lumps, the other two being clinical assessment and radiological imaging. The role of Fine needle aspiration cytology (FNAC) as a first line investigation in diagnosing breast lesions is well documented, however histopathology is the gold standard. Cyto-histopathological correlation is of great relevance and also increases precision.AIMS \& OBJECTIVES:The present study was conducted with the aim to categorize breast lesions according to the latest standardized reporting system proposed by International academy of cytologists (IAC) in 2016. Evaluation of diagnostic accuracy, sensitivity and specificity of FNAC in diagnosing breast lesions and cyto-histopathological correlation was planned. All FNAs of breast lesions over a period of 2 years were included in the study. The cases were grouped into five standardized categories proposed by the International academy of cytology: Category I (Insufficient material), Category II (Benign), Category III (Atypical, probably benign), Category IV (Suspicious, probably in situ or invasive) & Category V (Malignant) respectively. Specificity, sensitivity, diagnostic accuracy, negative and positive predictive value of FNAC were calculated and cyto-histopathological correlation assessed wherever possible. Out of 468 breast lesions reported on FNAC, the category wise distribution was - Category I, II, III, IV & V accounting for 23(4.9%), 342(73.07%), 7(1.5%), 11(2.35%) and 85(18.16%) respectively. Histopathology was performed in 331/468 cases with cyto histological concordance of 98.4% and a type agreement rate of 90.9%. The sensitivity, specificity, positive and negative predictive value and diagnostic accuracy was 98.90%, 99.16%, 97.82%, 99.58% and 99.09% respectively. FNAC is a simple, reliable, cost effective, first line diagnostic procedure for all breast lumps. In collaboration with physical examination and imaging studies (triple approach), FNAC is a highly sensitive diagnostic tool. Adopting a universally acceptable standardized reporting system for breast cytology can enhance the diagnostic accuracy of FNAC.


Management of idiopathic thrombocytopenic purpura in children: a single institution experience.
Idiopathic thrombocytopenic purpura (ITP) is a relatively common hematologic disease in childhood. ITP is often self-limiting and is characterized by a good clinical outcome. About 10-20% of cases can have a chronic course. In our retrospective analysis we have evaluated 45 patients affected by ITP from January '92 to December '97. Thirty-seven patients (82%) met the criteria of acute ITP and 8 (18%) had chronic ITP. Patients were stratified into 3 categories based up on the type of treatment received: no treatment, steroids, steroids and IVIG. In our series children treated with oral prednisone showed a slightly faster recovery in the first days from treatment. We suggest the use of steroids in children with low platelet count and signs and symptoms of bleeding.


Murine hypersensitivity pneumonitis: evidences for the role of eicosanoids and platelet activating factor.
Eicosanoids and platelet activating factor (PAF) are involved in numerous lung diseases. However, few studies have looked for their role in hypersensitivity pneumonitis (HP). HP was induced in mice by repeated instillations of Saccharapolyspora rectivirgula (Micropolyspora faeni) during 3 weeks. Bronchoalveolar lavages (BAL) were performed each week. BAL macrophage, lymphocyte and neutrophil counts increased at week 1, for a maximal increase after 3 weeks. Production of LTB4, LTC4, PGE2 and TXB2 by alveolar macrophages stimulated in vitro with calcium ionophore was maximal after 3 weeks, the appearance of PGE2 and TXB2 preceding that of LTB4 and LTC4. Eicosanoid production by AM correlated with BAL cell counts. To look for the importance of PAF in the development of experimental HP, mice were treated with BN52021 and BN50730, two PAF antagonists, and BAL were performed after 3 weeks of treatment. The compounds BN52021 and BN50730 reduced total BAL cell counts (x 10(5) cells/ml) in animals treated with S. rectivirgula from 8.4 +/- 0.8 to 4.4 +/- 1.1 and 3.7 +/- 0.2 respectively. BAL cell numbers in control animals were 0.4 +/- 0.1. In conclusion, eicosanoids are increased in experimental HP, and, as PAF, could play a role in the accumulation of alveolar cells.


In vivo He-3 MR images of guinea pig lungs.
The authors imaged the lungs of live guinea pigs with hyperpolarized (HP) helium-3 as a magnetic resonance (MR) signal source. HP He-3 gas produced through spin exchange with rubidium metal vapor was delivered through an MR-compatible, small-animal ventilator. Two- and three-dimensional lung images acquired with ventilation-gated, radial k-space sampling showed complete ventilation of both lungs. All images were of high quality, demonstrating that HP He-3 allows high-signal-intensity MR imaging in living systems.


The fluidity of blood in African elephants (Loxodonta africana).
The large cellular volume of erythrocytes and the increased plasma concentration of proteins in elephants are factors which potentially affect blood rheology adversely. To verify blood rheology, routine hemorheologic variables were analyzed in four African elephants (Loxodonta africana), housed in the zoo of Vienna. Whole blood viscosity at three different shear rates (WBV at low shear rate: WBV 0.7 s(-1) and WBV 2.4 s(-1); WBV at high shear rate: WBV 94 s(-1) done by LS30, Contraves) and erythrocyte aggregation (aggregation indices AI by LS30; aggregation indices M0, M1 by Myrenne aggregometer) were high (WBV 94 s(-1): 5.368 (5.246/5.648); WBV 2.4 s(-1): 16.291 (15.605/17.629); WBV 0.7 s(-1): 28.28 (25.537/32.173) mPa s; AI 2.4 s(-1): 0.25 (0.23/0.30); AI 0.7 s(-1): 0.24 (0.23/0.28); M0: 7.8 (6.4/8.4); M1: 30.2 (25/31)). Plasma viscosity (PV) was increased as well (1.865 (1.857/1.912) mPa s) compared to other mammalian species. These parameters would indicate a decrease in blood fluidity in elephants. However, erythrocyte rigidity (LORCA, Mechatronics) was decreased, which in contrast, has a promotive effect on peripheral perfusion. Blood rheology of the elephants was determined by a high whole blood and plasma viscosity as the result of pronounced erythrocyte aggregation and high plasma protein concentration. Thus, in the terminal vessels the resistance to flow will be increased. The large erythrocytes, which might impede blood flow further due to geometrical reasons, however, had a pronounced flexibility. We conclude that the effect of the increased inner resistance to peripheral blood flow was counteracted by the decreased rigidity of the erythrocytes to enable an adequate blood flow in African elephants.


Pressure ulcers at the end of life.
Skin compromise at the end of life (SCALE) is not a new concept. The development of SCALE at the end of life is often deemed unavoidable and a result of multiorgan failure resulting in tissue hypoperfusion, which leads to depletion of oxygen and nutrients for the skin. Pressure ulcers, formed due to pressure, shearing or continuous friction, are also common at the end of life. The goal of care for patients with pressure ulcers at the end of life is usually wound management and good quality of life, rather than wound healing. Nurses must assess all pressure ulcers or SCALE at the end of life holistically and consider treatment and management based on the patient's condition.


Improving intersubject image registration using tissue-class information benefits robustness and accuracy of multi-atlas based anatomical segmentation.
Automatic anatomical segmentation of magnetic resonance human brain images has been shown to be accurate and robust when based on multiple atlases that encompass the anatomical variability of the cohort of subjects. We observed that the method tends to fail when the segmentation target shows ventricular enlargement that is not captured by the atlas database. By incorporating tissue classification information into the image registration process, we aimed to increase the robustness of the method. For testing, subjects who participated in the Oxford Project to Investigate Memory and Aging (OPTIMA) and the Alzheimer's Disease Neuroimaging Initiative (ADNI) were selected for ventriculomegaly. Segmentation quality was substantially improved in the ventricles and surrounding structures (9/9 successes on visual rating versus 4/9 successes using the baseline method). In addition, the modification resulted in a significant increase of segmentation accuracy in healthy subjects' brain images. Hippocampal segmentation results in a group of patients with temporal lobe epilepsy were near identical with both approaches. The modified approach (MAPER, multi-atlas propagation with enhanced registration) extends the applicability of multi-atlas based automatic whole-brain segmentation to subjects with ventriculomegaly, as seen in normal aging as well as in numerous neurodegenerative diseases.


Dental needs, demands and patterns of service utilization in a selected Malaysian urban population.
The dental needs, demands and patterns of service utilization were assessed in a randomly selected sample of 750 subjects attending the Dental Faculty, University of Malaya, Kuala Lumpur. Toothache accounted for the most frequent overall dental complaint. However, the most common motives for seeking dental care varied among children (2-12 yr), adolescents (13-18 yr) and adults (19 + yr). The attendance behavior of women is more preventively orientated and more inclined towards rehabilitation compared to that of men. The proportion of normative needs of the patients varies from 7.5% for dentures to 66% for dental caries. About 50% of service utilization for the first visit consisted primarily of extractions in the oral surgery department.


[Prague's study of illegitimate children, part 2. Changes in mothers' family status].
The authors examine changes in the status of 327 single mothers in Czechoslovakia as part of a long-term study on the development of children born to unmarried parents. "There prevails the tendency to conclude marriage with [the] father or at least to live in a permanent union with another man. The number of single [mothers] remains rather low and the tendency towards creating matrimonial families thus predominates." (SUMMARY IN ENG AND RUS)


Sally Lucas Jean, R.N. (1878-1971): Her historical legacy and lessons for contemporary public health nursing education.
Sally Lucas Jean, RN (1878-1971) pioneered health education in the United States and globally. At the time of her death in 1971, aged 93, her legacy included serving on boards of leading American health associations, spearheading public health projects worldwide and transforming thinking on contemporary public health education. Sally Lucas Jean's influence continues today, from her input on educational children's television programs, policies on child health and her involvement in developing the early foundations of health communication. In this historical reflection, we examine her role in defining health education and communication, alongside influencing and applying strategies to improve public health nursing.


Using Population Health Measures to Evaluate the Environmental Burden of Cancer at the County Level.
Burden of disease is often defined by using epidemiologic measures. However, there may be latent aspects of disease burden that are not factored into these types of estimates. This study quantified environmental burden of disease by using population health indicators and exploratory factor analysis at the county level across the United States. Ninety-nine variables drawn from public use data sets from 2010 to 2016 were used to create a multifactor index - the burden index. We applied principal components analysis with promax rotation to allow the factors to correlate. Correlation coefficients for each factor and the outcome of interest, age-adjusted cancer death rate, were calculated. We used both unadjusted and adjusted linear regression techniques. The final additive county-level index included 9 factors that explained 68.3% of the variance in the counties and county equivalents. The burden index had a moderate association with the age-adjusted cancer death rates (r =.48, P <.001), and adjusted linear regression with all 9 factors explained 34% of the variance in the age-adjusted cancer death rate. Results were mapped, and the geographic distribution of both the burden index and age-adjusted cancer mortality were assessed. There are distinct geospatial patterns for both. Results from this study show potential areas of need, as well as the importance of including environmental variables in the study of cancer etiology. Future studies can aim to validate these findings by quantifying burden as it relates to overall cancer mortality by using epidemiologic measures, along with other confirmatory statistical methods.


Occurrence, Distribution, and Genetic Diversity of Alfalfa (Medicago sativa L.) Viruses in Four Major Alfalfa-Producing Provinces of China.
Alfalfa (Medicago sativa L.) is one of the most widely cultivated forage crops in the world. China is the second largest producer of alfalfa in terms of the planting area worldwide, with Gansu, Henan, Inner Mongolia, and Shaanxi provinces being the production hubs. Alfalfa viruses have been reported on a small-scale survey in some of these areas, but they have not been well characterized. In the present study, seven viruses were detected in 12 fields of 10 cities/counties of the four abovementioned provinces by high-throughput sequencing and assembly of small RNA. Their incidence, distribution, and genetic diversity were analyzed by enzyme-linked immunosorbent assay, polymerase chain reaction (PCR)/reverse transcription-PCR and clone sequencing. The results showed that alfalfa mosaic virus (AMV), pea streak virus (PeSV), lucerne transient streak virus (LTSV), alfalfa dwarf virus (ADV), Medicago sativa alphapartitivirus 1 (MsAPV1), MsAPV2, and alfalfa leaf curl virus (ALCV) were the main viruses infecting alfalfa in four examined provinces. AMV and MsAPV1 had the highest incidences in all 4 provinces. SDT analysis of the 7 viruses isolated in China revealed a highly conserved among AMV, LTSV, ADV, MsAPV1, MsAPV2, and ALCV, but the sequence was a high variation between China isolates to abroad isolates in PeSV, ADV, and ALCV. To our knowledge, this is the first report of ADV in Inner Mongolia and Gansu, ALCV in Inner Mongolia, MsAPV1 and MsAPV2 in all 4 provinces, and PeSV and LTSV in China. These findings provide a basis for future research on the genetic evolution of alfalfa viruses in China and on strategies to prevent diseases in alfalfa caused by these viruses.


Regulatory Mechanisms of Vitellogenesis in Insects.
Vitellogenesis is pre-requisite to insect egg production and embryonic development after oviposition. During insect vitellogenesis, the yolk protein precursor vitellogenin (Vg) is mainly synthesized in the fat body, transported by the hemolymph through the intercellular spaces (known as patency) in the follicular epithelium to reach the membrane of maturing oocytes, and sequestered into the maturing oocytes via receptor-mediated endocytosis. Insect vitellogenesis is governed by two critical hormones, the sesquiterpenoid juvenile hormone (JH) and the ecdysteriod 20-hydroxyecdysone (20E). JH acts as the principal gonadotropic hormone to stimulate vitellogenesis in basal hemimetabolous and most holometabolous insects. 20E is critical for vitellogenesis in some hymenopterans, lepidopterans and dipterans. Furthermore, microRNA (miRNA) and nutritional (amino acid/Target of Rapamycin and insulin) pathways interplay with JH and 20E signaling cascades to control insect vitellogenesis. Revealing the regulatory mechanisms underlying insect vitellogenesis is critical for understanding insect reproduction and helpful for developing new strategies of insect pest control. Here, we outline the recent research progress in the molecular action of gonadotropic JH and 20E along with the role of miRNA and nutritional sensor in regulating insect vitellogenesis. We highlight the advancements in the regulatory mechanisms of insect vitellogenesis by the coordination of hormone, miRNA and nutritional signaling pathways.


Neddylation blockade induces HIF-1α driven cancer cell migration via upregulation of ZEB1.
Neddylation is a process by which NEDD8 is covalently conjugated to target proteins by sequential enzymatic reaction. Its role in cancer cell migration has only been recently acknowledged. Previously in cancer cell migration, the epithelial to mesenchymal transition (EMT) process has been well-known to play an important role in both invasion and metastasis by promoting mesenchymal phenotype in epithelial cells. However, the role of neddylation in the EMT process and its mechanistic details are yet to be elucidated. We recently reported that neddylation plays a crucial role in cancer cell migration through the PI3K-Akt pathway. Here, we report that inhibiting neddylation activates the hypoxia-inducible factor 1α (HIF-1α) through the PI3K-Akt pathway, which eventually regulates the EMT-activator ZEB1 (zinc finger E-box binding homeobox 1) in various cancer cell lines. As induction of HIF-1α is known to deteriorate the state of cancer and EMT process is one of the hallmarks of metastasis in cancer, our findings uncover the role of neddylation between HIF-1α and ZEB1.


Zinc deficiency: a frequent and underestimated complication after bariatric surgery.
Although zinc deficiency is common after bariatric surgery, its incidence is underestimated. The objective was to monitor zinc and nutritional status before and 6, 12 and 24 months (M6, M12 and M24) after gastric bypass (Roux-en-Y gastric bypass), sleeve gastrectomy and biliopancreatic diversion with duodenal switch (DS) in patients receiving systematised nutritional care. Data for 324 morbidly obese patients (mean body mass index 46.2 ± 7.3 kg/m(2)) were reviewed retrospectively. The follow-up period was 6 months for 272 patients, 12 months for 175, and 24 months for 70. Anthropometric, dietary and serum albumin, prealbumin, zinc, iron and transferrin saturation measures were determined at each timepoint. Nine percent of patients had zinc deficiency pre-operatively. Zinc deficiency was present in 42.5% of the population at M12 and then remained stable. Zinc deficiency was significantly more frequent after DS, with a prevalence of 91.7% at M12. Between M0 and M6, variation in plasma prealbumin, surgery type and zinc supplementation explained 27.2% of the variance in plasma zinc concentration. Surgery type explained 22.1% of this variance between M0 and M24. Mean supplemental zinc intake was low (22 mg/day). The percentage of patients taking zinc supplementation at M6, M12 and M24 was 8.9%, 20.6% and 29%, respectively. Reduced protein intake, impaired zinc absorption and worsening compensatory mechanisms contribute to zinc deficiency. The mechanisms involved differ according to the type of surgery and time since surgery. Zinc supplementation is necessary early after bariatric surgery, but this requirement is often underestimated or is inadequate.


Tumor necrosis factor-alpha inhibits in vivo collagen synthesis.
In this study we sought to determine the in vivo role of tumor necrosis factor-alpha (TNF-alpha) at the wound-healing site. In vivo abrogation of endogenous TNF-alpha activity in experimental wounds by administration of anti-murine TNF-alpha rabbit serum resulted in a significant 77.5% increase in wound collagen deposition, as assessed by wound sponge granuloma hydroxyproline content. Administration of pharmacologic doses of recombinant murine TNF-alpha into subcutaneously inserted polyvinyl alcohol sponges resulted in an increase in collagen deposition (1594 +/- 117 vs 1014 +/- 49 and 1588 +/- 135 vs 1014 +/- 49 micrograms/100 mg sponge, for TNF-alpha in situ administration at a dose of 0.05 and 0.5 micrograms, respectively). This effect could be abolished by the simultaneous systemic treatment of the animals with the antiinflammatory drug indomethacin. The data suggest that the enhanced collagen deposition after TNF-alpha administration is a consequence of a nonspecific inflammatory activity that indirectly promotes collagen synthesis. The data also support the hypothesis that endogenous wound TNF-alpha down-regulates collagen synthesis during normal wound healing.


[Thrombopenia induced by heparin].
The authors report three cases of heparin-induced thrombocytopenia. Two cases were associated with deep venous thrombosis and pulmonary embolism and the other case was associated with arterial embolism. The clinical course was serious, with one death and one amputation of a limb. The thrombocytopenia developed suddenly, 10 to 15 days after the start of treatment; the platelet count was always below 100 000/mm3. The platelet aggregation test is an important diagnostic element, together with the rapid return to normal of the platelet count once the heparin is stopped. An anti-platelet antibody was detected in two patients, suggesting an immuno-allergic mechanism for this new complication of heparin treatment. The treatment consist of immediately stopping the heparin and replacing it with an anti-vitamin K drug or low-molecular weight heparin. The platelet count should be monitored systematically in all patients receiving heparin treatment for more than 8 days.


Calcified peritoneal metastasis identified on 18F-fluoride positron emission tomography/computed tomography: Importance of extraosseous uptake of F-18 fluoride.
F-18 NaF positron emission tomography/computed tomography (PET/CT) is used for the evaluation of malignant and nonmalignant osseous disease. Extraosseous uptake of 18 fluoride-NaF has been observed in the arterial vasculature, gastrointestinal tract, and genitourinary tract. We describe a case of a woman with carcinoma of unknown primary in whom F-18 NaF PET/CT showed tracer uptake in the calcified peritoneal metastasis. Extraosseous findings on F-18 NaF PET/CT, though rare, may be visualized and may result in important management changes.


Adenomatous Polyposis Coli as a Scaffold for Microtubule End-Binding Proteins.
End-binding proteins (EBs), referred to as the core components of the microtubule plus-end tracking protein network, interact with the C-terminus of the adenomatous polyposis coli (APC) tumor suppressor. This interaction is disrupted in colon cancers expressing truncated APC. APC and EBs act in synergy to regulate microtubule dynamics during spindle formation, chromosome segregation and cell migration. Since EBs autonomously end-track microtubules and partially co-localize with APC at microtubule tips in cells, EBs have been proposed to direct APC to microtubule ends. However, the interdependency of EB and APC localization on microtubules remains elusive. Here, using in vitro reconstitution and single-molecule imaging, we have investigated the interplay between EBs and the C-terminal domain of APC (APC-C) on dynamic microtubules. Our results show that APC-C binds along the microtubule wall but does not accumulate at microtubule tips, even when EB proteins are present. APC-C was also found to enhance EB binding at the extremity of growing microtubules and on the microtubule lattice: APC-C promotes EB end-tracking properties by increasing the time EBs spend at microtubule growing ends, whereas a pool of EBs with a fast turnover accumulates along the microtubule surface. Overall, our results suggest that APC is a promoter of EB interaction with microtubules, providing molecular determinants to reassess the relationship between APC and EBs.


Voltage gated calcium channels negatively regulate protective immunity to Mycobacterium tuberculosis.
Mycobacterium tuberculosis modulates levels and activity of key intracellular second messengers to evade protective immune responses. Calcium release from voltage gated calcium channels (VGCC) regulates immune responses to pathogens. In this study, we investigated the roles of VGCC in regulating protective immunity to mycobacteria in vitro and in vivo. Inhibiting L-type or R-type VGCC in dendritic cells (DCs) either using antibodies or by siRNA increased calcium influx in an inositol 1,4,5-phosphate and calcium release calcium activated channel dependent mechanism that resulted in increased expression of genes favoring pro-inflammatory responses. Further, VGCC-blocked DCs activated T cells that in turn mediated killing of M. tuberculosis inside macrophages. Likewise, inhibiting VGCC in infected macrophages and PBMCs induced calcium influx, upregulated the expression of pro-inflammatory genes and resulted in enhanced killing of intracellular M. tuberculosis. Importantly, compared to healthy controls, PBMCs of tuberculosis patients expressed higher levels of both VGCC, which were significantly reduced following chemotherapy. Finally, blocking VGCC in vivo in M. tuberculosis infected mice using specific antibodies increased intracellular calcium and significantly reduced bacterial loads. These results indicate that L-type and R-type VGCC play a negative role in M. tuberculosis infection by regulating calcium mobilization in cells that determine protective immunity.


Clinical aspects of oral implantology.
During the past few decades the use of implants in dentistry has increased markedly. Endosteal titanium implants are now most commonly used for replacement of single teeth and partial and full dentition. The success rates reported for osseointegrated implants depend on the type of implant and the criteria of success. Results are better for the mandible than the maxilla. Patient selection, careful planning of surgical and prosthetic treatment, and atraumatic, aseptic surgical procedures are essential for successful results. This article reviews various implant methods used in our Department and gives examples of treatment in particular clinical situations.


Deletion of the oxygen-dependent degradation domain results in impaired transcriptional activity of hypoxia-inducible factors.
Hypoxia-inducible factors (HIF1α/HIF2α) are key transcription factors that promote angiogenesis. The overexpression of degradation-resistant HIF mutants is considered a promising pro-angiogenic therapeutic tool. We compared the transcriptional activity of HIF1α/HIF2α mutants that obtained their resistance to oxygen-dependent degradation either by deletion of their entire oxygen-dependent degradation (ODD) domain or by replacement of prolyl residues that are crucial for oxygen-dependent degradation. Although all HIF mutants translocated into the nucleus, HIF1α and HIF2α mutants inclosing the point mutations were significantly more effective in trans-activating the target gene VEGF and in inducing tube formation of endothelial cells than mutants lacking the complete ODD domain.


Exercise Interventions to Reduce Cancer-Related Fatigue and Improve Health-Related Quality of Life in Cancer Patients.
Cancer-related fatigue (CRF) is the most common and debilitating side effect of patients receiving treatment of cancer. It is reported that 60% to 100% of patients will develop CRF as a result of the treatment or the cancer itself. The effects last for years posttreatment and lower overall quality of life. The purpose of this integrative review was to determine whether exercise interventions could reduce CRF and improve overall health-related quality of life (HRQOL) among selected cancer patients. Clinical Key, ProQuest Nursing and Allied Health Source, Cochrane Library, Mosby's Nursing Consult, and MEDLINE (Ovid) were the databases searched. Key terms searched were fatigue, exercise, cancer fatigue, holistic, spiritual, quality of life, and prevention. Findings from most studies suggest that exercise can decrease the effects of CRF among cancer patients, leading to an overall improved HRQOL. No negative results on the effects of exercise on CRF were reported. Nurses can be instrumental in developing holistic multidisciplinary exercise programs to assist in the management of CRF and improve HRQOL among cancer patients during and after cancer treatment. Recommendations for future research include the need for larger study sample sizes, a universal definition of fatigue, determination of the best exercise regimens, more consistent fatigue measures to facilitate better comparison across studies, and specifically assess patient improvements in overall mental and spiritual well-being within a holistic framework.


Can a community-based multidisciplinary intervention effectively restore renal function? A non-randomized clinical trial.
There is insufficient evidence in the literature to indicate whether the promotion of lifestyle changes to prevent renal dysfunction and activate regeneration is effective. We examined the effectiveness of a community-based intervention program on renal restoration using a non-randomized clinical trial design with a follow-up period of six months. The training focused on lifestyle changes, including health education and personal consultation with a multidisciplinary health team. Our study included 120 patients with fractional excretion of magnesium levels of > 2%, who were assigned to experimental or control groups. Fractional excretion of magnesium levels were significantly decreased within six months in the experimental group; however, changes in the estimated glomerular filtration rate were not identified in either of the groups. These results suggest that screening of the fractional excretion of magnesium level and the "Healthy Kidney Program" had an effect in preventing chronic kidney disease or restoring kidney function.


Evaluation of sulfuric acid-pretreated biomass-derived biochar characteristics and its diazinon adsorption mechanism.
In this study, hemicellulose was mostly removed from biomass (larch and oak) using a sulfuric acid pretreatment. Biochar was then prepared from raw and pretreated biomass using a carbonization process. Biochar derived from pretreated biomass had an aromatic and graphitized structure, and functional groups were observed on the surface. The specific surface area was higher for biochar obtained from pretreated biomass than biochar derived from raw biomass. The biochar obtained from pretreated biomass contained a greater number of micropores than biochar derived from raw biomass. The diazinon removal rate was the highest for biochar that was obtained from pretreated biomass when 10% of the biochar was added to the soil. As a result of the adsorption of diazinon onto the biochar obtained from pretreated biomass, the R2 value of the Langmuir isotherm was higher than that of the Freundlich's R2.


Associations Between Defence-Style, Eating Disorder Symptoms, and Quality of Life in Community Sample of Women: A Longitudinal Exploratory Study.
Background and Aim: Eating Disorders (EDs) impact an estimated 15% of the global population and are linked to maladaptive defence-styles (coping strategies) and poorer mental health outcomes. Defence-styles have been grouped into immature, neurotic, and mature behaviours. Studies have yet to examine all three defence-styles in ED symptomatic individuals over an extended period of time. The current study aimed to investigate using converse analysis the relationships between defence-style and ED outcomes over a 5-years period. Methods: Participants (n = 216, mean age 33 years) were recruited through the Women's Eating and Health Literacy study, with the current study examining a 5-years period of two waves (year-4 and year-9). The current study tested associations over time between eating pathology (EDE-Q), psychological distress (K10), mental and physical health related quality of life (M/PHRQoL, SF-12), and defence-style (DSQ-40). Results: Mature, immature and neurotic defence-styles did not significantly change over 5 years. Over the same period, only PHRQoL significantly predicted mature defence-styles having positive effect. Both MHRQoL and PHRQoL significantly predicted immature defence-styles having positive and negative effects, respectively. Psychological distress, PHRQoL and weight concern significantly predicted neurotic defence-styles having positive effects except for psychological distress. PHRQoL, MHRQoL, restraint and eating concern significantly predicted overall eating pathology having positive effects except for PHRQoL and MHRQoL. Conversely, among the defence-style variables, over 5 years, both immature and neurotic defence-styles significantly predicted psychological distress having positive effects, immature and mature defence-styles significantly predicted MHRQoL having negative and positive effects, respectively, while only immature defence-styles significantly predicted overall eating pathology having positive effect. Conclusions: The results of the current study suggest that immaturity and neuroticism but not maturity were the defence-style variables predicting psychological distress over a 5-years period while conversely psychological distress predicted only neurotic defence styles. The findings of the current study may suggest that without intervention, mature, immature and neurotic defence-styles may largely remain immutable to significant shifts over time. Limitations in the current study included limited demographic representation. The current study is anticipated to generate considerations into treatments that could strengthen defence-styles in individuals with increased eating pathology.


The association between blood concentration of 25- hydroxyvitamin D and sarcopenia: a meta-analysis.
Associations between blood 25-hydroxyvitamin D (25(OH)D) concentration and sarcopenia remain controversial; thus, this meta-analysis was conducted to explore the relationship between blood 25(OH)D concentration and sarcopenia. We searched the PubMed and EMBASE databases for relevant published observational studies that investigated blood 25(OH)D concentration and sarcopenia up to June 2017.We then investigated data from these studies that compared blood 25(OH)D concentrations between the sarcopenia and healthy control groups. A random-effect model was used to calculate the pooled weighted mean difference (WMD) of blood 25(OH)D concentration with a 95% confidence interval (95% CI). Twelve studies (eight cross-sectional, two matched case-control, and two prospective cohort studies) with a total of 22,590 individuals were included. Sarcopenic individuals had lower blood 25(OH)D concentrations than healthy controls (WMD=-2.14, 95% CI: -2.81--1.48; I2=74.6%). Subgroup analysis showed that the methods of assessing both blood 25(OH)D concentrations and sarcopenia might be sources of heterogeneity, and further showed that studies excluding obese individuals and different sarcopenia assessment criteria enhanced the relationship. Sensitivity analysis by one-study-removed confirmed the robustness of these results. Our study shows that sarcopenic adults have lower blood 25(OH)D concentrations. Further high-quality large-scale prospective cohort studies are needed to confirm these findings.


Sound propagation in a turbulent atmosphere near the ground: a parabolic equation approach.
The interference of the direct wave from the point source to the receiver and the wave reflected from the impedance ground in a turbulent atmosphere is studied. A parabolic equation approach for calculating the sound pressure p at the receiver is formulated. Then, the parabolic equation is solved by the Rytov method yielding expressions for the complex phases of direct and ground-reflected waves. Using these expressions, a formula for the mean squared sound pressure [absolute value(p)2] is derived for the case of anisotropic spectra of temperature and wind velocity fluctuations. This formula contains the "coherence factor," which characterizes the coherence between direct and ground-reflected waves. It is shown that the coherence factor is equal to the normalized coherence function of a spherical sound wave for line-of-sight propagation. For the case of isotropic turbulence, this result allows one to obtain analytical formulas for [absolute value(p)2] for the Kolmogorov, Gaussian, and von Karman spectra of temperature and wind velocity fluctuations. Using these formulas, the effects of temperature and wind velocity fluctuations, and the effects of different spectra of these fluctuations on the mean squared sound pressure, are numerically studied. Also the effect of turbulent anisotropy on the interference of direct and ground reflected waves is numerically studied. Finally, it is shown that the mean squared sound pressure [absolute value(p)2] calculated for the von Karman spectrum of temperature fluctuations agrees well with experimental data obtained in a laboratory experiment.


Accuracy of real-time ultrasound elastography in the differential diagnosis of lymph nodes in cutaneous malignant melanoma (CMM): a pilot study.
We investigated the diagnostic ability of real-time elastography to differentiate between reactive and metastatic lymph nodes in cutaneous malignant melanoma (CMM) patients and to determine the optimum cutoff value for elastography scores for diagnosis CMM. Twenty lymph nodes (metastatic, n = 13; reactive, n = 7) from 12 patients with CMM were examined by both elastography and B-mode ultrasound in this prospective study. Elastographic patterns were given scores of 1-5 according to the percentage of high elasticity (hard) areas in the lymph node. Elastographic patterns 1, 2, 3, 4, and 5 were assigned elastography scores (ES) of 1, 2, 3, 4, and 5, respectively. B-mode ultrasound diagnosis was performed on the basis of the morphological patterns (balloon-shaped lymph node and loss of central echoes). The sensitivity, specificity, and accuracy were calculated, and receiver operating characteristic analysis was performed, comparing with elastograms and B-mode images, with histological findings as the reference standard. Sensitivity, specificity, and accuracy of elastography were 100, 71, and 90 %, respectively, with an ES cutoff value of 3; 92, 100, and 95 % for elastography with an ES cutoff value of 4; and 77, 57, and 70 % for B-mode ultrasound. Elastography can enhance the diagnostic accuracy of ultrasound for differentiating between reactive and malignant lymph nodes in CMM and might eliminate the need for sentinel lymph node biopsy. The optimum ES cutoff value for reactive versus metastatic lymph nodes is 4.


FoxO proteins in the nervous system.
Acute as well as chronic disorders of the nervous system lead to significant morbidity and mortality for millions of individuals globally. Given the ability to govern stem cell proliferation and differentiated cell survival, mammalian forkhead transcription factors of the forkhead box class O (FoxO) are increasingly being identified as potential targets for disorders of the nervous system, such as Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, and auditory neuronal disease. FoxO proteins are present throughout the body, but they are selectively expressed in the nervous system and have diverse biological functions. The forkhead O class transcription factors interface with an array of signal transduction pathways that include protein kinase B (Akt), serum- and glucocorticoid-inducible protein kinase (SgK), IκB kinase (IKK), silent mating type information regulation 2 homolog 1 (S. cerevisiae) (SIRT1), growth factors, and Wnt signaling that can determine the activity and integrity of FoxO proteins. Ultimately, there exists a complex interplay between FoxO proteins and their signal transduction pathways that can significantly impact programmed cell death pathways of apoptosis and autophagy as well as the development of clinical strategies for the treatment of neurodegenerative disorders.


Sexual Orientation, Controversy, and Science.
SummaryOngoing political controversies around the world exemplify a long-standing and widespread preoccupation with the acceptability of homosexuality. Nonheterosexual people have seen dramatic surges both in their rights and in positive public opinion in many Western countries. In contrast, in much of Africa, the Middle East, the Caribbean, Oceania, and parts of Asia, homosexual behavior remains illegal and severely punishable, with some countries retaining the death penalty for it. Political controversies about sexual orientation have often overlapped with scientific controversies. That is, participants on both sides of the sociopolitical debates have tended to believe that scientific findings-and scientific truths-about sexual orientation matter a great deal in making political decisions. The most contentious scientific issues have concerned the causes of sexual orientation-that is, why are some people heterosexual, others bisexual, and others homosexual? The actual relevance of these issues to social, political, and ethical decisions is often poorly justified, however.


Immunodetection of squamous cell carcinoma-associated variant of nuclear protein.
A new monoclonal antibody, MAb C63.3, was developed by immunizing mice with the high molecular weight fraction of the cytoplasmic proteins from the cervical squamous cell carcinoma. In Western blotting, MAb C63.3 reacted with cytoplasmic and chromatin antigens expressed by cervical and vulvar squamous cell carcinomas and much weaker with normal cervical tissue and skin cells. Different molecular variants of C63.3 chromatin antigens were found in normal tissues (heavy variants, M(r) 65,000 and 59,000) compared to squamous cell carcinomas (light variant, M(r) 48,000). Diagnostic value of the cancer-associated M(r) 48,000 antigen is discussed. MAb C63.3 was internalized by cells and bound to the chromatin which suggests that antigen(s) C63.3 might represent a receptor for a yet unknown ligand (growth factor). It is suggested that the high molecular weight C63.3 antigens play a role in maintaining the nonmalignant phenotype.


Serum and coproantibody responses to rotavirus infection in children during the first two years of life.
The serum and coproantibody response (IgG and IgA) to naturally acquired rotavirus infections and reinfections in the first two years of life were studied in 13 cases and 12 control children using enzyme-immunoassay. A 100% IgG seroconversion and coproconversion occurred after tertiary and quaternary infections respectively. Unlike the IgA coproantibody response, serum IgG was detected more frequently after symptomatic (89%) than asymptomatic (50%) infections, and its duration and titre were boosted by reinfections. The durations of both responses was prolonged when reinfection occurred at 15 months versus 8 months. Both responses were observed after primary infection in the first two months of life. Higher instances of virus reinfections were detected serologically (72.5%) than virologically (27%). The results suggest that at least 3 doses of a rotavirus vaccine will be required before 4 months plus boosters around the 10th and 15th months. Further, during vaccine trials, virus infections should be monitored virologically and serologically.


Comments on Depreitere et al. Lateral head impacts and protection of the temporal area by bicycle safety helmets. J. Trauma. 2007;62:1440.
The side of the head is vulnerable to trauma in bicycle injuries. Depreitere et al., demonstrated contact between a flat-faced pendulum, and the side of cadaver heads, when bicycle helmets was worn. Computer design methods were used to interpret these experiments, showing that typical helmets safely absorbed 75% of the impact kinetic energy before pendulum-to-head contact occurred. Furthermore, in typical oblique impacts with the road, two factors improve the head protection. The tangential velocity component slightly improves the helmet performance, whereas prior shoulder impact on the road decreases the head impact velocity. It is concluded that current helmets provide adequate protection for typical lateral head impacts.


[Preliminary study of proteins related to blast crisis in chronic myeloid leukemia].
To identify and compare the expression profiles of differential proteins between chronic phase and blast crisis in chronic myeloid leukemia (CML) by proteomic analysis, and screen the proteins related to blast crisis. The total cellular proteins from the bone marrow cells at chronic phase (CP) and blast crisis (BC) in CML were separated by two-dimensional polyacrylamide gel electrophoresis (2-DE) and analyzed with ImageMaster 5.0 software to screen the differential protein spots. Differential protein spots were identified by mass spectrometry for peptide mass fingerprint in combination with database searching from SWISS-PROT. Then 3 protein spots were selected to verify at protein and mRNA levels by Western blot and semi-quantitative RT-PCR, separately. Comparing gel pages from CML-CP and CML-BC, the expression of 13 protein spots decreased and 25 protein spots increased significantly in CML-BC. Twenty differential protein spots were identified by mass spectrometry and 15 were successfully determined. The results of Western blotting were similar to those of 2-DE and showed a high expression of hnRNPK, annexin A1 and RhoA. Semi-quantitative RT-PCR analysis showed that there was no correlation between the protein expression changes and mRNA levels of hnRNPK, annexin A1 and RhoA. A group of proteins associated with blast crisis are obtained and the results may provide clues for further research to elucidate the role of these proteins in CML-BC carcinogenesis and to develop potential associated biomarkers.


[Effectiveness of a home hospitalization program for patients with urinary tract infection after discharge from an emergency department].
To compare outcomes of urinary tract infections (UTIs) in patients referred to a home hospitalization program or admitted to a conventional ward after initial management in the emergency department. Prospective, quasi-experimental study of patients with UTIs attended in 3 hospital emergency departments in the public health system of the Basque Country, Spain, between January 2012 and June 2013. Patients were assigned to 2 groups according to site of treatment (home or hospital ward) after discharge from the emergency department. We collected sociodemographic data, history of kidney or urologic symptoms, concomitant diseases, risk for complicated UTI, presentation on admission to the emergency department, diagnostic findings, and prescribed treatments. The main outcome was poor clinical course (local complications during hospital or home care, recurrence, or readmission related to UTI. Multivariate logistic modeling was used to analyze factors related to poor clinical course. Home hospitalization was the main independent variable of interest. Patients referred to home hospitalization were more often women (70.6% vs 57.1% men, P=.04). Fewer cases of prior admission were recorded in the group treated at home (2.4% vs 9.5% of hospitalized patients, P=.03). Likewise, fewer home-hospitalization patients had risk factors for complicated UTI (58.7% vs 83.3% in the hospitalized group, P<.001). The only significant difference in complications between the 2 groups was a lower rate of acute confusional state in patients assigned to home hospitalization (0.8% vs 8.3% in hospitalized patients, P=.007). The frequency of poor clinical course was similar in home-hospitalized and ward-admitted patients. The clinical course of UTI is similar whether patients are hospitalized after emergency department management or discharged to a home hospitalization program.


The risk of tendon xanthomas in familial hypercholesterolaemia is influenced by variation in genes of the reverse cholesterol transport pathway and the low-density lipoprotein oxidation pathway.
The presence of tendon xanthomas is a marker of high risk of cardiovascular disease (CVD) among patients with familial hypercholesterolaemia (FH). Therefore, xanthomas and atherosclerosis may result from the same pathophysiological mechanisms. Reverse cholesterol transport (RCT) and low-density lipoprotein (LDL) oxidation are pathophysiological pathways of atherosclerosis, and it is well established that genetic variation in these pathways influences CVD risk. We therefore determined whether genetic variation in these pathways is also associated with the occurrence of tendon xanthomas in FH patients. Four genetic variants in each pathway were genotyped in 1208 FH patients. We constructed a gene-load score for both pathways. The odds of xanthomas increased with the number of the risk alleles in the RCT pathway (OR 1.21, 95% CI 1.08-1.36, P(trend) = 0.0014). Similarly, higher numbers of risk alleles in the LDL oxidation pathway were associated with the presence of xanthomas (OR 1.24, 95% CI 1.08-1.41, P(trend) = 0.0015). The presence of tendon xanthomas in FH patients is associated with genetic variation in the RCT and LDL oxidation pathways. These results support the hypothesis that xanthomas and atherosclerosis share pathophysiological mechanisms.


MicroRNA-9 regulates the development of knee osteoarthritis through the NF-kappaB1 pathway in chondrocytes.
It has been suggested that microRNA-9 (miR-9) is associated with the development of knee osteoarthritis (OA). This study was aimed to investigate the association between the mechanism of miR-9 targeting nuclear factor kappa-B1 (NF-κB1) and the proliferation and apoptosis of knee OA chondrocytes.Cartilage samples were collected from 25 patients with knee OA and 10 traumatic amputees, and another 15 OA rat models, together with 15 rats without knee OA lesions were also established. MiR-9 expressions in both knee OA cartilage and normal cartilage samples were detected using quantitative real-time PCR. The expressions of related genes (NF-κB1, IL-6, and MMP-13) in the two groups were also detected. Dual luciferase reporter gene assay was employed to examine the effect of miR-9 on the luciferase activity of NF-κB1 3'UTR. Knee OA chondrocytes were transfected with miR-9 mimics, miR-9 inhibitor, and NF-κB1 siRNA, respectively, and changes in cellular proliferation and apoptosis were detected via MTT assay and flow cytometric analysis, respectively. Western blotting assay was used to detect the expressions of NF-κB1, interleukin-6 (IL-6), and matrix metalloproteinase-13 (MMP-13).According to results from human OA samples and rat OA models, miR-9 was significantly downregulated in knee OA cartilage tissues compared with normal cartilage tissues (P < 0.01). The expressions of NF-κB1, IL-6, and MMP-13 in knee OA cartilage tissues were significantly higher than those in normal cartilage tissues (P < 0.01). Dual luciferase reporter gene assay showed that miR-9 could bind to the 3'UTR of NF-κB1 and significantly inhibit the luciferase activity by 37% (P < 0.01). Upregulation of miR-9 or downregulation of NF-κB1 could promote cell proliferation and suppress cell apoptosis.Conclusively, downregulated miR-9 can facilitate proliferation and antiapoptosis of knee OA chondrocytes by directly binding to NF-kB1, implying that stimulating miR-9 expressions might assist in treatment of knee OA.


Bradykinin-stimulated transient modulation of epidermal growth factor receptors in A-431 human epidermoid carcinoma cells.
Of nine biological factors (ATP, bradykinin, vasopressin, substance P, angiotensin II, norepinephrine, epinephrine, 12-tetradecanoylphorbol 13-acetate (TPA), and A23187 calcium ionophore) examined, bradykinin, as well as ATP, TPA, and A23187, significantly increased the phosphorylation of epidermal growth factor (EGF) receptors and reduced the binding of EGF to their high-affinity site. The reduction in EGF binding by bradykinin, ATP, and TPA was similarly reversed by concomitant incubation with staurosporine, a protein kinase C inhibitor, implying that the phosphorylation of EGF receptors was catalyzed probably by a protein kinase C of the same or similar type in each case. This possibility was confirmed by the fact that the major phosphorylation site of EGF receptors by the stimulation with either bradykinin, ATP, or TPA was the same (Thr-654). Different from the stimulations with ATP and TPA, the effect of bradykinin of decreasing the high-affinity EGF binding was transient (a minimum binding at 2.5 min); the reduced EGF binding was, however, sustained for up to 30 min in the presence of calyculin A, a phosphoprotein phosphatase inhibitor. Moreover, the homogenate prepared from bradykinin-stimulated A-431 cells had stronger dephosphorylation activity for phosphorylated EGF receptors than that from control cells. These results suggest that bradykinin stimulates both the protein kinase C system and a phosphoprotein phosphatase(s) activity in A-431 cells. Such biphasic effects of bradykinin to phosphorylate and dephosphorylate EGF receptors via protein kinase C and a phosphoprotein phosphatase, respectively, imply a homeostatic control of receptor function in regulating phosphorylation level by the same bioactive factor.


[Surgical management of vascular ring in 5 cases].
Five cases of vascular ring are presented. Three cases have double aortic arch and two cases have right aortic arch with aberrant left subclavian artery. Other congenital heart diseases are complicated in four cases. MRI was useful for the evaluation of tracheal and esophageal compression.


Reversal of pulmonary hypertension after diaphragm pacing in an adult patient with congenital central hypoventilation syndrome.
Patients with the congenital central hypoventilation syndrome (CCHS) suffer from life-threatening hypoventilation when asleep, making them dependent on mechanical ventilation (MV) at night or during naps. State-of-art respiratory management consists of intermittent positive-pressure ventilation via a tracheotomy or mask. In some patients hypoventilation is permanent, in which case ventilatory support must be extended to the waking hours. Diaphragm pacing can prove useful in such situations. This report describes the case of a 26-year-old woman with CCHS in whom failure to achieve adequate MV led to life-threatening pulmonary hypertension (PH), with a systolic pulmonary artery pressure (PAP) of 80 mmHg and right ventricular hypertrophy, despite optimization of all possible measures and despite extensive therapeutic education efforts. Diaphragm pacing using laparoscopically implanted intradiaphragmatic phrenic nerve stimulation electrodes corrected alveolar hypoventilation and lastingly reversed PH (systolic PAP below 40 mmHg after 2 months, sustained after 2 years). Diaphragm pacing induced shoulder pain, however, involving the chronic use of analgesics. The pacing had to be stopped for tolerance reasons after two years, leading to PH worsening and the need for diurnal MV. Diaphragm pacing appears likely effective to restore alveolar ventilation and reverse PH in adult CCHS patients.


Phasmarhabditis bonaquaense n. sp. (Nematoda: Rhabditidae), a new slug-parasitic nematode from the Czech Republic.
Phasmarhabditis bonaquaense n. sp. is described and illustrated from the body of Malacolimax tenellus, from the locality of České Švýcary near the village of Dobrá Voda, the Czech Republic. Females are characterized by a body length of 2349 (1878-2626) µm and a cupola shaped tail with a long hyaline hair-like tail tip. Extremely prominent papilla-like phasmids present. Males 1829 (1414-2121) µm long. Peloderan bursa with nine pairs of rays (papillae), 1/1/1/2/1/3. One non-paired apparent papilla-like structure located near the ventral appendage anterior to the cloaca. Prominent papilla-like phasmids located close to the tail tip. Small subunit (18S), ITS, and D2-D3 expansion segments of the large subunit of ribosomal DNA were used to analyze the phylogenetic relationships of sequenced species in the genus Phasmarhabditis and other closely related species. Phasmarhabditis bonaquaense n. sp. varied from other related nematodes both in morphological characterizations and phylogenetic analysis. The life cycle of the newly described species is not well known but it is probably a facultative, mollusc-parasitic nematode able to survive permanently in the saprobic phase on decaying organic matter.


Skeletal muscle fibre characteristics in young women.
Muscle samples were obtained by needle biopsy from the lateral vastus muscle of 54 healthy female subjects, 18 to 40 years of age. 25 subjects were classified as sedentary, 20 as active, and 9 as endurance trained. In 33 of the subjects, the deltoid muscle was biopsied as well. The lateral vastus muscle of runners and the deltoid muscle of swimmers contained 60% slow twitch fibres (ST) an none or few fast twitch b fibres (FTb). Otherwise the percentage of fibre types was 50% ST fibres, 30% to 35% FTa fibres, and 15% to 20% FTb fibres. In the lateral vastus muscle ST fibres wee larger than FT fibres, whereas in male skeletal muscles FT fibres tend to be larger than ST fibres. The capillarization was linearly related to maximal oxygen uptake, as is also the case in male subjects. The activity of biochemically determined phosphofructokinase (PFK) was the same in both muscles and in all groups; succinate dehydrogenase activity (SDH) was closely related to maximal oxygen uptake. Th activities of PFK and SDH were lower than in male subjects the ratio between the activities indicated that the relative contribution of oxidative metabolism was higher than in males. The morphological and biochemical differences between female and male skeletal muscle are found in sedentary and trained subjects, and may be due both to the influence of sex hormones, and to differences in the daily activity pattern.


Auxin receptors of maize coleoptile membranes do not have ATPase activity.
Membrane-localized auxin-binding sites from coleoptiles and primary leaves of Zea mays L. which may be auxin receptors can be fully solubilized by 1 to 1.5 mg of Triton X-100 per mg of membrane protein (about 1 mg per gram of original tissue fresh weight), while 70% of the basal (Mg(2+))-ATPase and 85% of the K(+)-stimulated (Mg(2+))-ATPase (pH 6) remain pelletable. Gel exclusion chromatography on Bio-Gel A-1.5m indicates that the solubilized receptors occur as detergent-protein micelles of about 90,000 daltons equivalent molecular weight. Solubilized ATPase activities occur (a) as very large particles excluded from the gel, and (b) as particles of a size substantially smaller than the particles that exhibit auxin binding. The auxin-binding receptor therefore appears not to be an ATPase.


A review of one hundred forty-seven popliteal aneurysms with long-term follow-up.
A 20-year experience with a collected series of 147 popliteal aneurysm in 87 patients is reviewed; there were 84 male patients. Ages ranged from 42 to 90 years with a median age of 60.2. Bilateral aneurysms were found in 60 patients (68%). Ninety-eight extremities presented with symptoms, whereas 94 aneurysms had one or more preoperative complications. Sixty-six (45%) were thrombosed, 34 (23%) had embolized, and four (3%) had ruptured. Associated aneurysms were found in 55% of the total group and in 68% of those with bilateral popliteal aneurysms. Forty percent of all patients had abdominal aortic aneurysms, whereas 34% had femoral aneurysms and 25% had iliac aneurysms. Therapy included bypass grafting (99), observations (26), primary amputation (12), sympathectomy (3), and exploration only (7). In 32 limbs, grafts became occluded during the follow-up period. All except one of the occluded grafts were in patients with preoperative symptoms related to the aneurysm, and all but one primary form of therapy and 22 as a secondary procedure. All were associated with preoperative vascular ischemia or a complicated aneurysm. Complete, detailed, long-term follow-up of 1 to 14 years is reported for 65 patients. The overall follow-up averaged 44 months. Death rates were shown by life-table analysis to be significantly greater than rates among the general population. Complications of aneurysms were very common (64%) and when the occurred, 36% ended in amputation. Therefore, elective replacement of the aneurysm at the time of diagnosis is recommended.


How Does Dung Beetle (Coleoptera: Scarabaeidae) Diversity Vary Along a Rainy Season in a Tropical Dry Forest?
Dung beetle community dynamics are determined by regional rainfall patterns. However, little is known about the temporal dynamics of these communities in tropical dry forests (TDFs). This study was designed to test the following predictions: 1) Peak diversity of dung beetle species occurs early in the wet season, with a decrease in diversity (α and β) and abundance throughout the season; 2) Nestedness is the primary process determining β-diversity, with species sampled in the middle and the end of the wet season representing subsets of the early wet season community. Dung beetles were collected in a TDF in the northern Minas Gerais state, Brazil over three sampling events (December 2009, February and April 2010). We sampled 2,018 dung beetles belonging to 39 species and distributed among 15 genera. Scarabaeinae α-diversity and abundance were highest in December and equivalent between February and April, while β-diversity among plots increased along the wet season. The importance of nestedness and species turnover varies between pairs of sample periods as the main process of temporal β-diversity. Most species collected in the middle and end of the wet season were found in greater abundance in early wet season. Thus, the dung beetle community becomes more homogeneous at the beginning of the wet season, and as the season advances, higher resource scarcity limits population size, which likely results in a smaller foraging range, increasing β-diversity. Our results demonstrate high synchronism between the dung beetle life cycle and seasonality of environmental conditions throughout the wet season in a TDF, where the onset of rains determines adult emergence for most species.


Self-tuning phase separation in a model with competing interactions inspired by biological cell polarization.
We present a theoretical study of a system with competing short-range ferromagnetic attraction and a long-range antiferromagnetic repulsion, in the presence of a uniform external magnetic field. The interplay between these interactions, at sufficiently low temperature, leads to the self-tuning of the magnetization to a value which triggers phase coexistence, even in the presence of the external field. The investigation of this phenomenon is performed using a Ginzburg-Landau functional in the limit of an infinite number of order parameter components (large N model). The scalar version of the model is expected to describe the phase separation taking place on a cell surface when this is immersed in a uniform concentration of chemical stimulant. A phase diagram is obtained as a function of the external field and the intensity of the long-range repulsion. The time evolution of the order parameter and of the structure factor in a relaxation process is studied in different regions of the phase diagram.


CsrA and Cra influence Shigella flexneri pathogenesis.
Shigella flexneri is a facultative intracellular pathogen that invades and disrupts the colonic epithelium. In order to thrive in the host, S. flexneri must adapt to environmental conditions in the gut and within the eukaryotic cytosol, including variability in the available carbon sources and other nutrients. We examined the roles of the carbon consumption regulators CsrA and Cra in a cell culture model of S. flexneri virulence. CsrA is an activator of glycolysis and a repressor of gluconeogenesis, and a csrA mutant had decreased attachment and invasion of cultured cells. Conversely, Cra represses glycolysis and activates gluconeogenesis, and the cra mutant had an increase in both attachment and invasion compared to the wild-type strain. Both mutants were defective in plaque formation. The importance of the glycolytic pathway in invasion and plaque formation was confirmed by testing the effect of a mutation in the glycolysis gene pfkA. The pfkA mutant was noninvasive and had cell surface alterations as indicated by decreased sensitivity to SDS and an altered lipopolysaccharide profile. The loss of invasion by the csrA and pfkA mutants was due to decreased expression of the S. flexneri virulence factor regulators virF and virB, resulting in decreased production of Shigella invasion plasmid antigens (Ipa). These data indicate that regulation of carbon metabolism and expression of the glycolysis gene pfkA are critical for synthesis of the virulence gene regulators VirF and VirB, and both the glycolytic and gluconeogenic pathways influence steps in S. flexneri invasion and plaque formation.


Multiple homogeneous immunoassays based on a quantum dots-gold nanorods FRET nanoplatform.
Multi-sized quantum dots (QDs) donors and tailor-made gold nanorods (GNRs) are employed to form a FRET nanoplatform for homogeneous immunoassays developed for analysis of multiple virus antigens. The single GNRs/multiple QDs nanocomposite based nanosensor offers a simple and sensitive approach for multiple analytes detection in a homogeneous format.


[Construction and expression of eucaryotic recombinant plasmid of Legionella pneumophila mip gene].
To construct recombinant plasmid of Legionella pneumophila mip gene and detect its expression in NIH3T3 cells. mip gene of Legionella pneumophila was amplified by PCR. The amplified DNA was ligated to pcDNA3.1(+) vector. The recombinant plasmid was named pcDNA3.1-mip. NIH3T3 cell was transfected by recombinant plasmid pcDNA3.1-mip with Lipofection strategy. Transient and stable products of mip gene were detected by immunofluorescence and Western-blot. It was found that there was high green fluorescence on the cell membrane and inside the cell. It showed that NIH3T3 cell was transfected by pcDNA3.1-mip successfully. Rabbit serum antibody of Legionella pneumophila detected the NIH3T3 cell transfected with pcDNA3.1-mip. There was the protein in relative molecular weight 24 X 10(3), whereas no evidence for the protein in NIH3T3 cell transfected with pcDNA3.1(+) was seen. The protein expression of mip gene was shown. We have successfully constructed the recombinant plasmid of Legionella pneumophila mip gene and detected the relative molecular weight 24 X 10(3) Mip protein in NIH3T3 cells.


The patterns of accumulation of cellular RNAs in cells infected with a wild-type and a mutant herpes simplex virus 1 lacking the virion host shutoff gene.
Cellular RNA extracted from quiescent human foreskin fibroblasts harvested at 1, 3, 7, or 12 h after infection was profiled on Affymetrix HG-U95Av2 arrays designed to detect 12,626 unique human transcripts. We also profiled RNA extracted from cells harvested at 1 and 7 h after infection with a mutant lacking the gene (DeltaU(L)41) encoding a protein (vhs) brought into cells by the virus and responsible for nonselective degradation of RNA early in infection. We report the following: (i) of the 12 tested genes, up-regulated at least 3-fold relative to the values of mock infected cells, 9 were confirmed by real-time PCR. The microchip assays analyses indicate that there were 475 genes up-regulated > or =3-fold. The up-regulated genes were clustered into 15 groups with respect to temporal pattern of transcript accumulation, and classified into 20 groups on the basis of their function. The preponderance of cellular genes up-regulated early in infection play a predominant role in transcription, whereas those up-regulated at later times respond to intracellular stress or concern themselves with the cell cycle and apoptosis. (ii) The number of genes up-regulated early in infection was higher in cells infected with the DeltaU(L)41 mutant. Conversely, more genes were down-regulated late in infection with wild-type virus than with mutant viruses. Both observations are compatible with the known function of the U(L)41 gene product early in infection and with degradation of cellular RNAs in the absence of replenishment by de novo transcription of cellular genes.


Novel pathway to synthesize unsymmetrical 2,3,9,10,16,17,23-heptakis(alkoxyl)-24-mono(dimethylaminoalkoxyl)phthalocyanines.
A new pathway by means of transetherification has been developed to synthesize novel unsymmetrical 2,3,9,10,16,17,23-heptakis(alkoxyl)-24-mono(dimethylaminoalkoxyl)phthalocyanine compounds. Cyclic tetramerization of 4,5-di(alkoxyl)phthalonitrile in refluxing dimethylamino-alcohol with high boiling point such as dimethylaminoethanol (DMAE) and 1-dimethylamino-2-propanol in the presence of lithium and pyrazino[2,3-f][1,10]phenanthroline-2,3-dicarbonitrile followed by treatment with acetic acid led to the isolation of a series of unsymmetrical metal free 2,3,9,10,16,17,23-heptakis(alkoxyl)-24-mono(dimethylaminoalkoxyl)phthalocyanine compounds H(2){Pc(OR)(7)[OR'N(CH(3))(2)]} [R = C(4)H(9), C(5)H(11), C(8)H(17) and R' = C(2)H(4); R = C(4)H(9) and R' = CH(CH(3))CH(2)] (1-4). Metal insertion into unsymmetrical metal free phthalocyanines (Pc's) using Cu(OAc)(2)·H(2)O in dimethylformamide (DMF) at 140 °C easily afforded corresponding unsymmetrical phthalocyaninato copper complexes Cu{Pc(OR)(7)[OR'N(CH(3))(2)]} (5-8) in good yields. These novel unsymmetrical phthalocyanine compounds have been characterized by a series of spectroscopic methods including (1)H NMR, electronic absorption, IR, and mass spectroscopy in addition to elemental analysis. Their electrochemistry was also studied by cyclic voltammetry (CV) and differential pulse voltammetry (DPV) methods. The present result will be helpful for designing and preparing unsymmetrical phthalocyanines with potential applications in dye-sensitized solar cells.


Effect of autonomic blockade on heart rate and blood pressure in sleep apnea syndrome.
To determine the impact of the autonomic nervous system on hemodynamic responses to sleep apnea we studied 7 male patients (48 +/- 6 years, BMI = 29.7 +/- 2.9 kg/m2) with an apnea index = 33 + 11/h. In two hypertensives, therapy was withdrawn 2 weeks before the study. During a full night polysomnography EEG, EOG, EMG, respiration, oximetry, heart rate (HR) and blood pressure (BP) (Finapres 23OOE) were recorded. Placebo and 3 short-acting autonomic blockers were randomly i.v. administered: antimuscarinic (atropine 1 mg, A), beta 1 blocker (esmolol 40 mg, E), alpha blocker (nicergoline 2.5 mg, N). A total of 367 obstructive apneas in NREM sleep were studied. With atropine, HR was increased at the beginning of apnea (P1)(74.5 +/- 2 bpm vs 65.4 +/- 2 bpm with placebo) and at the end apnea (P3) (76.6 +/- 1.9 bpm vs 67.1 +/- 1.76 bpm). At the resumption of breathing (RB), HR still increased (83.5 +/- 1.5 bpm vs 80.1 +/- bpm). Nicergoline had no significant effect on HR but significantly decreased SBP (117.8 +/- 1.4 mmHg vs 127 +/- 1.6 with placebo, p < 0.001). Nevertheless, the rise in BP from P3 to RB remained significant (p < 0.001). Esmolol significantly decreased HR at P1 (68.1 +/- 1.9 bpm vs 73.9 +/- 1.9 bpm) and at RB (75.9 +/- 1.9 vs 81.6 +/- 1.8). With A, the rise in HR at end-apnea (P3) suggests a vagal hyperactivity during this phase which is blunted at resumption when HR is unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)


Malignant bladder tumor transurethral resection in a patient with acquired C1 inhibitor deficiency.
Acquired C1-INH deficiency or acquired angiodema (AAE) is an uncommon cause of angiedema that can induce severe airway complications during surgical procedures. We present the perioperative management of a patient with AAE secondary to a malignant bladder tumor. Anesthetic guidelines could be useful in the management of this disorder.


Prostaglandin D2 and the role of the DP1, DP2 and TP receptors in the control of airway reflex events.
Prostaglandin D2 (PGD2) causes cough and levels are increased in asthma suggesting that it may contribute to symptoms. Although the prostaglandin D2 receptor 2 (DP2) is a target for numerous drug discovery programmes little is known about the actions of PGD2 on sensory nerves and cough. We used human and guinea pig bioassays, in vivo electrophysiology and a guinea pig conscious cough model to assess the effect of prostaglandin D2 receptor (DP1), DP2 and thromboxane receptor antagonism on PGD2 responses. PGD2 caused cough in a conscious guinea pig model and an increase in calcium in airway jugular ganglia. Using pharmacology and receptor-deficient mice we showed that the DP1 receptor mediates sensory nerve activation in mouse, guinea pig and human vagal afferents. In vivo, PGD2 and a DP1 receptor agonist, but not a DP2 receptor agonist, activated single airway C-fibres. Interestingly, activation of DP2 inhibited sensory nerve firing to capsaicin in vitro and in vivo. The DP1 receptor could be a therapeutic target for symptoms associated with asthma. Where endogenous PGD2 levels are elevated, loss of DP2 receptor-mediated inhibition of sensory nerves may lead to an increase in vagally associated symptoms and the potential for such adverse effects should be investigated in clinical studies with DP2 antagonists.


Unbound fraction of fluconazole and linezolid in human plasma as determined by ultrafiltration: Impact of membrane type.
Ultrafiltration is a rapid and convenient method to determine the free concentrations of drugs in plasma. Several ultrafiltration devices based on Eppendorf cups are commercially available, but are not validated for such use by the manufacturer. Plasma pH, temperature and relative centrifugal force as well as membrane type can influence the results. In the present work, we developed an ultrafiltration method in order to determine the free concentrations of linezolid or fluconazole, both neutral and moderately lipophilic antiinfective drugs for parenteral as well as oral administration, in plasma of patients. Whereas both substances behaved relatively insensitive in human plasma regarding variations in pH (7.0-8.5), temperature (5-37°C) or relative centrifugal force (1000-10.000xg), losses of linezolid were observed with the Nanosep Omega device due to adsorption onto the polyethersulfone membrane (unbound fraction 75% at 100mg/L and 45% at 0.1mg/L, respectively). No losses were observed with Vivacon which is equipped with a membrane of regenerated cellulose. With fluconazole no differences between Nanosep and Vivacon were observed. Applying standard conditions (pH 7.4/37°C/1000xg/20min), the mean unbound fraction of linezolid in pooled plasma from healthy volunteers was 81.5±2.8% using Vivacon, that of fluconazole was 87.9±3.5% using Nanosep or 89.4±3.3% using Vivacon. The unbound fraction of linezolid was 85.4±3.7% in plasma samples from surgical patients and 92.1±6.2% in ICU patients, respectively. The unbound fraction of fluconazole was 93.9±3.3% in plasma samples from ICU patients.


Public perceptions of arguments supporting and opposing recreational marijuana legalization.
In debates about recreational marijuana legalization, pro-legalization arguments highlighting economic and other potential policy benefits compete with anti-legalization arguments emphasizing public health risks. In 2016, we conducted a national survey using an online panel (N=979) designed to answer two main research questions: (1) How do Americans perceive the relative strength of competing arguments about recreational marijuana legalization? (2) How are perceptions of argument strength associated with public support for recreational marijuana legalization? We examined differences in attitudes among individuals living in states that have/have not legalized recreational marijuana and among Democrats/Independents/Republicans. Ordered logit regression assessed the relationship between perceived argument strength and public support for recreational marijuana legalization. Respondents rated pro-legalization arguments highlighting beneficial economic and criminal justice consequences as more persuasive than anti-legalization arguments emphasizing adverse public health effects. Respondents were more likely to agree with arguments highlighting legalization's potential to increase tax revenue (63.9%) and reduce prison overcrowding (62.8%) than arguments emphasizing negative consequences on motor vehicle crashes (51.8%) and youth health (49.6%). The highest rated anti-legalization arguments highlighted the conflict between state and federal marijuana laws (63.0%) and asserted that legalization will fail to eliminate the black market (57.2%). Respondents who endorsed pro-legalization economic and criminal justice arguments were more likely than other respondents to support legalization. Our findings indicate that, on both side of the recreational marijuana legalization debate, there are arguments that resonate with the American public. However, public health risk messages were viewed as less compelling than pro-legalization economic and criminal justice-oriented arguments.


Post-infectious acute renal failure due to calciphylaxis--when processes go the wrong way round.
Calciphylaxis is a rare life threatening disorder of small- and medium-sized vessel calcification that leads to cutaneous necrosis. While its pathogenesis is uncertain, nearly all cases have been described in patients with end-stage renal disease (ESRD) on dialysis or following renal transplantation which is why the lesion has also been referred to as calcific uremic arteriolopathy. We describe a patient with alcoholic cirrhosis and normal renal function who developed calciphylaxis. Due to infected cutaneous lesions, he developed an acute post-infectious glomerulonephritis with extra capillary proliferation.