[Demographic aging in Germany and the need for care in private households: a regional perspective].
"In the Federal Republic of Germany there are regional differences in the ageing process. As a result the increase of people needing care and attention differs regionally, too. The authors deal with the following questions: Which particular regions will be most affected by the ageing process and to which extent? How is the proportion of people needing care and those providing it in private households affected by this? To which extent can private households cope with the demands of nursing elderly people at home?" The focus is on the period 1992 to 2010. (SUMMARY IN ENG)


The effects of inhalational anesthetics on ischemic injury of rat kidney with renovascular occlusion.
The effects of halogenated inhalational anesthetics, viz. halothane, enflurane, isoflurane and sevoflurane, on ischemic rat kidneys were studied through the response of renal gamma-glutamyl transpeptidase in the brush border of proximal tubules to monoclonal antibodies. Brush border staining characteristics were evaluated as follows: a) continuous (normal), b) discontinuous (damaged) and c) indistinct (necrotic). The isoflurane group had significantly fewer damaged and/or necrotic proximal tubules compared to the other groups. These results suggest that isoflurane is the most appropriate inhalational anesthetic when renal circulation is impaired.


Comparison of the efficacy of direct coronary stenting with sirolimus-eluting stents versus stenting with predilation by intravascular ultrasound imaging (from the DIRECT trial).
A direct coronary stenting technique using drug-eluting stents may decrease drug-eluting stent efficacy due to possible damage to the surface coating of the stent. The DIRECT is a multicenter, prospective, nonrandomized trial designed to evaluate the direct stenting strategy for the sirolimus-eluting Bx-Velocity stent compared with the historical control (SIRIUS trial, stenting with predilation). Volumetric and cross-sectional intravascular ultrasound analyses at 8-month follow-up were performed in 115 patients (DIRECT n= 64, control n = 51). Patient and lesion characteristics were comparable between groups. The DIRECT group achieved an equivalent uniform expansion index, defined as minimum stent area/maximum stent area x 100, compared with the control group (65.9 +/- 11.7 vs 63.1 +/- 12.7, p = NS). At 8-month follow-up, vessel, stent, lumen, and neointimal volume index (volume in cubic millimeters/length in millimeters) and percent neointimal volume were similar between the DIRECT and control groups (vessel volume index 13.9 +/- 4.40 vs 15.0 +/- 3.83; stent volume index 6.83 +/- 2.02 vs 6.94 +/- 2.04; lumen volume index 6.71 +/- 2.04 vs 6.81 +/- 2.07; neointimal volume index 0.14 +/- 0.24 vs 0.16 +/- 0.23; percent neointimal volume 3.73 +/- 6.97 vs 3.14 +/- 5.32, p = NS for all). In addition, in-stent neointimal hyperplasia distribution was significantly smaller near the distal stent edge (0.22 vs 0.098 mm(3)/mm, p = 0.01 for an average neointimal volume index within 3 mm from the distal stent edge). In conclusion, direct coronary stenting with the sirolimus-eluting Bx-Velocity stent is equally effective in terms of uniform stent expansion and long-term quantitative intravascular ultrasound results compared with conventional stenting using predilation. This strategy appears to be associated with less neointimal hyperplasia near the distal stent edge.


Cabozantinib: A Review in Advanced Renal Cell Carcinoma.
The multiple tyrosine kinase inhibitor (TKI) cabozantinib (Cabometyx™) is approved in the USA for the treatment of patients with advanced renal cell carcinoma (RCC) who have received prior antiangiogenic therapy. In the EU, cabozantinib is indicated for the treatment of advanced RCC in adults following prior vascular endothelial growth factor (VEGF)-targeted therapy. In adults with advanced or metastatic clear-cell RCC who had previously received VEGF receptor (VEGFR) TKIs, progression-free survival (PFS) and overall survival (OS) were significantly prolonged in patients who received oral cabozantinib versus oral everolimus in the pivotal METEOR trial. Objective response was achieved in a significantly higher proportion of patients receiving cabozantinib than those receiving everolimus. Cabozantinib had a manageable adverse events profile in patients with advanced RCC. Thus, cabozantinib is an important new option for use in patients with advanced RCC who have previously received antiangiogenic therapy.


Biodistribution, dosimetry, and clinical evaluation of technetium-99m ethyl cysteinate dimer in normal subjects and in patients with chronic cerebral infarction.
Technetium-99m ethyl cysteinate dimer (ECD) has high initial cerebral uptake with slow clearance in nonhuman primates suggesting ideal characteristics for single photon emission computer tomography (SPECT) imaging. We evaluated the biodistribution, dosimetry and scintigraphic pattern of [99mTc]ECD in normal subjects and the accuracy of SPECT imaging in patients with chronic cerebral infarction. Sixteen normal subjects were injected with approximately 10 mCi of [99mTc]ECD. Anterior and posterior single-pass whole-body images were obtained at multiple times after injection. Blood clearance of the radiotracer was rapid, falling to 10.0 +/- 6.6% and 4.9 +/- 1.1% of the injected dose at 2 and 60 min, respectively. Brain uptake was 6.4 +/- 2.1% of the injected dose 5 min after injection. The critical organ was the urinary bladder. Technetium-99m ECD SPECT was performed with a rotating gamma camera in ten of the 16 normal subjects and 34 patients with clinical and CT evidence of chronic stroke. Thirty-three of the thirty-four patients had focal [99mTc]ECD abnormalities on SPECT (97.1%) based on visual inspection of the SPECT images. In summary, we obtained high quality SPECT images as a result of the optimal physical and biologic characteristics of the tracer. Technetium-99m ECD SPECT shows promise for the evaluation of patients with stroke.


The morphological and biomechanical changes of keratocytes cultured on modified p (HEMA-MMA) hydrogel studied by AFM.
The poor integration with host cornea tissue and the low mechanical properties of pHEMA hydrogel for artificial cornea remains a difficult problem to solve. A modified pHEMA hydrogel, MMA copolymerized and type-I collagen and bFGF immobilized, was previously prepared in an attempt to solve the problems. In this study, the cytotoxicity of Col/bFGF-p (HEMA-MMA) and p (HEMA-MMA) was studied by cell adhesion assay and atomic force microscopy (AFM). The results of cell adhesion assay show that the attachment of keratocytes on the modified membrane is much higher than that of the unmodified membrane. This indicates that the material after modification have better cell-material interaction. The AFM images reveal that the morphology of keratocytes cultured on different substrate is obviously different. The cell cultured on modified membrane presented a completely elongated and spindle-shape morphology. The force-distance indicates that the biomechanical of keratocytes changes significantly after culturing on different substrates. The adhesion force (2328+/-523 pN) and Young's modulus (0.51+/-0.125 kPa) of the cell cultured on modified membrane are much higher, and the stiffness (0.08+/-0.022 mN/m) is lower than those of the cell cultured on unmodified membrane. These results show that the cytotoxicity of Col/bFGF-p (HEMA-MMA) for keratocytes is much improved.


[Influence of Costimulatory Signaling Molecules on Immun Functons of B Lymphocytes in Patients with Immune Thrombocytopenia].
To explore the effect of costimulatory signaling molecules (CD80, CD86) expression on the quantity and function of B lymphocytes in peripheral blood (PB) of the patients with immune thrombocytopenia (ITP). A total of 55 ITP patients (30 cases were newly diagnosed and 25 cases were in remission), 25 healthy volunteers as controls were enrolled in this study. The levels of CD19(+)CD5(+), CD19(+)CD80(+), CD19(+)CD86(+), CD41a(+)IgG, CD41a(+)IgM and IgG, IgM in CD19(+)B cells were measured by flow cytometry (FCM). The correlation of CD19(+)B cells with clinical parameters of ITP patients was analyzed. The level of B1 (CD19(+)CD5(+)) of newly diagnosed ITP patients was significantly higher than that of remitted ITP patients and controls (P<0.05). The level of CD19(+)CD80(+) of newly diagnosed ITP patients was significantly higher than that of remitted ITP patients and controls (P<0.05). And the expression of IgG and IgM in CD19(+)B cells of newly diagnosed ITP patients was significantly higher than that of remitted ITP patients and controls (P<0.05). The levels of IgG and IgM in remitted ITP patients after treatment were significantly lower than that before treatment (P<0.05). The level differences of IgG and IgM before and after treatment in refractory ITP patients were not statistically significant (P>0.05). The expression of CD19(+)CD80(+) in newly diagnosed ITP patients positively correlated with the level of Th1 and Th1/Th2 (r=0.502, r=0.471, P<0.05). The expression of CD19(+)CD80(+) of newly diagnosed ITP patients positively correlated with the level of IgG and IgM in CD19(+)B cells (r=0.552, r=0.467, P<0.05), and negatively correlated with PB platelet count (r= -0.424, P<0.05). The levels of IgG and IgM in CD19(+)B cells of newly diagnosed ITP patients negati- vely correlated with PB platelet count (r=-0.658, r=-0.526, P<0.05). The enhacement of costimulatory signaling pathway of CD19(+)B cells in ITP patients results in the abnormal activation of B lymphocytes, thereby mediates the dysfunction of immune system and involves in the pathogenesis of ITP.


The 24-hour rhythm of blood pressure differs from that of leg hemodynamics in orthotopic heart transplant recipients.
This study was aimed at investigating whether a circadian rhythm of peripheral resistance exists in patients with orthotopic cardiac transplantation (OCT) and whether it parallels that of blood pressure (BP). BP and leg flow and resistance (plethysmography) were monitored for 24 hours in 13 denervated OCT recipients and 13 control patients with native heart, matched for casual blood pressure. On the basis of BP trend, control patients showed a BP reduction during sleep, whereas OCT recipients did not. Leg resistance was significantly lower and leg flow significantly higher during sleep than during waking in all patients, and the extent of the nocturnal decrease was similar in the two categories. The decrease in leg resistance in patients confined to bed for 24 hours is caused by peripheral mechanisms and does not depend on the autonomic control of the heart. The nocturnal decline in BP depends, on the contrary, on cardiac control and is lost in patients with denervated heart.


Evaluation of osseointegration of staged or simultaneously placed dental implants with nanocomposite fibrous scaffolds in rabbit mandibular defect.
Implant-supported dental prosthesis in patients with edentulism or those with reconstructed bone have long survival rate, but the success depends largely on the quality and quantity of the available bone at the recipient site. The usage of autograft is the gold standard treatment for vertical bone augmentation, but it has many limitations. In this study, we have developed a nanocomposite fibrous scaffold [silica coated nanoHA-gelatin reinforced with electrospun poly(L-lactic acid) (PLLA) nanoyarns] and evaluated its efficacy to promote osseointegration in rabbit mandibular defect in comparison to the scaffold without fibers and commercial nanoHA-collagen graft. For this, critical sized bilateral defect (10 mm length, 3 mm depth and 3 mm width) was created in rabbit mandible and dental implantation was done in two manners. In strategy 1, Ti dental implant was placed along with the scaffold and in strategy 2, the scaffold was implanted for 3 months to facilitate new bone formation followed by Ti dental implantation. In strategy 2, the fibrous scaffold could promote new bone formation and osseointegration in rabbit mandibular defect when compared to the scaffolds without fibers and commercial graft, but strategy 1 was not successful. These findings demonstrated that nanocomposite fibrous scaffold is a promising biomaterial to promote new bone formation and osseointegration in mandibular defect.


Doppler sonographic evaluation of arteriovenous shunt flow in a fetus with dural sinus malformation.
Dural sinus malformation (DSM) is a rare congenital malformation characterized by a dilated dural sinus pouch. We present a case of prenatally diagnosed DSM and propose a parameter to predict poor fetal outcome. Detailed ultrasonography at 26 weeks of our patient showed an intracranial cyst in the left posterior fossa. Color Doppler study indicated an arteriovenous shunt within the cyst with increased blood flow velocity. Based on these findings, fetal DSM with arteriovenous shunt was diagnosed. Because of fetal hydrops with high-output cardiac failure and maternal pregnancy-induced hypertension, labor was induced at 32 weeks and resulted in stillbirth. In conclusion, based on the present case, we can deduce that color Doppler study is useful for prenatal diagnosis of DSM with arteriovenous shunt and that a high-flow velocity to the cystic lesion is a possible predictor of hydropic change in such fetuses.


Isolation and biochemical characterization of two soluble iron(III) reductases from Paracoccus denitrificans.
Two soluble enzymes (FerA and FerB) catalyzing the reduction of a number of iron(III) complexes by NADH, were purified to near homogeneity from the aerobically grown iron-limited culture of Paracoccus denitrificans using a combination of anion-exchange chromatography (Sepharose Q), chromatofocusing (Mono P), and gel permeation chromatography (Superose 12). FerA is a monomer with a molecular mass of 19 kDa, whereas FerB exhibited a molecular mass of about 55 kDa and consists of probably two identical subunits. FerA can be classified as an NADH:flavin oxidoreductase with a sequential reaction mechanism. It requires the addition of FMN or riboflavin for activity on Fe(III) substrates. In these reactions, the apparent substrate specificity of FerA seems to stem exclusively from different chemical reactivities of Fe(III) compounds with the free reduced flavin produced by the enzyme. Observations on reducibility of Fe(III) chelated by vicinal dihydroxy ligands support the view that FerA takes part in releasing iron from the catechol type siderophores synthesized by P. denitrificans. Contrary to FerA, the purified FerB contains a noncovalently bound redox-active FAD coenzyme, can utilize NADPH in place of NADH, does not reduce free FMN at an appreciable rate, and gives a ping-pong type kinetic pattern with NADH and Fe(III)-nitrilotriacetate as substrates. FerB is able to reduce chromate, in agreement with the fact that its N-terminus bears a homology to the previously described chromate reductase from Pseudomonas putida. Besides this, it also readily reduces quinones like ubiquinone-0 (Q0) or unsubstituted p-benzoquinone.


Low-cost surface reconstruction for aesthetic results assessment and prediction in breast cancer surgery.
The high incidence and low mortality of breast cancer surgery has led to an increasing emphasis on the cosmetic outcome of surgical treatment. Advances in aesthetic evaluation, as well as surgical planning and outcome prediction, have been investigated by using geometrically precise 3D modelling of the breast surface prior to surgery and after the procedure. However, existing solutions are based on expensive site specific setups and remain weakly validated. In this paper, we explore the possibility of using low-cost RGBD cameras as an affordable and mobile system for breast surface reconstruction. The methodology relies on sensor calibration, uncertainty-driven point filtering, dense reconstruction and subsequent multi-view joint optimization to diffuse residual pose errors. Results from a phantom study, with ground truth obtained through commercially available scanners, indicate that the approach is promising with RMS errors in order of 2 mm. A clinical study shows the practical applicability of our method and compares favourably to high-end scanning solutions.


The influence of comorbidities on the aging males' symptoms scale in patients with erectile dysfunction.
To investigate if certain common age-related comorbidities are related with a positive aging males' symptoms (AMS) test outcome. This was a multicentric, transversal, observational study carried out in a male population with erectile dysfunction. Comorbidities and testosterone levels were registered. The relationship between comorbidities, testosterone levels, and the AMS test outcomes was studied using the global score and the sub-scale score components. The study included 1112 patients. In the multivariate analysis the global score strongly correlated with TT < 12 nmol/L (odds ratio [OR] = 3.17; p < 0.05), psychiatric disorders (OR = 2.73), dyslipidemia (OR = 2.07) and diabetes mellitus (OR = 1.64); the somatic sub-component was related to obesity (OR = 8.62), dyslipidemia (OR = 2.2) and TT < 12 nmol/L (OR = 2.09); the psychogenic sub-component correlated with psychiatric disorders (OR = 3.73), stress (OR = 2.42), dyslipidemia (OR = 1.78) and TT < 12 nmol/L (OR = 1.77); and the sexual sub-component was associated with high blood pressure (OR = 2.94). Although the AMS test is related to low levels of testosterone, it is also of some limited use for diagnosing hypogonadism because it has low specificity and is influenced by pathologies that are frequent during ageing.


A controlled trial of a 4-weekly supplement of rifampicin, pyrazinamide and streptomycin in the continuation phase of a 7-month daily chemotherapy regimen for pulmonary tuberculosis. Tanzania/British Medical Research Council Collaborative Investigation.
To evaluate a monthly 'pulse' of rifampicin plus pyrazinamide plus streptomycin in the continuation phase of a short-course antituberculosis regimen. Randomised controlled trial of two 7-month chemotherapy regimens. Inpatient chemotherapy and outpatient follow-up in Tanzania. Smear-positive pulmonary tuberculosis. All patients received streptomycin plus rifampicin plus isoniazid plus pyrazinamide daily for 6 weeks followed by isoniazid daily for 24 weeks; 50%, at random, received additional doses of rifampicin, pyrazinamide and streptomycin every 4 weeks in the continuation phase. Follow-up continued for 23 months after cessation of chemotherapy. Bacteriological failure rate at the end of chemotherapy and relapse rate after stopping. Of the 266 patients with fully sensitive strains before treatment there was one failure in each series during chemotherapy; after stopping, 5% of the 114 who received the supplement relapsed bacteriologically compared with 10% of the 113 who did not (95% CI for the difference -0.02% to + 11.3%). The results in the 37 patients with strains resistant to isoniazid pretreatment were not as good, but similar for the two regimens. This study was not large enough to demonstrate a significant reduction in the relapse rate from 10% to 5%. If such a reduction were confirmed in a larger study it would represent an important improvement in efficacy. further, in an outpatient setting, the additional monthly doses might improve attendance.


An Electropolymerized Crystalline Film Incorporating Axially-Bound Metalloporphycenes: Remarkable Reversibility, Reproducibility, and Coloration Efficiency of Ruthenium(II/III)-Based Electrochromism.
Oxidative electropolymeization of an axially bound, bithiophene-pyridine complex of ruthenium(III)-porphycene [Ru(TPrPc) (btp)2]PF6 (1) gives a submicrometer-thick, polymeric film on an ITO electrode with a crystalline morphology. The polymeric film, the first example of axially linked multimetalloporphycene coordination arrays, exhibits highly stable and reproducible electrochromic response with high electrochromic efficiency upon electrochemical control over the metal-centered electron transfer process (Ru(II)/Ru(III)).


Recent Issues in the Use of Signed Language Assessments for Diagnosis of Language Disorders in Signing Deaf and Hard of Hearing Children.
In recent years, normed signed language assessments have become a useful tool for researchers, practitioners, and advocates. Nevertheless, there are limitations in their application, particularly for the diagnosis of language disorders, and learning disabilities. Here, we discuss some of the available normed, signed language assessments and some of their limitations. We have also provided information related to practices that should lead to improvement in the quality of signed language assessments.


EGFR somatic doublets in lung cancer are frequent and generally arise from a pair of driver mutations uncommonly seen as singlet mutations: one-third of doublets occur at five pairs of amino acids.
Doublet mutations in cancer are not well studied. We find that allelic somatic doublet mutations are present at high frequency in the epidermal growth factor receptor (EGFR) tyrosine kinase (TK) domain in lung cancers. When doublets from the literature are added, a total of 96 doublets are available for analysis. The frequency of doublets overall is 6%, which is sevenfold greater than that observed in normal tissue in mouse. All characterized doublets are allelic, and silent mutations occur rarely. About half of all doublets contain one or two of 12 distinct missense mutations at five amino acids: E709, G719, S768, T790 and L861. The mutations at these five amino acids are seldom reported as singlets. Moreover, when the common L858 target is included, more than one-third of EGFR doublets are one of five specific missense pairs: G719/E709, G719/S768, G719/L861, L858/E709 and L858/T790. Structure suggests function: The data imply that most EGFR doublets are NOT consistent with a 'driver and passenger' mutation mechanism. EGFR doublets are highly skewed relative to singlets, consistent with functional selection of two individually suboptimal mutations that, in combination, have enhanced oncogenic potential.


[New direct restorative materials].
People worldwide have become increasingly aware of the potential adverse effects on the environment, of pollution control and of toxic effects of food, drugs and biomaterials. Amalgam and its potential toxic side effects (still scientifically unproven) continue to be discussed with increasing controversy by the media in some countries. Consequently, new direct restorative materials are now being explored by dentists, materials scientists and patients who are searching for the so-called 'amalgam substitute' or 'amalgam alternative'. From a critical point of view some of the new direct restorative materials are good with respect in aesthetics, but all material characteristics must be considered, such as mechanical properties, biological effects, and longterm clinical behaviour.


VEGFR-2, CXCR-2 and PAR-1 germline polymorphisms as predictors of survival in pancreatic carcinoma.
Hypoxic environment of pancreatic cancer (PC) implicates high vascular in-growth, which may be influenced by angiogenesis-related germline polymorphisms. Our purpose was to evaluate polymorphisms of vascular endothelial growth factor receptor 2 (VEGFR-2), CXC chemokine receptor 2 (CXCR-2), proteinase-activated receptor 1 (PAR-1) and endostatin (ES) as prognostic markers for disease-free (DFS) and overall survival (OS) in PC. Genotyping of 173 patients, surgically treated for PC between 2004 and 2011, was carried out by TaqMan(®) genotyping assays or polymerase chain reaction. Chi-square test, Kaplan-Meier estimator and Cox regression hazard model were used to assess the prognostic value of selected polymorphisms. VEGFR-2 -906 T/T and PAR-1 -506 Del/Del genotypes predicted longer DFS (P = 0.003, P = 0.014) and OS (VEGFR-2 -906, P = 0.011). CXCR-2 +1208 T/T genotype was a negative predictor for DFS (P < 0.0001). Combined analysis for DFS and OS indicated that patients with the fewest number of favorable genotypes simultaneously present (VEGFR-2 -906 T/T, CXCR-2 +1208 C/T or C/C and PAR-1 -506 Del/Del) were at the highest risk for recurrence or death (P < 0.0001). VEGFR-2 -906 C>T, CXCR-2 +1208 C>T and PAR-1 -506 Ins/Del polymorphisms are potential predictors for survival in PC.


Cloning of an apamin binding protein of vascular smooth muscle.
The receptor for the bee venom derived neurotoxin, apamin, is widely believed to be an integral component of the small conductance calcium-activated potassium channel in many excitable cells. By affinity chromatography on immobilized apamin, a 78 kD apamin binding protein of the bovine brain synaptosomes was isolated. Antibodies were elicited against this protein and used to clone a cDNA from a porcine vascular smooth muscle expression library. This gene (Kcal 1.8) codes for a 438 amino protein with four potential transmembrane domains, one putative calcium binding site, a protein kinase C phosphorylation site, and a leucine zipper motif. Kcal 1.8 encoded protein has no significant sequence homologies with any known ion channels or receptors. Kcal 1.8 is likely to encode a protein associated with the small conductance calcium-activated potassium channel in vascular smooth muscle.


A revised structure of the antitumor drug elliptinium--amino(acid) adducts.
Using simple organic reactions and spectrometric techniques (nuclear magnetic resonance and mass spectrometry), we propose a revised structure of the adducts obtained through the H2O2-peroxidase oxidation of the antitumor drug ellipticinium and aliphatic amino(acid) compounds. These derivatives display an oxazole ring structure between the O(9)- and N(10)- atoms.


Fragrance material review on ethyl hexyl salicylate.
A toxicologic and dermatologic review of ethyl hexyl salicylate when used as a fragrance ingredient is presented.


Synthesis of analogs of K-582A, an antibiotic heptapeptide.
K-582 A, an antibiotic heptapeptide, has a sequence of H-L-Arg-L-Arg(OH)-D-Orn-L-Thr-D-Orn-L-Lys-D-Tyr-OH (Arg(OH), threo-gamma-hydroxyarginine). In order to investigate the relationship between structure and antimicrobial activity, four shortened analogs, des-L-Arg1, L-Arg(OH)2-K582 A (pentapeptide), des-L-Arg(OH)2-K-582 A (hexapeptide) and their N-acetyl derivatives, were synthesized by the conventional method. None of them, however, showed any antimicrobial activity. Three more analogs, [L-Lys2]K-582 A, [L-Orn2]K-582 A and [L-Arg2]K-582 A, were synthesized. Among them, only [L-Arg2]K-582 A showed substantial activity against Candida krusei and Saccharomyces rouxii, indicating that the presence of a guanidyl side chain at position 2 is an essential factor for the induction of activity.


[The use of fluconazole in low-weight neonates with candidiasis].
Systemic Candida Albicans infections in premature newborns are characterized by high morbidity; early diagnosis and immediate treatment are therefore necessary. In this study we report the cases of fourteen newborns admitted to our Newborn Care Unit in a three-year period, in whom candidiasis was diagnosed. The mycetes was isolated from blood, liquor, peritoneal fluid, urine, oesophageal aspirate. Treatment was undertaken immediately with fluconazole, administered through the parenteral route or locally into peritoneal cavum and oesophageal stump. Duration of treatment varied from five to twenty-one days. All cases underwent complete negativization of cultures and no systemic or local side effects.


German healthcare professionals' perspective on implementing recommendations about polypharmacy in general practice: a qualitative study.
Key recommendations for the management of patients with polypharmacy are structured medication counselling (SMC), medication lists and systematic medication reviews. The aim of this study was to identify determinants (hindering and facilitating factors) for the implementation of the recommendations in general practice. This study was linked to a tailored intervention aimed at improving the implementation of the recommendations in German general practice. Interviews and focus groups with different healthcare professionals were carried out in the design phase and after delivery of the intervention. The material from both data collections was analysed separately in a content analytical approach resulting in two sets of categories. For this study, the subcategories of both sets were assigned to the Tailoring Interventions for Chronic Diseases (TICD) checklist, a comprehensive framework of determinants of practice. Interviews with 24 general practitioners (GPs), 4 other medical specialists, 1 pharmacist, 3 nurses and 6 medical assistants as well as 2 mixed focus groups with 17 professionals were conducted. We identified 93 determinants: 29 referred to medication counselling, 21 to the use of medication lists, 20 to medications reviews and 23 to all recommendations. The determinants were related to all 7 main domains and to 25 of the 57 subdomains on the TICD checklist including guideline factors, patient factors, individual healthcare professional factors, social, political and legal factors, incentives and resources, and capacity for organizational change. While many interventions to improve polypharmacy focus on the provision of pharmacological knowledge, a much wider range of domains need to be addressed, such as communication skills, patient involvement and practice organization.


[Infectious complications postengrafment in the first year after autologous stem cell transplantation in children].
Studies on the infectious complications postengrafment in pediatric stem cell transplantation patients are rare. The aim of this study was to assess the incidence, types, outcome and factors affecting late infections. A single-institution retrospective analysis was done of infections recorded in the first year following engrafment in children who underwent autologous stem cell transplantation for solid tumors from January 1991 to December 2000. A systematic antimicrobial chemoprophylaxis of TMP/SMX was administered. Patients who were at high risk for varicella-zona virus infection received prophylactic acyclovir. Eighty-four assessable patients were enrolled. Fifty-four patients (64%) underwent autologous peripheral blood stem cell transplantation and 30 patients (36%) underwent bone marrow transplantation. Forty-nine episodes of infections were documented in 39 patients (46%) of whom 27 patients (32%) developed infections after the first 100 days post transplantation. Bacterial septicemia occurred in nine patients of whom four patients had a catheter-related septicemia. Twelve patients (14%) developed localized herpes zoster infection. Local fungal infection occurred in five patients. Infection-related death occurred in one patient with non-documented pneumonitis. Univariable analysis showed a correlation between the CD34(+) cell dose <7.5 10(6)/kg and the development of infections (P =0.04). Patients who did not go into remission after transplantation where at high risk for septicemia (P =0.007). Multivariate analysis showed that a history of varicella or pretransplant varicella-zona positivity was the only significant factor for development zoster infection (P =0.01). Our study shows that infections in the first year postengrafment following autologous stem cell transplantation for solid tumors have a good prognosis and that the use of TMP/SMX should be the single systematic antimicrobial prophylaxis. The CD34(+) cell dose seems to play a role in preventing late infections.


Differential capacity of left and right hemispheric areas for compensation of poststroke aphasia.
As previous functional neuroimaging studies could not settle the controversy regarding the contribution of dominant and subdominant hemisphere to recovery from poststroke aphasia, language performance was related to H2(15)O-positron emission tomographic activation patterns in 23 right-handed aphasic patients 2 and 8 weeks after stroke. In patients classified according to the site of lesion (frontal, n = 7; subcortical, n = 9; temporal, n = 7) and in 11 control subjects, flow changes caused by a word repetition task were calculated in 14 regions representing eloquent and contralateral homotopic areas. These areas were defined on coregistered magnetic resonance imaging scans and tested for significance (Bonferroni corrected t test, alpha = 0.0036). At baseline, differences in test performance were only found between the subcortical and temporal group. The extent of recovery, however, differed and was reflected in the activation. The subcortical and frontal groups improved substantially; they activated the right inferior frontal gyrus and the right superior temporal gyrus (STG) at baseline and regained left STG activation at follow-up. The temporal group improved only in word comprehension; it activated the left Broca area and supplementary motor areas at baseline and the precentral gyrus bilaterally as well as the right STG at follow-up, but could not reactivate the left STG. These differential activation patterns suggest a hierarchy within the language-related network regarding effectiveness for improvement of aphasia; ie, right hemispheric areas contribute, if left hemispheric regions are destroyed. Efficient restoration of language is usually only achieved if left temporal areas are preserved and can be reintegrated into the functional network.


Effects of high-flux hemodialysis on oxidant stress.
Neutrophil oxygen radical production is increased in end-stage renal disease (ESRD) patients and it is further enhanced during dialysis with low-flux cellulosic membranes. This increased oxygen radical production may contribute to the protein and lipid oxidation observed in ESRD patients. We tested the hypothesis that high-flux hemodialysis does not increase oxygen radical production and that it is not associated with protein oxidation. Neutrophil oxygen radical production was measured during dialysis with high-flux dialyzers containing polysulfone and cellulose triacetate membranes. Free sulfhydryl and carbonyl groups and advanced oxidation protein products were measured to assess plasma protein oxidation. Pre-dialysis, neutrophil oxygen radical production was significantly greater than normal and increased significantly as blood passed through the dialyzer in the first 30 minutes of dialysis. Post-dialysis, however, neutrophil oxygen radical production had decreased and was not different from normal. Pre-dialysis, significant plasma protein oxidation was evident from reduced free sulfhydryl groups, increased carbonyl groups, and increased advanced oxidation protein products. Post-dialysis, plasma protein free sulfhydryl groups had increased to normal levels, while plasma protein carbonyl groups increased slightly, and advanced oxidation protein products remained unchanged. The results of this study show that neutrophil oxygen radical production normalizes during high-flux dialysis, despite a transient increase early in dialysis. This decrease in oxygen radical production is associated with an improvement in some, but not all, measures of protein oxidation.


Imaging genetics approach to predict progression of Parkinson's diseases.
Imaging genetics is a tool to extract genetic variants associated with both clinical phenotypes and imaging information. The approach can extract additional genetic variants compared to conventional approaches to better investigate various diseased conditions. Here, we applied imaging genetics to study Parkinson's disease (PD). We aimed to extract significant features derived from imaging genetics and neuroimaging. We built a regression model based on extracted significant features combining genetics and neuroimaging to better predict clinical scores of PD progression (i.e. MDS-UPDRS). Our model yielded high correlation (r = 0.697, p <; 0.001) and low root mean squared error (8.36) between predicted and actual MDS-UPDRS scores. Neuroimaging (from 123I-Ioflupane SPECT) predictors of regression model were computed from independent component analysis approach. Genetic features were computed using image genetics approach based on identified neuroimaging features as intermediate phenotypes. Joint modeling of neuroimaging and genetics could provide complementary information and thus have the potential to provide further insight into the pathophysiology of PD. Our model included newly found neuroimaging features and genetic variants which need further investigation.


Cosmosperma polyloba gen. et sp. nov., a seed plant from the Upper Devonian of South China.
Seed plants with ovules were abundant in the Late Devonian of Euramerica and they contribute significantly to our understanding of their early history. However, coeval ovules have been scarce in other regions of the world. Specimens of the seed plant Cosmosperma polyloba gen. et sp. nov. Wang et al. were recently obtained from the Upper Devonian (Famennian) Wutong Formation, at Fanwan Village, Changxing County, Zhejiang Province, China. This new seed plant has cupulate ovules, the uniovulate cupules with up to 16 distal segments and with minute spines on the outer surface, synangiate pollen organs bearing six to eight microsporangia fused only at the base, and planate and highly dissected pinnules in alternate arrangement. It differs from other Devonian seed plants mainly in the organization and position of the uniovulate and ornamented cupule, and in the highly dissected pinnules. Cosmosperma Wang et al. represents the first Devonian ovules recovered from China or eastern Asia and further illustrates the diversity of early spermatophytes. As for the Late Devonian seed plants, it is suggested that the pollen organs are synangiate and simple in organization, and the branches and leaves are generally planate.


[The thermoregulatory effectiveness of calcitonin in progressive scleroderma].
During a 10-day hospitalization, 21 patients suffering from systemic sclerosis (SS) with Raynaud's phenomenon were treated intermittently with intravenous infusions of calcitonin for 5 hours daily. Telethermographically, we measured a significantly shortened rewarming period of the patients' hand after standardized cooling. Up to now, as many as 47 patients with SS have been treated in the same way during 152 10-day cycles of calcitonin infusion. Only 7 patients interrupted the calcitonin therapy because of transient headache or nausea. Allergic reactions have not been observed, so far.


Solution structure and backbone dynamics of the XPC-binding domain of the human DNA repair protein hHR23B.
Human cells contain two homologs of the yeast RAD23 protein, hHR23A and hHR23B, which participate in the DNA repair process. hHR23B houses a domain (residues 277-332, called XPCB) that binds specifically and directly to the xeroderma pigmentosum group C protein (XPC) to initiate nucleotide excision repair (NER). This domain shares sequence homology with a heat shock chaperonin-binding motif that is also found in the stress-inducible yeast phosphoprotein STI1. We determined the solution structure of a protein fragment containing amino acids 275-342 of hHR23B (termed XPCB-hHR23B) and compared it with the previously reported solution structures of the corresponding domain of hHR23A. The periodic positioning of proline residues in XPCB-hHR23B produced kinked alpha helices and assisted in the formation of a compact domain. Although the overall structure of the XPCB domain was similar in both XPCB-hHR23B and XPCB-hHR23A, the N-terminal part (residues 275-283) of XPCB-hHR23B was more flexible than the corresponding part of hHR23A. We tried to infer the characteristics of this flexibility through (15)N-relaxation studies. The hydrophobic surface of XPCB-hHR23B, which results from the diverse distribution of N-terminal region, might give rise to the functional pleiotropy observed in vivo for hHR23B, but not for hHR23A.


Penetration of topical cyclosporine into the rabbit cornea, aqueous humor, and serum.
Systemic and ocular absorption of topically applied 10% cyclosporine ointment was determined in rabbit cornea, aqueous humor, and serum by radioimmunoassay. The concentration of the drug in the cornea reached a peak of 900 ng/mL three hours after application. Substantial levels were still present at 24 hours. Relatively low concentrations were measured in the aqueous humor and serum, suggesting corneal stromal pooling of this hydrophobic cyclic peptide. Topical ocular application of cyclosporine may reduce or eliminate the drug's systemic toxic effects while maintaining a therapeutic level of local immunosuppressive activity.


[Vertebral body augmentation using a vertebral body stent].
Osteoporotic vertebral fractures can be treated by minimally invasive percutaneous vertebral augmentation with bone cement using vertebroplasty or balloon kyphoplasty. Transcutaneous reduction and vertebral body stenting has been the most recent principle. In contrast to balloon placement in kyphoplasty, the stent remains in the vertebral body and supports both the vertebral body and cement filling. In this retrospective study we present the essential information on the method and our first results. The method of vertebral body stent placement was used in 22 patients treated at 29 levels. Of these, 19 patients with 26 segments followed up for 3 months were evaluated. The group included 12 women and seven men with an average age of 68.3 years (12 to 83). The patients assessed their subjective complaints on the visual analogue scale (VAS) before surgery, and then at 1, 6 and 12 weeks post-operatively. The value of vertebral body reduction was obtained by measurement of anterior, middle and posterior vertebral body heights (AVBH, MVBH and PVBH, respectively) and a change in the vertebral body kyphotic angle (VBKA). Twenty-four vertebrae were treated for osteoporotic fracture and two as preventive stenting in metastatic breast cancer. In 24 fractures, the stents extended fully in 20 vertebrae, i.e., 40 stents. These fractures evidently were not older than 3 months. In four segments, a total of eight stents did not extend at all or did only slightly. The 20 stabilised vertebral bodies had an average AVBH value of 19.41 mm pre-operatively and that of 22.775 mm post-operatively, which is an average increase by 3.365 mm in absolute numbers and by 17.34 %. The average pre- and post-operative MVBH values were 16.625 mm and 23.065 mm, which was improvement by 6.41 mm or by 38.56 %. The average PVBH values pre- and post-operatively were 26.835 mm and 28.31 mm, which meant improvement by 1.475 mm or by 5.5 %. The average correction of the kyphotic angle was 4.58°, i.e., 35.2 %, from a VBKA of 11.71° pre-operatively to 7.13° post-operatively. There were five cases (22.7 %) of cement leakage, i.e., two of ventral leakage, one of lateral leakage, one of dorsal leakage through a canal left in the pedicle by cannula insertion, and a dorsal leakage in metastatic disease. No neurological findings were recorded. The average VAS scores were as follows: 81.4 before surgery, 30.6 at 1 week, 16.3 at 6 weeks and 15.4 at 12 weeks after surgery. Two experimental and one clinical study on vertebral body stenting only have been available in the recent relevant literature. In comparison with their results as well as with those of previous reports on vertebroplasty and kyphoplasty, our results showed high quality fracture reduction in all vertebrae. The rapid decrease in pain intensity in our group is comparable with all available groups treated by any method of vertebral body augmentation by cement injection; and cement leakage was recorded in even fewer cases. The novel method of vertebral body stenting with cement augmentation provides a rapid pain relief, gives stability to fracture reduction and has a low rate of cement leakage. However, care must be taken not to indicate cases with a damaged posterior corticalis of the vertebral body.


Enzyme-mediated site-specific bioconjugation of metal complexes to proteins: sortase-mediated coupling of copper-64 to a single-chain antibody.
The enzyme-mediated site-specific bioconjugation of a radioactive metal complex to a single-chain antibody using the transpeptidase sortase A is reported. Cage amine sarcophagine ligands that were designed to function as substrates for the sortase A mediated bioconjugation to antibodies were synthesized and enzymatically conjugated to a single-chain variable fragment. The antibody fragment scFv(anti-LIBS) targets ligand-induced binding sites (LIBS) on the glycoprotein receptor GPIIb/IIIa, which is present on activated platelets. The immunoconjugates were radiolabeled with the positron-emitting isotope (64)Cu. The new radiolabeled conjugates were shown to bind selectively to activated platelets. The diagnostic potential of the most promising conjugate was demonstrated in an in vivo model of carotid artery thrombosis using positron emission tomography. This approach gives homogeneous products through site-specific enzyme-mediated conjugation and should be broadly applicable to other metal complexes and proteins.


Increase of EEG Alpha3/Alpha2 Power Ratio Detects Inferior Parietal Lobule Atrophy in Mild Cognitive Impairment.
The inferior parietal lobule (IPL) has been implicate in many higher cognitive processes, as visuo-motor transformations, tool use or tool making. In subjects with mild cognitive impairment (MCI) at major risk to develop Alzheimer' Disease (AD) an impairment of subtle visuomotor or praxic abilities is a well-known clinical feature. Enhance of the ratio of EEG alpha3/alpha2 frequency power was detected in subjects with MCI who will transform in Alzheimer's disease (AD). We explored of the association of alpha3/alpha2 power ratio with cortical size of IPL in patients with MCI. 74 subjects with MCI undergone EEG recording and MRI scans. Alpha3/alpha2 power ratio in addition to cortical size had been computed for each patient. Three MCI groups had been acquired in keeping with growing tertile values of alpha3/alpha2 ratio. Huge difference of cortical thickness among the groups was calculated. Higher alpha3/alpha2 power ratio group had broader cortical loss compared to other teams on the IPL, particularly in the Supramarginal Gyrus, and Precuneus on both hemispheres. Our results unveil the possible part that the IPL could play in determining the classic alterations of early Alzheimer's disease (AD). Finally, the rise of alpha3/alpha2 power ratio detected a focused anatomo-functional association that could be a reliable marker of incipient AD.


Fatigue and extended work hours among cardiovascular perfusionists: 2010 Survey.
Due to the emergent unpredictable nature of cardiac surgery, perfusionists, potentially, are susceptible to extended work hours and acute sleep deprivation. While fatigue among other healthcare clinicians has been studied, there has been no research on this topic specifically in the perfusion community. Therefore, the purpose of this study was to: (1) collect preliminary data on the prevalence of fatigue in perfusion and (2) identify if there were concerns regarding fatigue, performance and perfusion safety. In May 2010, a link to a 50-question survey (surveymonkey.com) was posted on Perflist and Perfmail. The survey was closed in July 2010. There were 445 respondents and data were analyzed and expressed as a response percent. Participants included 27% chief perfusionists/managers, 67% staff perfusionists, and 6.0% other (perfusion education faculty, retired perfusionists, locum tenens). Regarding extended work hours, 68.9% of surveyed perfusionists have worked at the hospital for greater than 23 hours straight and 17.5% have worked continuously for over 36 hours. Actual performance of cardiopulmonary bypass (CPB) after 17, 23, and 36 hours of wakefulness was reported by 82.9%, 63% and 14.8% respondents, respectively. Regarding bathroom requirements while on CPB, 87.5% have felt extremely uncomfortable at least once, 19.9% have relieved themselves in the operating room at least once, and 22.3% have left the pump attended by a non-perfusionist to use the restroom at least once. Microsleep during CPB was reported by 49.5% of respondents. Automobile accidents attributed to an extended period of work and fatigue was reported by 6.9% and another 44.4% reported a near-miss auto accident. A fatigue-related minor error was reported by 66% and 6.7% admit to having a serious perfusion accident believed to be due to fatigue. Concerning critical phases of bypass, 51.5% believe that they perform less effectively when fatigued. Additionally, 75.9% indicate that they have been concerned about their ability to perform their job adequately due to fatigue-related acute sleep deprivation. Opinions regarding workplace management were as follows; 48% believe that fatigue can play a role in our profession and managers should do what they can to provide a rested staff, but, unfortunately, it is impractical to set work limits; 32.2% believe fatigue issues should be taken more seriously and specific guidelines should be stated by our professional organizations and 13.4% believe that limits should be established, legislated, and enforced by state or federal authorities. Based upon this preliminary survey data, it appears that fatigue and acute sleep deprivation is a significant safety concern in the perfusion community. Further research must be performed to understand actual performance degradation that may occur in fatigued perfusionists performing CPB.


Invariant Recognition Shapes Neural Representations of Visual Input.
Recognizing the people, objects, and actions in the world around us is a crucial aspect of human perception that allows us to plan and act in our environment. Remarkably, our proficiency in recognizing semantic categories from visual input is unhindered by transformations that substantially alter their appearance (e.g., changes in lighting or position). The ability to generalize across these complex transformations is a hallmark of human visual intelligence, which has been the focus of wide-ranging investigation in systems and computational neuroscience. However, while the neural machinery of human visual perception has been thoroughly described, the computational principles dictating its functioning remain unknown. Here, we review recent results in brain imaging, neurophysiology, and computational neuroscience in support of the hypothesis that the ability to support the invariant recognition of semantic entities in the visual world shapes which neural representations of sensory input are computed by human visual cortex.


Dakin solution alters macrophage viability and function.
Macrophages are important in wound defense and healing. Dakin's solution (DS), buffered sodium hypochlorite, has been used since World War I as a topical antimicrobial for wound care. DS has been shown to be toxic to host cells, but effects on immune cells are not well documented. DS at 0.5%, 0.125%, and ten-fold serial dilutions from 0.25%-0.00025% were evaluated for cellular toxicity on murine macrophages (J774A.1). The effect of DS on macrophage adhesion, phagocytosis, and generation of reactive oxygen species was examined. Macrophage polarization following DS exposure was determined by gene expression using quantitative real-time polymerase chain reaction. Concentrations of DS >0.0025% reduced macrophage viability to <5% in exposure times as short as 30 s. Similarly, phagocytosis of Staphylococcus aureus, Pseudomonas aeruginosa, and Aspergillus flavus were significantly reduced at all tested concentrations by macrophages pretreated with DS. H2O2 production was reduced by 8%-38% following treatment with 0.00025%-0.125% DS. Macrophage adherence was significantly increased with >0.0025% DS after 15 min of exposure compared with controls. Quantitative real-time polymerase chain reaction demonstrated that DS exposure resulted in classical macrophage activation, with increased expression of inducible nitric oxide synthase 2, interferon-γ, and interleukin (IL)-1β. DS at clinically used concentrations (0.025%-0.25%) was detrimental to macrophage survival and function. For optimal clinical use, understanding the impact of DS on macrophages is important as depletion may result in impaired pathogen clearance and delayed healing. These findings indicate that 0.00025% DS is a safe starting dose; however, optimal use of DS requires further validation with in vivo models.


Gains of 13q are correlated with a poor prognosis in liposarcoma.
Liposarcomas are a phenotypical heterogeneous group of tumors divided into four main subtypes: well-differentiated, dedifferentiated, myxoid/round cell, and pleomorphic. The aim of this study was to compare DNA sequence copy number changes of these subtypes as investigated by comparative genomic hybridization in 36 patients. Comparative genomic hybridization revealed genomic imbalances in tumors of 27 patients (mean 5.6 imbalances per tumor). The most frequent gains were within single regions of 1q, 12q, and 13q. We found a significant correlation of poor overall survival and gain of 13q21 (P=0.0221), 13q22 (P=0.0341), 13q31 (P=0.0410), and 13q32 (P=0.0074). The univariate Cox regression analysis revealed an increased risk of tumor-related death for patients whose liposarcomas possess with gains of 13q21 and 13q32 simultaneously (P=0.010; RR=7.1; 95% CI 1.6-31.7). Furthermore, 12 high-level amplifications were found in tumors of seven patients. In four cases 12q14-q15 and in two cases 13q32-q33 were amplified. We identified in different liposarcoma subtypes characteristic genomic changes: Gains and high-level amplifications of 12q occurred in all 11 investigated well-differentiated liposarcomas, and these changes were often present simultaneously with gains of 1q (mean 5.5 changes). In the two dedifferentiated liposarcomas, gains of 1q in both liposarcomas, and a high-level amplification of 13q were striking. Only eight of the 17 patients with myxoid/round cell liposarcomas showed changes in DNA copy number (mean 3.4 imbalances). In four of these eight cases gains of 13q occurred. The six pleomorphic liposarcomas possessed the most frequent genomic imbalances (mean number 16.3) of all liposarcoma subtypes investigated. These imbalances were in almost all chromosomal regions detected predominantly as over-representations of chromosomes 1, 5p, 13q, and 22q. Summarizing, all subtypes but well-differentiated liposarcomas showed gains of 13q, which were associated with a poor prognosis.


Development of a process for large-scale purification of C-phycocyanin from Synechocystis aquatilis using expanded bed adsorption chromatography.
In this paper a large and scaleable method for purification of C-phycocyanin (C-PC) from the cyanobacteria Synechocystis aquatilis has been developed. Phycobiliproteins are extracted from the cells by osmotic shock and separated by passing the centrifuged cell suspension through an expanded bed adsorption chromatography (EBAC) column using Streamline-DEAE as adsorbent. The eluted C-PC rich solution is finally purified by packed-bed chromatography using DEAE-cellulose. Optimal extraction is achieved using phosphate 0.05 M buffer pH 7.0 twice. The operation of EBAC is optimized on a small scale using a column of 15 mm internal diameter (I.D.). The optimal conditions are a sample load of 4.9 mg C-PC/mL adsorbent, an expanded bed volume twice the settled bed volume and a sample viscosity of 1.020 mP. The EBAC process is then scaled up by increasing the column I.D. (15, 25, 40, 60 and 90 mm) and the success of the scale-up process is verified by determining the protein breakthrough capacity and product recovery. The yield of the EBAC step is in the range of 90-93% for every column diameter. To obtain pure C-PC, conventional ion-exchange chromatography with DEAE-cellulose is utilized and a yield of 74% is obtained. The overall yield of the process, comprising all steps, is 69%. The purification steps are monitored using SDS-PAGE and the purity of recovered C-PC is confirmed by absorption and emission spectroscopy and RP-HPLC. Results show that EBAC method is a scalable technology that allows large quantities of C-PC to be obtained without product loss, maintaining a high protein recovery while reducing both processing cost and time.


Serum levels of soluble interleukin-2 receptor in patients with ANCA-associated vasculitis.
Serum soluble interleukin-2 receptor (sIL-2R) concentrations were determined using the ELISA method in 19 cases of ANCA-associated vasculitis. These patients were classified as 7 cases of Wegener's granulomatosis (WG) and 12 cases of microscopic polyangiitis (MPA). Elevated levels of sIL-2R were present in the sera of these patients. Levels of serum sIL-2R were not significantly different in patients with WG and MPA either in the active or inactive phase, so the results were expressed as a unified ANCA associated vasculitis group. Concentrations of serum sIL-2R were significantly higher in ANCA-associated vasculitis during the active phase than during the inactive phase (p<0.05), and serum sIL-2R levels were significantly increased in these patients, in the active or inactive stage, compared with a group of healthy subjects (p<0.05). In patients with vasculitis, serum sIL-2R levels correlated with serum levels of C-reactive protein (p<0.05). In the active phase, concentrations of serum sIL-2R correlated to creatinine concentrations. No correlation was found between sIL-2R and ANCA levels in any of the stages of the disease. These findings suggest cellular immune activation in ANCA associated vasculitis.


Ser-262 in human recombinant tau protein is a markedly more favorable site for phosphorylation by CaMKII than PKA or PhK.
Several kinases have been shown to phosphorylate tau protein at Ser-262, an important site involved in the regulation of the binding of tau to microtubules. In this study we compared the phosphorylation of tau at Ser-262 by CaMKII, PhK and PKA in vitro as determined by radioimmunoblots developed by the monoclonal antibody 12E8 which recognizes P-Ser-262 and P-Ser-356; and Ab-262, a polyclonal antibody which is specific to unphosphorylated Ser-262 in tau. We found that the phosphorylation at Ser-262 was several times more effective by CaMKII than PKA or PhK. Employing rat brain extract as a source of all brain kinases and KN-62, a specific inhibitor of CaMKII, we found that CaMKII accounts for approximately 45% of phosphorylation at Ser-262. Furthermore, in rat brain slices kept metabolically active in oxygenated artificial CSF, phosphorylation of tau at Ser-262 was (i) increased up to 120% in the presence of bradykinin, a CaMKII activator, and (ii) inhibited by approximately 35% in the presence of KN-62. Thus, CaMKII is a major tau Ser-262 kinase in mammalian brain.


Miniature varifocal objective lens for endomicroscopy.
A miniature catadioptric lens for endoscopic imaging based on the principle of wavelength division multiplexing is presented. We demonstrate change of the magnification and the field of view (FOV) of the lens without any mechanical adjustment of the optical elements. The lens provides magnifications of ~-1.5× at 406-750 nm and ~-0.2× at 800 nm. The lens is used to demonstrate large-FOV (1.3 mm) reflectance imaging and high-resolution (0.57 μm) multiphoton fluorescence imaging of unstained mouse tissues.


[Experimental tests and clinical trials of the biologically active food additive Fibromed].
A biologically active food additive--Fibromed--has been tested experimentally and clinically. The additive made from wheat bran by the Reacon Company contains no less than 40% of dietary fibre (cellulose, hemicellulose and lignin). Its effect on multi-organ carcinogenesis induced by N-methyl-N-nitrosourea (MNU) and lipid metabolism was tested in rats. Tumors were induced by combined intramammary injections and intrarectal infusions of the agent. Fibromed was fed (20% by weight) during post-initiation period. It effectively inhibited the development of mammary and colonic tumors and reduced serum-blood cholesterol, triglycerides and beta-lipoproteids. The influence of Fibromed treatment on stool during early post-operative period was studied in surgical cases of colorectal cancer. When administered in a dose of 60 g, daily, starting from days 4-5, Fibromed restored intestinal function 36 hr earlier than in controls. Fibromed should be recommended for prevention of breast and colonic tumors, lipid metabolism disorders and rehabilitation of patients who underwent surgery for colorectal cancer.


Formulary status of drugs in Ontario after Health Canada has issued a serious safety warning: a cohort study.
Drugs are approved for formulary listing based on limited knowledge of their safety. Serious safety issues are often identified after a drug is marketed. To determine whether the listing status of drugs on the Ontario Drug Benefit (ODB) Formulary changes following the identification of safety concerns by Health Canada and whether the results of reviews by people responsible for the ODB Formulary are made public. All new active substances (NAS) approved by Health Canada from January 1, 2002 to March 31, 2012 that subsequently had a warning issued about a serious safety concern were identified. Editions of the ODB Formulary were searched to find which of these drugs were listed on the Formulary before the safety warning was issued. A total of 263 NAS were approved of which 42 subsequently acquired one or more serious safety warnings and 15 of these were listed on the ODB Formulary before the safety warning was issued. The listing status of 14 of the 15 drugs was unchanged after the release of the safety warning. No information is available about whether the listing status of these 14 drugs was reassessed. The ODB Formulary should develop a set of criteria to determine whether the listing status of drugs should be reviewed after Health Canada issues a serious safety warning. The results of any reconsiderations should made public so that prescribers and patients alike know that the ODB Formulary officials still regard the drugs as having a positive benefit to harm ratio.


Safety and efficacy in geese of a PER.C6-based inactivated West Nile virus vaccine.
Studies were performed with an inactivated vaccine against the mosquito-borne flavivirus, West Nile virus (WNV). The mammalian cell line, PER.C6, was selected as the platform for WNV growth since both the neurovirulent strains NY99 and ISR98 that cause epidemics in humans and high mortality in geese, respectively, could be propagated to high titers (10(9) to 10(10)TCID(50)/ml) on these cells. Based on the high DNA homology of the WNV envelope (E) protein and non-structural protein 5 (NS5), and identical neurovirulence in mice and geese, we concluded that NY99 and ISR98 viruses are closely related and therefore vaccine studies were performed with ISR98 as a model for NY99. A robust challenge model in domestic geese was set up resulting in 100% mortality within 7 days of intracranial challenge with 500 TCID(50) WNV. Geese were used to assess the efficacy and safety of an inactivated WNV vaccine produced on PER.C6 cells. Efficacy studies demonstrated 91.4% (53/58) protection of geese compared to no protection (0/13) in geese receiving a sham vaccine. A follow-up study in 1800 geese showed that the vaccine was safe with a survival rate of 96.6% (95% lower CL 95.7%). Initial studies on the correlates of protection induced by the vaccine indicate an important role for antibodies since geese were protected when injected intra-cranial with a mixture of serum from vaccinated, non-challenged geese and WNV. In all, these results provide a scientific basis for the development of an inactivated WNV vaccine based on NY99 produced on PER.C6 cells for human and equine use.


Double-blind evaluation of etodolac (200 mg, 400 mg) compared with zomepirac (100 mg) and placebo on third molar extraction pain.
This controlled, single dose study has demonstrated that compared with placebo, substantial analgesia is obtained with 200 and 400 mg doses of etodolac. The analgesic effects of both doses of etodolac were not notably different from each other or significantly different from zomepirac, a proven analgesic. With respect to safety, both doses of etodolac were well tolerated, with no reports of serious or dose related adverse side effects.


Transcription factor-induced, phased bending of the E-selectin promoter.
E-selectin is an endothelial adhesion molecule that is critically involved in neutrophil adhesion and recruitment. All DNA elements required for interleukin-1 inducibility have been located in the proximal promoter: an NF-ELAM1/ATF site, two NF-kappa B sites (I and II), the NF-ELAM2 element and a TATA box. We show here that interleukin-1 induced promoter activity is exquisitely sensitive to the spatial arrangements of these elements. Phasing of the ATF and NF-kappa B II elements indicates that their relative helix orientation is more important than distance per se. This sensitivity is partly due to a requirement for correctly oriented, transcription factor-induced DNA-bending. (i) Band shift analyses with permuted ATF- and NF-kappa B elements show that their associated factors all bend DNA. (ii) One can functionally replace the NF-ELAM1/ATF element by a subset of a panel of DNA fragments that contain defined bends in various planes. We conclude that the main role of the factors binding at the NF-ELAM1/ATF element is to alter the conformation of the E-selectin promoter, presumably looping distant enhancer elements into each other's proximity.


Assessment of red mud as sorptive landfill liner for the retention of arsenic (V).
The sorption of AsV on red mud (bauxite residue), produced in the ALCOA-San Cibrao factory (Spain), was assessed in view of its potential use as sorptive liner of landfills for the attenuation of As-rich leachates. The operating parameters evaluated, using batch-type procedures, comprised the effects of time, solution pH, AsV concentration (sorption isotherm) and presence of phosphate on the AsV sorption. The results showed that the red mud efficiently sorbed AsV. The sorption was fast, with a major fraction of initial AsV being removed in a few minutes or hours of contact, depending on AsV concentration. The kinetic process was well described by the pseudo-second order equation, which points to chemisorption is involved, whereas surface (film) diffusion chiefly governs the rate of AsV sorption for the red mud system. Sorption of AsV was strongly pH-dependent. Maximum removal (>98%) was observed at slightly acidic pH (pHmax = 5.5-6), while AsV sorption considerably decreased at both highly acidic and alkaline pH. The percentages of sorbed AsV decreased with the increasing solution AsV concentration, and the AsV sorption capacity (up to 43.5 mmol/kg) of the red mud was higher (∼4 -fold) at pH ∼6 than at pH ∼9.2 (natural pH of the red mud). The presence of P at equimolar or 1:10 As/P molar ratios reduced AsV sorption by ∼20% and 30%, respectively. Simulations of AsV migration taking into account the effects of dispersion and diffusion through an hypothetical red mud liner, using the sorption parameters and the geotechnical-hydraulic conductivity characteristics of the RM, predicted a deeper migration of AsV in the liner at pH∼9.2 than at pH∼6 and a minimum thickness of ∼90 cm and ∼20 cm, respectively, for a RM liner to decrease the solution AsV concentration from highly toxic 1 mM to a safe <0.133 μM (<10 μg/L) level, after a 35-years period.


Phosphatidylcholine bilayers. A theoretical model which describes the main and the lower transitions.
We present a theoretical model which describes both the main and the lower phase transition in phosphatidylcholine bilayers. The main transition involves a melting of the hydrocarbon chains while the lower transition is seen as a nematic to isotropic transition involving entire lipid molecules (which are rod shaped when projected onto the bilayer plane). This latter transition is consistent with experimental data which suggest the presence of long-axis rotation for temperatures below the main melting transition. The model is extended to mixtures of phosphatidylcholines and compared with experimental data.


[Embolization of the hypogastric artery in postpartum haemorrhage. Case report].
Selective embolization of the hypogastric artery is nowadays commonly used for the haemostasis of gynaecological cancer patients. Also re-embolization is possible in the cases of repeated bleedings. We present this method based on the summary of three obstetrical patients in our hospital. In these patients, primary management failed to control bleeding after parturition caused by anatomic reasons which made it difficult to access the bleeding and to achieve haemostasis. During intervention we catheterized the visceral branch of the internal iliac artery selectively via an access in the common femoral artery. Thereafter we blocked the artery with Spongostan fillings. We had one patient, where we applied embolization in retroperitoneal haemorrhage after Caesarean section and supravaginal amputation of the uterus. In two other cases we successfully managed vaginal haematoma by embolization, whereas multiple surgical treatments were unsuccessful. The advantage of this method is that it does not require laparotomy or vaginal exploration. The disadvantage is that a well-equipped laboratory of angiography and an interventional radiologist are also required. Orv Hetil. 2018; 159(39): 1602-1606.


[Baicalin increases the antioxidant capacity via promoting the nuclear translocation of NF-E2-related factor 2 (Nrf2) in N2a/APPswe cells].
To investigate the protective effect and related mechanism of baicalin in murine neuroblastoma N2a cells stably expressing human Swedish mutant amyloid precursor protein (APP) (N2a/APPswe cells), a cellular model of Alzheimer' s disease (AD). MTT assay was performed to observe the effect of baicalin (0.1, 0.5, 1, 5, 10, 20) μmol/L on the viability of N2a/APPswe cells. After N2a/APPswe cells were incubated with (1, 5, 10) μmol/L baicalin for 48 hours, xanthine oxidase assay was used to test superoxide dismutase (SOD) activity and thiobarbituric acid method to detect malondialdehyde (MDA) content in each group. Real-time quantitative PCR was applied to determine nuclear factor erythroid 2-related factor 2 (Nrf2) mRNA, and Western blotting to examine protein levels of total Nrf2, nuclear Nrf2 and nuclear factor κB (NF-κB) in N2a/APPswe cells exposed to different doses of baicalin. Immunofluorescence staining was also used to observe the distribution of Nrf2. We found that baicalin pretreatment increased cell viability. Compared with the control group (N2a/wt cells), SOD activity in N2a/APPswe cells significantly decreased, and MDA content significantly increased; but SOD activity was improved and MDA production was inhibited after pretreatment with baicalin, especially with 10 μmol/L bacalin. Both mRNA and total protein expression of Nrf2 were not significantly changed in baicalin treatment group compared with N2a/APPswe group, but the nuclear protein of Nrf2 distinctly increased after treatment with baicalin. In addition, baicalin decreased the level of nuclear NF-κB protein. Furthermore, immunofluorescence staining revealed that baicalin promoted the translocation of Nrf2 to the nucleus. Baicalin has the protection against oxidative stress via activation of Nrf2 in N2a/APPswe cells.


Alcohol-related traffic accidents with fatal outcomes in the city of Sao Paulo.
The aims of the present study were to characterize fatal traffic accident victims in a major urban center in Brazil and their association with alcohol consumption. Cross-sectional study of 907 fatal traffic accident victims in Sao Paulo, in 2005. Adult males between the ages of 25 and 54 represented the majority of cases with positive blood alcohol concentrations (BAC). Overall, males had a higher proportion of BAC and mean BAC than females. Pedestrians, particularly those with no detectable BAC, were typically older than other victims. Most accidents (total and BAC-positive) happened on weekends between midnight and 6 a.m. Considering all victims, 39.4% were positive (BAC over 0.1g/l). When only drivers (automobile, motorcycle and bicycle) were evaluated, 42.3% had BAC over the legal limit (0.6g/l). Alcohol is associated with nearly half of all traffic accident deaths in the city of Sao Paulo, especially for days and times associated with parties and bars (weekends between 12 a.m. and 6 a.m.).


[Conflicts of interest in clinical practice. Ethical analysis of some relationships with the pharmaceutical industry].
Sometimes, the prescription practice of physicians can be influenced by factors that are not related to scientific evidence due to the appearance of several conflicts of interest. These conflicts cause social concern and have prompted actions to regulate the ethics of individual and corporative activities related to healthcare. We analyzed the ethical problems involved in the physician-industry relationship. For this purpose, we considered as the main actors related to this problem, the pharmaceutical industry and their marketing strategies, medical doctors and the independence and objectivity that should guide prescriptions and, finally, patients and their right to receive prescriptions based on scientific evidence. From the point of view of the Bioethics principles, Beneficence would not be respected when gifts or other donations received from the industry affect doctor's independence. Non Maleficence principle could be jeopardized if there is an increased risk of treatment failure and finally Justice could be altered if there is a cost increase for either patients or health institutions. As a conclusion, we consider that the presence of conflicts of interest in the relationship of physicians with the pharmaceutical industry is an important ethical problem. In consequence, this group endorses the recommendations of the Chilean Association of Medical Scientific Societies and advices to include ethical guidelines on this topic in the curriculum of medical schools.


Interleukin-17 regulates chemokine and gelatinase B expression in fibroblasts to recruit both neutrophils and monocytes.
Interleukin 17 (IL-17) is a proinflammatory cytokine, produced only by activated lymphocytes, but with a broad cellular host range. The effects of IL-17 on fibroblasts were investigated by analysis of the induction of chemokine and matrix metalloprotease (MMP) mRNA levels by RT-PCR. IL-17 stimulated CC chemokine (monocyte chemotactic protein-1; MCP-1/JE) and CXC (KC, MIP-2) chemokine and TIMP-1 mRNA expression in fibroblastoid L929 cells. In normal mouse embryonic fibroblasts (MEF) this induction profile by IL-17 was extended with the mRNAs encoding the chemokine granulocyte chemotactic protein-2 (GCP-2) and the proteases MMP-3, MMP-9 and MMP-13. The MMP-9 and GCP-2 induction by IL-17 in MEF, and the absence of induction in L929 cells, were corroborated by gelatin zymography and ELISA, respectively. The induction of MCP-1/CCL2 by IL-17 was confirmed in human diploid fibroblasts. We conclude that IL-17 regulates differentially chemokine and MMP expression by normal and transformed fibroblasts and is indirectly capable of attracting both monocytes and neutrophils to the inflammatory focus.


Validity of procedure codes in International Classification of Diseases, 9th revision, clinical modification administrative data.
Administrative hospital discharge data are widely used to assess quality of care in patients undergoing certain procedures. However, little is known about the validity of administrative coding of procedure data. We conducted a detailed chart review to evaluate the accuracy and completeness of information on procedures in administrative data. We randomly selected 1200 hospital separations in the period April 1, 1996, to March 31, 1997, from administrative discharge data of 3 acute adult hospitals in Calgary, Alberta, Canada. Each separation record in administrative data contains up to 10 procedure coding fields. The corresponding medical charts were reviewed for recording presence or absence of procedures. We then determined sensitivity to quantify the accuracy of coding presence of procedures in administrative data when these are present in the chart data (criterion standard). The agreement between the 2 databases varied greatly across 35 procedures studied. The sensitivity ranged from 0% to 94%. Of 6 major procedures studied, validity of coding was generally good, with 5 procedures having coding sensitivity of 69% and over and only 1 (lysis of peritoneal adhesion) with a low sensitivity of 41%. In contrast, many minor procedures had low sensitivities. Of 29 minor procedures studied, sensitivity was lower than 50% for 15 procedures, between 50% and 79% for 10, and 80% and over for 4. Validity of information on procedures in administrative discharge data appears to be related to type of procedures. Major procedures that are usually performed in operating rooms are reasonably well-coded. Meanwhile, minor procedures that are routinely performed on wards or in radiology departments are generally undercoded.


Targeted next generation sequencing approach identifies eighteen new candidate genes in normosmic hypogonadotropic hypogonadism and Kallmann syndrome.
The genetic basis is unknown for ∼60% of normosmic hypogonadotropic hypogonadism (nHH)/Kallmann syndrome (KS). DNAs from (17 male and 31 female) nHH/KS patients were analyzed by targeted next generation sequencing (NGS) of 261 genes involved in hypothalamic, pituitary, and/or olfactory pathways, or suggested by chromosome rearrangements. Selected variants were subjected to Sanger DNA sequencing, the gold standard. The frequency of Sanger-confirmed variants was determined using the ExAC database. Variants were classified as likely pathogenic (frameshift, nonsense, and splice site) or predicted pathogenic (nonsynonymous missense). Two novel FGFR1 mutations were identified, as were 18 new candidate genes including: AMN1, CCKBR, CRY1, CXCR4, FGF13, GAP43, GLI3, JAG1, NOS1, MASTL, NOTCH1, NRP2, PALM2, PDE3A, PLEKHA5, RD3, and TRAPPC9, and TSPAN11. Digenic and trigenic variants were found in 8/48 (16.7%) and 1/48 (2.1%) patients, respectively. NGS with confirmation by Sanger sequencing resulted in the identification of new causative FGFR1 gene mutations and suggested 18 new candidate genes in nHH/KS.


Bariatric Surgery Enhances Splanchnic Vascular Responses in Patients With Type 2 Diabetes.
Bariatric surgery results in notable weight loss and alleviates hyperglycemia in patients with type 2 diabetes (T2D). We aimed to characterize the vascular effects of a mixed meal and infusion of exogenous glucose-dependent insulinotropic polypeptide (GIP) in the splanchnic region in 10 obese patients with T2D before and after bariatric surgery and in 10 lean control subjects. The experiments were carried out on two separate days. Pancreatic and intestinal blood flow (BF) were measured at baseline, 20 min, and 50 min with 15O-water by using positron emission tomography and MRI. Before surgery, pancreatic and intestinal BF responses to a mixed meal did not differ between obese and lean control subjects. Compared with presurgery, the mixed meal induced a greater increase in plasma glucose, insulin, and GIP concentrations after surgery, which was accompanied by a marked augmentation of pancreatic and intestinal BF responses. GIP infusion decreased pancreatic but increased small intestinal BF similarly in all groups both before and after surgery. Taken together, these results demonstrate that bariatric surgery leads to enhanced splanchnic vascular responses as a likely consequence of rapid glucose appearance and GIP hypersecretion.


Reverse Austin osteotomy for correction of acquired static hallux adductus.
Hallux adductus, a horizontal plane deformity, often has an iatrogenic etiology especially as a complication of hallux abducto valgus surgery. A case at Sheridan Park Hospital is described in which the patient developed a steadily worsening static hallux adductus following foot surgery. She underwent further corrective procedures for the hallux adductus 11/2 years later. The authors conclude that if a mild static hallux adductus is observed in conjunction with bunionectomy or other surgery, it should be corrected at that time rather than some years later.


Pretreatment of poultry manure anaerobic-digested effluents by electrolysis, centrifugation and autoclaving process for Chlorella vulgaris growth and pollutants removal.
Different pretreatments (electrolysis, centrifugation and autoclaving) coupled with Chlorella vulgaris biological system was used for the treatment of poultry manure anaerobic-digested effluents. The pretreated effluents were used as the growth medium for algal cultivation. The pollutant removal efficiencies of the combined treatments were determined. Electrochemical pretreatment can efficiently remove the ammonia (NH4+), total phosphorus (TP), total organic carbon (TOC), total carbon (TC), turbidity and bacteria in the digested effluents. About 100.0% NH4+, turbidity and bacteria, 97.6% TP, 81.5% TOC and 96.6% inorganic carbon were removed by 5-h electrochemical treatment. The maximal algal biomass accumulation (0.53 g L(-1)) was obtained from culture in the effluents pretreated with 2-h electrolysis. The pollutants removal amounts by the combination of electrolysis and biological treatment were much higher than the other combinations.


Role of afterload in determining regional right ventricular performance during coronary underperfusion in dogs.
The relationship between coronary perfusion pressure and regional myocardial performance of the right ventricular free wall was studied, in the presence or absence of right ventricular hypertension in 13 open-chest dogs. The right coronary artery was perfused through a shunt from a carotid artery. Regional systolic shortening of the right ventricular free wall was measured by means of a sonomicrometric technique at various levels of coronary perfusion pressure. Regional shortening was insensitive to coronary perfusion pressure or flow when it was above 31 mm Hg or 0.27 ml/min per g. Once coronary perfusion was below this critical level, regional shortening in both base to apex and circumferential orientations decreased linearly, depending on the degree of perfusion pressure. Despite the presence of a monoexponential relationship between coronary perfusion pressure or flow and regional shortening, a direct linear relation between perfusion pressure and flow was consistently noted, with or without pulmonary artery banding, suggesting that there is limited autoregulation of right coronary flow. The critical perfusion pressure for maintaining regional myocardial function of the right ventricle was highly dependent on the level of right ventricular systolic pressure (r = 0.64 - 0.72, P less than 0.05). Thus, right ventricular systolic pressure was one of the important determinants of regional wall motion during coronary underperfusion.


Platelet monoamine oxidase activity and interpersonal violence in male suicide attempters.
Low platelet monoamine oxidase B (MAO-B) activity, proxy of low central serotonergic functions, has been shown to correlate with criminal behavior in adolescents that come from an unfavorable psychosocial environment but not in adolescents from good conditions, indicating a link between environment, MAO-B activity and aggressive behavior. The purpose of this study was to examine the association between MAO-B activity and lifetime interpersonal violence in suicide attempters. The study included a total of 28 suicide attempters (18 men and 10 women). Assessments of childhood exposure to and expressed interpersonal violence during childhood and as an adult were carried out with the Karolinska Interpersonal Violence Scale (KIVS). Platelet MAO-B activity was measured with 2-phenylethylamine (b-PEA) as substrate. Broken down by gender, the correlations between platelet MAO-B activity and both exposure scores to interpersonal violence as a child and expressed lifetime interpersonal violence were significant in male suicide attempters (r = -0.61, p = 0.035; r = -0.84, p = 0.0005), but not in women. Our finding of significant associations between interpersonal violence and low MAO-B activity need to be replicated in other cohorts of suicide attempters.


Subchronic effects of dipyrone on the fish species Rhamdia quelen.
The use of the non-steroidal anti-inflammatory drugs such as dipyrone is so widespread that this drug and its metabolites have been detected in effluents and surface water. This study aimed to evaluate the potential toxic effects of dipyrone on the aquatic environment, using a native fish species, Rhamdia quelen. Fish were exposed to three concentrations of dipyrone, 0.5, 5 and 50 μg/L, in the water for 15 days, and hematological, biochemical, genetic and morphological biomarkers were evaluated. The glutathione S-transferase activity decreased in the highest concentration in relation to the control group. In addition, hematocrit, red blood cells and thrombocyte counts were decreased in all three exposed groups in relation to the control group. The comet assay showed DNA damage at the lowest concentration of dipyrone and significant kidney damage. Those results suggest that a constant exposure of aquatic organisms to dipyrone presents potential toxic effects.


Fasting-induced rise in locomotor activity in rats coincides with increased protein utilization.
The aim of this study was to investigate the possible relation between the modifications in locomotor activity (on running wheel) which occur during prolonged fasting and changes in the utilization of energy reserves. In 18-week-old rats, we found that the rate of body mass loss reflects the changes in nitrogen excretion that occur over three phases of fasting: (I) initially decreasing, (II) maintained at a low level and (III) increasing. Locomotor activity started to increase during phase II without a change in its nycthemeral pattern. By contrast, the 10-fold higher daily locomotor activity that occurred in phase III was marked by a higher proportion of diurnal activity. Using 9-, 18-, and 33-week-old rats, in order to obtain a different timing in the metabolic changes during fasting, we could confirm the coincidence between the later rise in locomotor activity and the occurrence of phase III. Refeeding of rats of either age in phase III rapidly suppressed fasting-induced changes in locomotor activity. These data accord with the idea that behavioral changes reflecting the search for food are triggered by a later and reversible change in the utilization of body protein vs. lipid stores during prolonged fasting.


Sensitized near-infrared lanthanide luminescence from Nd(III)- and Yb(III)-based cyclen-ruthenium coordination conjugates.
The development of novel mixed lanthanide-transition-metal (f-d) based supramolecular self-assemblies made from neodymium- and ytterbium-based tetraamide-functionalized cyclen complexes bearing a single 1,10-phenanthroline moiety coordinating to a RuII(bipy)2 (bipy = bipyridine) unit is described. Excitation of the Ru(II) metal-to-ligand charge-transfer band in water gave rise to long-wavelength sensitized emission from the Yb(III) or Nd(III) centers, observed in the near-infrared.


Reprint of: Hydrogen sulfide in stroke: Protective or deleterious?
Hydrogen sulfide is believed to be a signalling molecule in the central nervous system. It is known to increase rapidly following an ischemic insult in experimental stroke. Is it protective or deleterious? This review surveys the relevant information available in the literature. It appears that there is no definitive answer to this question at present. Current evidence seems to suggest that the presence of H2S in the ischemic brain may either be deleterious or protective depending on its concentration, deleterious when high and protective when low. Therefore, it can be inferred that either an enhancement or a reduction of its concentration may be of potential use in future stroke therapy.


Epidemiological study of Middle East respiratory syndrome coronavirus infection in dromedary camels in Saudi Arabia, April-May 2015.
A cross-sectional study was conducted in five regions in Saudi Arabia to investigate the epidemiology of Middle East respiratory syndrome coronavirus (MERS-CoV) infection in dromedary camels (Camelus dromedarius) during April and May2015. Serum and nasal swab samples were tested for MERS-CoV antibodies andribonucleic acid (RNA) using a recombinant enzyme-linked immunosorbent assay (rELISA) and real-time reverse-transcription polymerase chain reaction (rRT-PCR), respectively. The overall MERS-CoV antibody seroprevalence was 80.5%, whereas the overall viral RNA prevalence was 2.4%. The associations of risk factors with each prevalence were quantified using univariate and multivariate analyses. The multivariate models identified region, age, grazing system, exposure to wild animals and dung removal as factors significantly associated with seroprevalence (p ??0.05). A higher seroprevalence was more likely to occur in camels from the Riyadh, Eastern, Northern and Makkah regions than those from the Jazan region; camels ??4 and 1-3 years of age (marginally significant) than calves < 1 year; and camels raised in zero grazing and semi-open grazing systems than those raised in an open grazing system. However, the presence of wild animals and daily dung removal were negatively associated with seroprevalence. On the other hand, region and sex were significantly associated with MERS-CoV RNA prevalence(p ??0.05). A higher viral RNA prevalence was more likely to occur in camels from the Riyadh region and Eastern region (marginally significant) than in those from the Makkah region, and in male camels than female camels. In conclusion, the risk factors identified in this study can be considered to be predictors of MERS-CoV infection in camels and should be taken into account when developing an efficient and cost-effective control strategy.


Cortisol secretion in response to metabolic and inflammatory challenges in dairy cows.
Cortisol in dairy cows is released in an episodic manner underlying a circadian rhythm. The involvement of cortisol in numerous adaptive processes to cope with adverse conditions such as pain and inflammation is well characterized. Recent studies described contradictory effects of nutrition and metabolism on the secretory pattern of cortisol. However, up to now, the direct effects of single metabolites during various metabolic conditions without the profound endocrine changes around parturition on the glucocorticoid secretion in dairy cows have not been described. The objective of this study was to investigate the effects of long-term (56-h) manipulated metabolic states, that is, manipulated plasma concentrations of glucose and β-hydroxybutyrate (BHBA), on the release of cortisol in midlactation dairy cows. Besides the concentration of cortisol at defined time points, its pulsatile secretory pattern was studied in combination with an acute immune challenge through an intramammary lipopolysaccharide (LPS) challenge. Twenty-five midlactation dairy cows were randomly assigned to 1 of 4 treatments (hyperinsulinemic hypoglycemic clamp [HypoG], hyperinsulinemic–euglycemic clamp [EuG], continuous infusion of BHBA [HyperB], or infusion of saline solution for the control group [Control). Different metabolic states induced by infusion treatments affected the characteristics of cortisol secretion (elevation of baseline [the HypoG and HyperB treatments] and decreased peak length [the HypoG treatment]; P < 0.05), whereas amplitude, peak interval, height, peak area, area under the curve (AUC) above the baseline cortisol concentration (AUCb), and the total AUC (AUCt) were not different between infusion treatments. The induced inflammatory response due to the intramammary LPS challenge at simultaneously maintained infusion treatments diminished the pulsatile nature of cortisol release, whereas AUCb (and AUCt, respectively) was lowest for the HypoG treatment compared with the HyperB and Control treatments (P < 0.05). This study indicates that single metabolites (glucose and BHBA) and their availability or turnover (in case of glucose) have a different impact on the regulation of cortisol secretion resulting in changes of its pulsatile release. Furthermore, cortisol release during intramammary inflammation was found to be greater in the HyperB, EuG, and Control treatments compared with the HypoG treatment (P < 0.05). This finding emphasizes the regulatory role of the current metabolic status on the cortisol release during inflammation.


Lactic acid bacteria and yeasts associated with gowé production from sorghum in Bénin.
To identify the dominant micro-organisms involved in the production of gowé, a fermented beverage, and to select the most appropriate species for starter culture development. Samples of sorghum gowé produced twice at three different production sites were taken at different fermentation times. DNA amplification by internal transcribed spacer-polymerase chain reaction of 288 lactic acid bacteria (LAB) isolates and 16S rRNA gene sequencing of selected strains revealed that the dominant LAB responsible for gowé fermentation were Lactobacillus fermentum, Weissella confusa, Lactobacillus mucosae, Pediococcus acidilactici, Pediococcus pentosaceus and Weissella kimchii. DNA from 200 strains of yeasts was amplified and the D1/D2 domain of the 26S rRNA gene was sequenced for selected isolates, revealing that the yeasts species were Kluyveromyces marxianus, Pichia anomala, Candida krusei and Candida tropicalis. Gowé processing is characterized by a mixed fermentation dominated by Lact. fermentum, W. confusa and Ped. acidilactici for the LAB and by K. marxianus, P. anomala and C. krusei for the yeasts. The diversity of the LAB and yeasts identified offers new opportunities for technology upgrading and products development in gowé production. The identified species can be used as possible starter for a controlled fermentation of gowé.


The effects of site conditions and mitigation practices on success of establishing the valley elderberry longhorn beetle and its host plant, blue elderberry.
This study performed the first systematic evaluation of the success of habitat mitigation at establishing the threatened Valley elderberry longhorn beetle (Desmocerus californicus dimorphus) and its host plant, blue elderberry (Sambucus mexicana). Habitat mitigation performed through enforcement of the U.S. Endangered Species Act represents a tightly controlled form of habitat restoration, facilitating the evaluation of restoration practice. Restoration plantings of blue elderberry have been substantial in our study area, the Central Valley of California. Surveys of 30 mitigation sites and 16 nearby natural sites showed that mitigation sites were a fraction of the size of natural habitat areas (mean = 24%) and contained smaller shrubs. The beetle colonized 53% of mitigation sites and its populations were denser in sites with moderate levels of dead stems on elderberry shrubs, and moderate damage to elderberry stems and bark. This likely indicates that the beetle responds to stressed shrubs, which are likely to contain elevated levels of nitrogen. Beetle density also increased with the size and age of mitigation sites. This indicates a need to make restoration sites as large as possible and to monitor these sites for longer than current guidelines suggest, thereby allowing more time for convergence of natural and mitigation sites. Few factors examined here directly influenced the growth of elderberry shrubs, but elderberry grew more rapidly in sites closer to riparian areas, indicating that such sites should be favored for mitigation sites.


Functional role and mechanism of lncRNA LOC728228 in malignant 16HBE cells transformed by anti-benzopyrene-trans-7,8-dihydrodiol-9,10-epoxide.
Lung cancer is a major health problem, and is considered one of the deadliest cancers in humans. It is refractory to current treatments, and the mechanisms of lung cancer are unknown. Long noncoding RNAs (lncRNAs) are involved in various biological processes and human diseases. However, the exact functional roles and mechanisms of lncRNAs are largely unclear. In this study, we attempted to identify lung-cancer-related lncRNAs. We found changes in lncRNA expression in the anti-benzo(a) pyrene-7,8-diol-9,10-epoxide (anti-BPDE)-transformed human bronchial epithelial cell line (16HBE-T cells) using microarrays and qRT-PCR. Of these lncRNAs, LOC728228 was upregulated relative to its expression in control untransformed16HBE (16HBE-N) cells. LOC728228 knockdown inhibited cell proliferation, caused G0/G1-phase cell-cycle arrest, reduced cellular migration, suppressed colony formation in vitro, and inhibited tumor growth in a nude mouse xenograft model. LOC728228 knockdown also suppressed cyclin D1 expression, and the depletion of cyclin D1 induced G0/G1-phase cell-cycle arrest and inhibited cell proliferation, thus influencing the malignant potential of cancer cells. In summary, our results suggest that lncRNA LOC728228 has an oncogene-like function and plays a vital role in human lung cancer.


Evidence that hepatocyte growth factor abrogates contact inhibition of mitosis in Madin-Darby canine kidney cell monolayers.
It is becoming increasingly apparent that hepatocyte growth factor (HGF) plays an important role in kidney development, regeneration, and transformation to carcinoma. Previous in vitro studies have shown that HGF stimulates cell scattering, but not proliferation, in the renal epithelial cell line Madin-Darby canine kidney (MDCK) when grown on plastic at low density. This communication demonstrates that HGF treatment of confluent monolayers of MDCK also stimulates DNA synthesis and cell division. HGF stimulated thymidine incorporation in confluent MDCK cell monolayers grown on plastic in a dose dependent fashion, but did not stimulate thymidine incorporation in MDCK cells at 10-20% confluency on plastic. Additionally, basolaterally, but not apically, applied HGF stimulated thymidine incorporation in confluent MDCK cell monolayers grown on filters. Immunofluorescent labeling of nuclei in control and HGF treated MDCK cell monolayers grown on filters demonstrated an increase in mitotic figures. Confocal X-Z section views and direct cell counts of MDCK cell monolayers grown on filters demonstrated an increase in cell number after HGF treatment compared to controls. This is the first report of HGF stimulating cell proliferation in previously quiescent renal epithelial cell monolayers. This model will be useful for studying the mechanisms controlling cell proliferation rates in epithelial tissue.