Factors affecting responses on Dermatology Life Quality Index items among vitiligo sufferers.
Finlay and Khan have recently suggested that the Dermatology Life Quality Index (DLQI) can be used to measure the effects of dermatological conditions on the quality of patients' lives. The aims of this study were to assess its applicability in a nonclinic sample of vitiligo sufferers and to measure its relationship with questionnaires designed to measure a variety of psychological and demographic factors. The DLQI was completed by 614 members of the Vitiligo Society in a postal survey. The results supported the validity of the DLQI for this sample. DLQI scores were related to perceived stigma (a version of Ginsburg and Link's psoriasis stigma questionnaire), recent experiences, self-esteem (Rosenberg's scale), personal distress (both a symptom checklist and the 12-item General Health Questionnaire) and race, suggesting that levels of disability might be reduced by interventions that target these variables.


Endothelial nitric oxide synthase in dorsal root ganglia during chronic inflammatory nociception.
Nitric oxide (NO) is a gaseous molecule implicated both in vascular tone and nociceptive transmission. The capillary blood supply to the dorsal root ganglia (DRG) is unique because it is highly permeable to several low and high molecular-weight compounds. This anatomical situation leads to a potential role of endothelial nitric oxide synthase (eNOS) in inflammatory nociception, which is not well established. Therefore, we examined the role of eNOS in DRG in a murine chronic inflammatory pain model induced by complete Freund's adjuvant using L-N(5)-(1-iminoethyl)ornithine (L-NIO), a potent inhibitor of eNOS activity. Pain state was examined using a behavioral test. The expression of eNOS, platelet endothelial cell adhesion molecule-1 (CD31) and vascular endothelial growth factor (VEGF) was examined by immunofluorescence. In control animals, CD31 was detected in vessels; VEGF was localized both in vessels and neurons while a weak eNOS immunopositivity was detected in both vessels and in neurons. Under inflammatory pain conditions, eNOS, CD31 and VEGF immunopositivity increased. Administration of L-NIO significantly attenuated thermal hyperalgesia by 24 h and decreased eNOS activity and CD31 immunopositivity by 7 days. VEGF was unaffected. Our results show that eNOS plays a nociceptive role in the early phases of inflammation while in the later phases it may be involved in neurotrophic support.


Identification of c-Cbl as a new ligase for insulin-like growth factor-I receptor with distinct roles from Mdm2 in receptor ubiquitination and endocytosis.
The insulin-like growth factor receptor (IGF-IR) plays several pivotal roles in cancer. Although most studies on the function of the IGF-IR have been attributed to kinase-dependent signaling, recent findings by our group and others have implicated biological roles mediated by ubiquitination of the receptor. As previously reported, the E3 ligases Mdm2 and Nedd4 mediate IGF-IR ubiquitination. Here we show that c-Cbl is a novel E3 ligase for IGF-IR. On ligand stimulation, both Mdm2 and c-Cbl associate with IGF-IR and mediate receptor polyubiquitination. Whereas Mdm2 catalyzed lysine 63 (K63) chain ubiquitination, c-Cbl modified IGF-IR through K48 chains. Mdm2-mediated ubiquitination occurred when cells were stimulated with a low concentration (5 ng/mL) of IGF-I, whereas c-Cbl required high concentrations (50-100 ng/mL). Mdm2-ubiquitinated IGF-IR was internalized through the clathrin endocytic pathway whereas c-Cbl-ubiquitinated receptors were endocytosed via the caveolin route. Taken together, our results show that c-Cbl constitutes a new ligase responsible for the ubiquitination of IGF-IR and that it complements the action of Mdm2 on ubiquitin lysine residue specificity, responsiveness to IGF-I, and type of endocytic pathway used. The actions and interactions of Mdm2 and c-Cbl in the ubiquitination and endocytosis of IGF-IR may have implications in cancer. In addition, identification and functional characterization of new E3 ligases are important in itself because therapeutic targeting of substrate-specific E3 ligases is likely to represent a critical strategy in future cancer treatment.


Long term follow up of two independent patients with Schinzel-Giedion carrying SETBP1 mutations.
Schinzel-Giedion syndrome (SGS, MIM #269150) is a rare syndrome characterized by severe intellectual disability, typical facial gestalt, hypertrichosis and multiple congenital malformations including skeletal, genitourinary, renal and cardiac abnormalities. The prognosis of SGS is very severe and death occurs generally within a few years after birth. In 2002, we reported 2 children with SGS with a follow-up of 3 years. They presented a very similar and particular phenotype associating distinctive facial gestalt, severe developmental delay, megacalycosis, progressive neurodegeneration, alacrimi, corneal hypoesthesia and deafness. Furthermore, temporal bone imaging revealed a tuning-fork malformation of the stapes. In 2010, Hoischen et al. identified in SGS patients pathogenic heterozygous de novo mutations in SETBP1. We sequenced SETBP1 in our patients and found the previously reported c.2608G>A (p.Gly870Ser) mutation in both children. Since 2002, one of our patients died at 6 years old and the other patient is still alive at 15 years old. Such a life expectancy has never been reported so far. We describe herein the follow up of the 2 children during 6 and 15 years respectively. This article gives further evidence of the implication of SETBP1 as the major gene of SGS, and reports the previously unseen natural evolution of the disease in a 15 years old patient.


Estimation of the ischemic penumbra based on CT perfusion a pilot study.
Ischemic penumbra (IP), the target of thrombolytic therapies, could be estimated by the mismatch region between magnetic resonance imaging (MRI) diffusion- and perfusion-defined abnormalities; however, the accuracy of this method has been challenged recently. In this study, we try to establish a method for calculating IP size based on computed tomography perfusion (CTP) and to observe the early evolution of IP in detail. The middle cerebral artery occlusion (MCAO) model in monkey was used to compare the accuracy in estimating the IP between CTP and MRI methods. A receiver operating characteristic (ROC) curve was performed to calculate the IP threshold of the different CTP parameters, and then the best parameter was obtained. The dynamic evolutions of estimated size of IP by these two methods were compared. Among the three CTP parameters, relative cerebral blood flow (rCBF) had the highest sensitivity (83.3%) and specificity (98.5%) in estimating the IP. The optimal cutoff threshold of rCBF was 0.203. During the first 15 hours of the MCAO model, the estimated size of IP by the rCBF was larger than that of the MRI method; however, this relationship was reversed 15 hours later. This study suggests that the rCBF method is more accurate in estimating the IP since previous studies have reported that the MRI method underestimated the exact IP in the early stage of ischemia and overestimated the exact IP in the later stages. Further experimental and clinical studies are needed to validate the conclusion.


Structure Evolution and Spin-Glass Transition of Layered Compounds ALiFeSe2 (A = Na, K, Rb).
Three new layered compounds, namely NaLiFeSe2, KLiFeSe2, and RbLiFeSe2, have been discovered. NaLiFeSe2 adopts a trigonal CaAl2Si2-type structure with space group P3̅m1, while the other two possess a tetragonal ThCr2Si2-type structure with space group I4/mmm. Structural refinements reveal that Li and Fe atoms randomly occupy the same sites in all these compounds without ordering. It is found that the radius of the alkali metals plays a vital role in determining the symmetry of this series of compounds. The substitution of Li at the Fe site shortens the layer spacing and elongates the A-Se bond length in the ThCr2Si2-type structure. The elongated Na-Se bond length would destabilize the ThCr2Si2-type structure in NaLiFeSe2, suggesting that NaxFe2-ySe2 lies at the border of ThCr2Si2-type and CaAl2Si2-type structures. Magnetic and resistivity measurements demonstrate that these compounds exhibit anisotropic spin-glass and narrow-band-gap semiconducting characteristics. First-principles calculations indicate that the introduction of Li enhances strong localization and weakens the correlation of the 3d electrons of Fe, which are responsible for the observed spin-glass transition and semiconducting conductions.


[Vasopressin in tissue basophils of the dura mater of white rats].
By an indirect immunohistochemical method with fluorescein-isothiocyanate (FITC) and horse radish peroxidase as markers (HRP) the presence of vasopressin was shown in cells of dura mater in white rats. Mast cells were identified after staining with methylene blue by the metachromatic granularity of the cytoplasm. It was shown that the number of cells found by means of FITC luminescence corresponds with their number found by means of methylene blue. The use of conjugate with HRP unveils a lesser number of vasopressin-containing cells.


Nutrition status, bone mass density, and selective serotonin reuptake inhibitors.
The association between selective serotonin reuptake inhibitor (SSRI) use and bone mass density (BMD) has been debated. Inadequate diet, which may occur in depressed individuals prescribed SSRIs is also associated with decreased BMD. This study seeks to determine if SSRI use in adults is associated with lower than average BMD while controlling for nutrition related variables. Further, it investigates whether there are potential interactions between micronutrients and SSRI use on BMD. Adults, 655 with an SSRI prescription ≥180 days and 12,372 non-users, were identified in the 2005-2014 National Health and Nutrition Examination Survey (NHANES) data. Survey respondents were propensity score matched on propensity to have an SSRI prescription and compared on femoral neck BMD t-scores. A sub-analysis within SSRI users was conducted to calculate the odds ratio (OR) of having a low (osteopenia or osteoporosis) BMD t-score given SSRI exposure and inadequate daily micronutrient intake. Inadequate daily micronutrient intake was common; over half of SSRI users and non-users had inadequate calcium, vitamin D, and potassium. SSRI use was associated with an absolute reduction of 0.11 in BMD t-score. Inadequate daily vitamin D intake was associated with lower BMD t-scores in both SSRI users and non-users. The interaction of SSRI use and inadequate daily intake of zinc was also associated with low BMD (OR: 1.11, 95% CI: 1.01-1.23). Patient health may be improved by nutritional education, referral to a dietitian, or by micronutrient monitoring by the prescribing physician.


[Axial computer tomography of the neurocranium (author's transl)].
Computer tomography (CT), a new radiographic examination technique, is very highly efficient, for it has high informative content with little stress for the patient. In contrast to the conventional X-ray technology, CT succeeds, by direct presentation of the structure of the soft parts, in obtaining information which comes close to that of macroscopic neuropathology. The capacity and limitations of the method at the present stage of development are reported. Computer tomography cannot displace conventional neuroradiological methods of investigation, although it is rightly presented as a screening method and helps towards selective use. Indications, technical integration and handling of CT are prerequisites for the exhaustive benefit of the excellent new technique.


Postpartum plasma exchange as adjunctive therapy for severe acute fatty liver of pregnancy.
Acute fatty liver of pregnancy (AFLP) is a rare disease of progressive hepatic insufficiency and secondary systemic compromise that poses significant fetal-maternal risk. Plasma exchange (PEX) is an effective bridge therapy to sustain liver function and enable hepatocellular regeneration to occur in nonpregnant patients following acute decompensation of a chronic liver disease or while awaiting liver transplantation. The application of PEX for patients with AFLP is a novel concept; since 1988 we have utilized postpartum PEX (PPEX) as adjunctive medical therapy for six patients with severe AFLP. Before PPEX initiation, four patients had signs and symptoms of encephalopathy, three required ventilatory support, five had advanced liver insufficiency, and all six were developing renal failure. PPEX was initiated 2-8 days following delivery and repeated (two to four times, mean = 3) at 24-48-h intervals thereafter. All patients responded with composite clinical (symptoms/signs) and laboratory improvement; the average length of hospitalization following final PPEX for five of six patients was 7 days. No significant PPEX-related complications occurred. PPEX utilization in patients with severe AFLP may enhance maternal recovery by preventing secondary sequelae from hepatic insufficiency until spontaneous healing can occur. Further study appears to be indicated to validate a role for PPEX as supportive therapy for puerperal patients with AFLP suffering multiorgan failure.


Prevalence and risk factors associated with hepatitis C in ED patients.
The objective of this study was to measure the prevalence of and identify risk factors associated with hepatitis C virus (HCV) in emergency department (ED) patients. Adults presenting to an urban university teaching hospital, having blood drawn as part of their routine evaluation, had an extra tube drawn and tested for HCV. English-speaking adults consenting to participate in the survey portion of the study were administered an in-depth risk factor questionnaire. A case-control analysis was used to identify risk factors in HCV+ compared with HCV- subjects. Contingency table analyses using the Fisher exact test, odds ratios (OR), and 95% confidence intervals (CI) were used for risk factor identification. Of 223 blood samples, 38 (17%) were positive for antibodies for HCV. One hundred twenty-one subjects (54%) agreed to the risk factor survey, 18 (15%) of whom were HCV+. Of the 18 HCV+ survey participants, 12 new diagnoses of HCV were made. A history of injection drug use was the most significant risk factor associated with HCV (OR 858.5, CI 61.8-22,026.5). A high prevalence of HCV is found in selected urban ED patients. Most of these patients have a constellation of risk factors including a history of injection drug use. Efforts to identify at risk patients for serologic testing and follow-up should be initiated. Identifying undiagnosed HCV can lead to interventions to decrease transmission as well as reduce the morbidity and mortality of disease.


Superoxide dismutase (glu100-->gly) in a family with inherited motor neuron disease: detection of mutant superoxide dismutase activity and the presence of heterodimers.
Superoxide dismutase glu100-->gly, a mutation known to be associated with familial motor neuron disease (familial amyotrophic lateral sclerosis) has been detected in one symptomatic and five of seven asymptomatic members of a family with a history of this disease. On average, the individuals with the mutation had 75% of normal red blood cell superoxide dismutase activity. Native polyacrylamide gels stained for superoxide dismutase activity showed two abnormal bands in the family members identified as carrying the mutation. This indicates that active mutant enzyme is present in red cells and forms stable homodimers and heterodimers with the normal chain. A silent mutation in exon 4, not associated with motor neuron disease, was also detected in one family member.


Evaluation of socio-economic factors causing discontinuation of epilepsy treatment resulting in seizure recurrence: a study in an urban epilepsy clinic in India.
The prevalence rate of epilepsy in India ranges between 4.15 and 7.03 per 1000 population. In the developing countries, the major problems of epilepsy are lying in the treatment gap and discontinuation of treatment due to various adverse socio-economic factors. The objective of this study was to evaluate the rate of discontinuation of epilepsy treatment and its related socio-economic factors responsible for discontinuation. Among 1450 patients with epilepsy who were recurrently followed up at an intervals of 2 months from 05 January to 06 January; 620 patients discontinued their treatment. Among them 88.7% patient had breakthrough seizures for more than in two occasions. Socio-economic factors in respect to the treatment were evaluated during the follow-up period vis-a-vis income and expenditure, unemployment status, negative attitude towards medical treatment, non-availability of drugs locally, co-morbid psychiatric and other illnesses, polytherapy and socialillusional thoughts about epilepsy. Discontinuation of epilepsy treatment was detected in 42.75% (n = 620) of total patients resulting in recurrence of seizures. Reasons for discontinuation were multiple in most of the cases. The discontinued group had an average annual cost of treatment and income of Rs. 5500 ($110) and Rs. 12,800 ($256), respectively, amounting to 40% of their total income being expended for the cost of the treatment, while in continued group annual cost of treatment and income were Rs. 4500 ($ = 90) and Rs. 24,400 ($ = 580) respectively amounting to only 18% of the total income (p < 0.001) for the cost of treatment. Among the discontinued group, 90% of the patients reported the cost factors, 29.09% due to the unemployment, 20% from the frustration and despair, 20.09% due to non-availability of medicines locally, 17.27% spiritual illusional thoughts about epilepsy, 10% for marital disharmony were the causes for discontinuation of treatment. In the discontinued group, 10% got polytherapy against 9.03% in the continued group (p > 0.01), co-morbid psychiatric illnesses were observed in 4.54% against 3.25% in the continued group (p > 0.10). The study showed a significant number of patients (42.75%) discontinued epilepsy treatment within 1 year due to poor knowledge regarding the problem of discontinuation, cost and income disparity, unemployment, spiritual illusional thoughts about epilepsy, frustration and mental impairment, lack of uniform availability of drugs in local market. To tide these shortcomings, uniform availability of cheaper antiepileptic drugs with adequate information and communication regarding the disease and upliftment of socio-economic status are to be ensured.


Inhibitory effects of medicinal mushrooms on α-amylase and α-glucosidase - enzymes related to hyperglycemia.
In Asia, medicinal mushrooms have been popularly used as folk medicine and functional foods. In this study, our aim was to examine the inhibitory effects of six medicinal mushrooms on key enzymes (α-amylase and α-glucosidase) related to hyperglycemia; chemical profiles of bioactive extracts were also examined. The results showed that the n-hexane extract of Coriolus versicolor had the strongest anti-α-amylase activity, while the n-hexane extract of Grifola frondosa showed the most potent anti-α-glucosidase activity. Compared with acarbose, the anti-α-amylase activity of all mushroom extracts was weaker, however a stronger anti-α-glucosidase activity was noted. GC-MS analysis showed that the magnitude of potency of inhibiting α-glucosidase activity varied with the levels of oleic acid and linoleic acid present in the extracts. These findings were consistent with the IC50 values of these free fatty acids on inhibiting α-glucosidase activity. Taken together, this study suggests that oleic acid and linoleic acid could have contributed to the potent anti-α-glucosidase activity of selected medicinal mushrooms.


Preference for full-fat over low-fat foods among individuals suffering from coronary heart disease and healthy controls.
Dietary behaviour can modify the risks for coronary heart disease (CHD). Dietary fat contributes to the sensory characteristics of many foods, but there are individual differences in liking for regular and reduced fat products. Preference for dietary fat might differ between healthy individuals and those of diagnosed CHD status. Preference for full-fat versus low-fat foods was assessed in a group suffering from CHD (N=24) and a healthy control group (N=41). Preferences were evaluated using a series of paired preference tests including 34 food pairs. Further, patterns across fat preference and a range of known risk factors for CHD were examined. The study was conducted in Sweden; March 2004 until May 2006. Overall the full-fat food items were preferred to the low-fat alternatives by both patients and control participants. The pattern of preference responses diverged significantly between patients and controls on only four of the 34 food items, in both directions, why preference related to total fat content per se is not confirmed as differentiating significantly between a group diagnosed with CHD compared to a healthy control group.


Surgeon-performed point-of-care ultrasound for acute cholecystitis: indications and limitations: a European Society for Trauma and Emergency Surgery (ESTES) consensus statement.
Acute cholecystitis (AC), frequently responsible for presentation to the emergency department, requires expedient diagnosis and definitive treatment by a general surgeon. Ultrasonography, usually performed by radiology technicians and reported by radiologists, is the first-line imaging study for the assessment of AC. Targeted point-of-care ultrasound (POCUS), particularly in the hands of the treating surgeon, may represent an evolution in surgical decision-making and may expedite care, reducing morbidity and cost. This consensus guideline was written under the auspices of the European Society of Trauma and Emergency Surgery (ESTES) by the POCUS working group. A systematic literature search identified relevant papers on the diagnosis and treatment of AC. Literature was critically-appraised according to the GRADE evidence-based guideline development method. Following a consensus conference at the European Congress of Trauma & Emergency Surgery (Valencia, Spain, May 2018), final recommendations were approved by the working group, using a modified e-Delphi process, and taking into account the level of evidence of the conclusion. We strongly recommend the use of ultrasound as the first-line imaging investigation for the diagnosis of AC; specifically, we recommend that POCUS may be adopted as the primary imaging adjunct to surgeon-performed assessment of the patient with suspected AC. In line with the Tokyo guidelines, we strongly recommend Murphy's sign, in conjunction with the presence of gallstones and/or wall thickening as diagnostic of AC in the correct clinical context. We conditionally recommend US as a preoperative predictor of difficulty of cholecystectomy. There is insufficient evidence to recommend contrast-enhanced ultrasound or Doppler ultrasonography in the diagnosis of AC. We conditionally recommend the use of ultrasound to guide percutaneous cholecystostomy placement by appropriately-trained practitioners. Surgeons have recently embraced POCUS to expedite diagnosis of AC and provide rapid decision-making and early treatment, streamlining the patient pathway and thereby reducing costs and morbidity.


Epidemiology of vancomycin-induced neutropenia in patients receiving home intravenous infusion therapy.
Vancomycin is frequently used to manage serious resistant gram-positive infections. Neutropenia, whose epidemiology has not been well characterized, is a potentially serious adverse event associated with the use of vancomycin. To characterize the incidence and risk factors for development of vancomycin-induced neutropenia in patients treated with home intravenous vancomycin therapy. A retrospective chart review was conducted of adult patients receiving vancomycin therapy through the University of New Mexico Home Intravenous Infusion Clinic between January 1998 and December 2004. Data collection included demographics, comorbid conditions, dose and duration of vancomycin therapy, indications for vancomycin use, vancomycin concentrations, all concurrent medications, laboratory data, culture and susceptibility data, reasons for antibiotic alteration or discontinuations, all other recorded adverse events, management of adverse events, and outcomes of adverse events. A total of 372 charts of patients managed through the clinic were reviewed and 114 patients treated with vancomycin were identified. Fourteen (12%) cases of vancomycin-induced neutropenia were identified; 4 (3.5%) cases included a reduction in absolute neutrophil count to 500 cells/mm3 or less. The mean +/- SD duration of vancomycin therapy and time to neutropenia were 32 +/- 29 and 26 +/- 15 days, respectively. Laboratory monitoring was performed on a weekly basis and resolution of vancomycin-induced neutropenia occurred promptly after discontinuation. Total vancomycin doses used and serum concentrations were not associated with the development of neutropenia. Vancomycin-induced neutropenia may occur at a higher frequency than previously reported. Clinicians should monitor hematologic parameters at least weekly in patients receiving home intravenous vancomycin therapy.


Molecular resolution to a morphological controversy: The case of North American fossil muskoxen Bootherium and Symbos.
The musk ox (Ovibos moschatus) is the only surviving member of a group of Pleistocene North American musk ox genera (Praeovibos, Ovibos, Bootherium, Euceratherium, and Soergelia) whose taxonomy is uncertain. The helmeted musk ox (Bootherium bombifrons) and the woodland musk ox (Symbos cavifrons) have been synonymised as male and female forms of a single Nearctic species found from Alaska, in the north, to Texas, in the south. However, this reclassification has not been tested using molecular data, despite the potential to use ancient DNA to examine these late Pleistocene taxa. In the present study, we sequenced mitochondrial genomes from seven subfossil musk ox specimens (originally identified as Bootherium and/or Symbos), allowing us to evaluate the identity of these muskoxen, explore their phylogeography, and estimate the timeline for their evolution. We also used nuclear genomic data to determine the sex of six of our seven samples. Ultimately, our molecular data support the synonymisation of the North American muskoxen Bootherium and Symbos.


SMARCA5 methylation and expression in gastric cancer.
Here, we first evaluated SMARCA5 expression and promoter DNA methylation in gastric carcinogenesis. Immunohistochemistry and methylation-specific PCR were analyzed in 19 and 48 normal mucosa and in 52 and 92 gastric cancer samples, respectively. We observed higher immunoreactivity of SMARCA5 in gastric cancer samples than in normal mucosa. Moreover, SMARCA5 promoter methylation was associated with the absence of protein expression. Our findings suggest that SMARCA5 has a potential role in proliferation and malignancy in gastric carcinogenesis.


An autopsy case of mitochondrial encephalomyopathy with prominent degeneration in olivo-ponto-cerebellar system.
We describe a sporadic case of adult-onset, complex I deficiency mitochondrial encephalomyopathy (MEM), the clinical and pathological features of which failed to fit any of the known subgroups of MEM, such as Kearns-Sayre syndrome, mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes or myoclonus epilepsy with ragged-red fibers. Clinically, this patient had only progressive cerebellar ataxia, generalized muscle weakness and hearing loss. The principal finding at autopsy was degeneration of the olivo-ponto-cerebellar system. This case suggests that mitochondrial disease could underlie some cases of olivo-ponto-cerebellar atrophy.


Properties of dairy-manure-derived biochar pertinent to its potential use in remediation.
Conversion of waste products into biochar (BC) is being considered as one of several waste disposal and recycling options. In this study, we produced BC from dairy manures by heating at low temperatures (500 degrees C) and under abundant air condition. The resultant BC was characterized for physical, chemical, and mineralogical properties specifically related to its potential use in remediation. The BC from all manures behaved similarly. Surface area, ash content, and pH of the BC increased as temperature increased, while yield decreased with increasing temperature. The BC was rich in mineral elements such as N, Ca, Mg, and P in addition to C, and concentrations of C and N decreased with increasing temperature as a result of combustion and volatilization; while P, Ca, and Mg increased as temperature increased. For example, C significantly decreased from 36.8% at 100 degrees C to 1.67% at 500 degrees C; whereas P increased from 0.91% to 2.66%. Water soluble P, Ca, and Mg increased when heated to 200 degrees C but decreased at higher temperatures likely due to increased crystallization of Ca-Mg-P, as supported by the formation of whitlockite (Ca,Mg)(3)(PO(4))(2) following 500 degrees C treatment. The presence of whitlockite was evidenced by X-ray diffraction analysis. Quartz and calcite were present in all BC produced. The BC showed appreciable capability of adsorption for Pb and atrazine from aqueous solution, with Pb and atrazine removal by as high as 100% and 77%, respectively. The results indicated that dairy manure can be converted into biochar as an effective adsorbent for application in environmental remediation.


[Three basic kinds of behaviour, a scheme of their neurobiological correlates (author's transl)].
The psychic sphere is to be regarded as the source of meaningful behaviour, which is carried out in the service of the cell community that makes up our body. Three fundamental types of behaviour can be distinguished: the purely practical, the theoretical-practical, and the purely theoretical. These three types of behaviour have three different reasons: the first a determining reason, the second a motivating reason, and the third a supporting reason. The threefold nature of the reasons is related to the threefold needs of the cell community (in this context man is considered as an example of an animal). Possible neurobiological bases of human behaviour are depicted in a schematic figure showing the relation of cerebral centres and sensorimotor functions of the human face including eye movements. The psychic centre may be located in the thalamus, the areas of the central sulcus are regarded as an objectivation zone. This indicates that the motor zones of the cortex, including the frontal adversive fields, are intention zones, and the sensory zones reproduction, expectation, and recollection zones. A system so composed would render possible what we see in every animal being: decision-making, foresight, and learning.


Design and synthesis of aminoester heterodimers containing flavone or chromone moieties as modulators of P-glycoprotein-based multidrug resistance (MDR).
In this study, a new series of heterodimers was synthesized. These derivatives are N,N-bis(alkanol)amine aryl esters or N,N-bis(ethoxyethanol)amine aryl esters carrying a methoxylated aryl residue combined with a flavone or chromone moiety. The new compounds were studied to evaluate their P-gp modulating activity on a multidrug-resistant leukemia cell line. Some of the new compounds show a good MDR reversing activity; interestingly this new series of compounds does not comply with the structure-activity relationships (SAR) outlined by previously synthesized analogs carrying different aromatic moieties. In the case of the compounds described in this paper, activity is linked to different features, in particular the characteristics of the spacer, which seem to be critical for the interaction with the pump. This fact indicates that the presence of a flavone or chromone residue influences the SAR of these series of products, and that flexible molecules can find different productive binding modes with the P-gp recognition site. These results support the synthesis of new compounds that might be useful leads for the development of drugs to control P-gp-dependent MDR.


Zebrafish p53 protein enhances the translation of its own mRNA in response to UV irradiation and CPT treatment.
p53 protein is an important regulatory factor involved in cell growth and development. In our previous study, we demonstrated that recombined zebrafish p53 protein could specifically bind to its own mRNA in vitro. To determine if a similar interaction exists in zebrafish and if this interaction affects zebrafish development, in the present study, we investigated the interaction of p53 protein and its mRNA in zebrafish embryos. Our results revealed that expressed zebrafish p53 protein could bind with its own mRNA in zebrafish embryos. Furthermore, the endogenous activated or ectopically expressed p53 protein could enhance the relative activity of Renilla luciferase fused with p53 3'UTR in response to UV irradiation and CPT treatment, and retarded development of zebrafish embryos was observed.


Hepatic subsegmentectomy with segmental hepatic vein sacrifice.
There is no clinical disorder in partial Budd-Chiari syndrome or in a major hepatic vein ligation in hepatic trauma. When considering these findings, it is significant to investigate hepatic subsegmentectomies in which a major hepatic vein is sacrificed. We performed such hepatic subsegmentectomies in nine cases of hepatocellular carcinoma. With the sacrifice of the right hepatic vein, S7, S8 resection was done in three patients, S7 resection in two patients, S8 resection in one patient, and S5 resection in one patient. With the sacrifice of the middle hepatic vein, S8 resection was done in two patients. These resections were successfully performed with no postoperative problem. Further, there were no significant differences in postoperative liver function tests of the patients from those of a control group of the commonly performed systematic segmentectomy and subsegmentectomy. By performing such resections, resection was made possible in three cases and curative resection was made feasible in six cases.


Determination of free energies of N-capping in alpha-helices by modification of the Lifson-Roig helix-coil therapy to include N- and C-capping.
We have previously shown that varying the N-terminal amino acid in alpha-helical peptides can cause large variations in helix content (Chakrabartty et al., 1993a). The Lifson-Roig theory for the helix-coil transition predicts, however, that substitutions at the N-terminus in an unacetylated peptide should have no effect on alpha-helix stability. We have therefore modified the theory to include these N-capping effects by assigning a statistical weight (the "n-value") to the amino acid immediately preceding a stretch of helical residues. The n-value measures the N-capping propensity of an amino acid, and like the helix propensity (w-value), it is independent of neighboring residues or positions in sequence. The new theory was used, with the experimental data for these substitutions, to calculate n-values and, hence, free energies for N-capping for the amino acids Gln, Ala, Val, Met, Pro, Ile, Leu, Thr, Gly, Ser, and Asn as well as for the acetyl group, which is commonly used to cap peptides. The free energies vary by approximately 1 kcal mol-1 from Gln (worst) to Asn (best), and the acetyl group is nearly as effective as Asn. N-Capping free energies were also found for Leu, Thr, Gly, Ser, and Asn when the N-terminus is charged at pH 5. The unfavorable effect of protonation of the N-terminus in an alpha-helix was found to be approximately 0.5 kcal mol-1. Our results agree well with a survey of N-capping preferences from protein crystal structures and are compared to results from site-directed mutagenesis of N-caps in proteins.


Discovery of novel 5-benzylidenerhodanine and 5-benzylidenethiazolidine-2,4-dione inhibitors of MurD ligase.
We have designed, synthesized, and evaluated 5-benzylidenerhodanine- and 5-benzylidenethiazolidine-2,4-dione-based compounds as inhibitors of bacterial enzyme MurD with E. coli IC(50) in the range 45-206 μM. The high-resolution crystal structure of MurD in complex with (R,Z)-2-(3-[{4-([2,4-dioxothiazolidin-5-ylidene]methyl)phenylamino}methyl)benzamido)pentanedioic acid [(R)-32] revealed details of the binding mode of the inhibitor within the active site and provides a good foundation for structure-based design of a novel generation of MurD inhibitors.


Glucose recovery after intranasal glucagon during hypoglycaemia in man.
We compared the hyperglycaemic effect of intranasal and intramuscular (i.m.) administration of glucagon after insulin-induced hypoglycaemia. Twelve healthy subjects were examined twice, receiving on both occasions an intravenous insulin bolus. Somatostatin and propranolol were administered to block endogenous glucose counterregulation, and glucose turnover was estimated by a 3-[3H]-glucose infusion. When hypoglycaemia was reached, the subjects received either i.m. glucagon of pancreatic extraction (1 mg) or intranasal genetically engineered glucagon (2 mg). The incremental values for plasma glucose concentrations 15 min after intranasal and i.m. administration of glucagon differed marginally. However, after 5 min the glucose appearance rate, as well as the incremental values for plasma glucose, were significantly higher for the i.m. glucagon treatment. The mean time taken for incremental plasma glucose to exceed 3 mmol.l-1 was significantly shorter for i.m. glucagon. The mean plasma glucagon level increased faster after i.m. glucagon than after intranasal glucagon, and the levels remained higher throughout the study period. We conclude that glucose recovery was significantly better after i.m. administration of glucagon than after intranasal administration. However, the differences between the incremental plasma glucose and the time for incremental plasma glucose to exceed 3 mmol.l-1 were not considered of major clinical importance.


Blood-brain barrier permeability after electrically induced seizure in normoglycemic, hypoglycemic, and hyperglycemic rats.
The influence of hyperglycemia and moderate hypoglycemia plus electroconvulsive seizure on the permeability of the blood-brain barrier to protein was studied in rats. Evans blue was used as a blood-brain barrier tracer. Following a single electroconvulsive seizure, slight staining of brain tissue was seen. After 10 electroconvulsive stimuli followed by sustained seizure activity, this phenomenon was more pronounced in moderate hypoglycemic animals. In this group, Evans blue albumin extravasation occurred in all regions of the hemispheres, but the most severe protein leakage was seen in the thalamus, hypothalamus, amygdala nuclei, and frontal, parietal, and occipital cortex. Ten repeated electroconvulsive stimuli applied in case of hyperglycemia made no important difference in blood-brain barrier dysfunction according to normoglycemic group. Our results suggest that moderate hypoglycemia provokes the effect of electroconvulsive seizure on the permeability of the blood-brain barrier.


Comparison of hydrophilic interaction and reversed phase liquid chromatography coupled with tandem mass spectrometry for the determination of eight artificial sweeteners and common steviol glycosides in popular beverages.
Hydrophilic interaction liquid chromatography (HILIC) coupled with tandem mass spectrometry (MS/MS) was used to separate artificial and natural sweeteners approved for use in European Union (EU). Among three tested HILIC columns (BlueOrchid PAL-HILIC, Ascentis Express Si and Acclaim™ Trinity™ P2) the last one was selected for the development of HILIC method due to the best results obtained with it. Early eluting and coeluting compounds in HILIC (acesulfame-K, saccharin, cyclamate, sucralose and aspartame) were successfully separated by the HILIC-based approach for the first time. The developed HILIC method allows for determination of all high potency sweeteners in one analytical run. The calibration curves for all analytes had good linearity within the tested ranges. The limits of detection and quantitation were in the range 0.81-3.30ng/mL and 2.32-9.89ng/mL, respectively. The obtained recoveries used for trueness and precision estimation were from 98.6% to 106.2% with standard deviation less than 4.1%. Sample preparation was reduced to a necessary minimum and contained only proper dilution and centrifugation. More than twenty samples of beverages were analyzed with the developed HILIC method. Finally, the chromatographic parameters of peaks (reduced retention time, width at baseline, width at 50% of peak height, tailing factor and efficiency) obtained in HILIC mode and in RPLC mode were compared. Developed HILIC method along with RPLC method can be applied for rapid evaluation of sweeteners' content, quality and safety control.


Inhibition of human mitochondrial aldehyde dehydrogenase by the disulfiram metabolite S-methyl-N,N-diethylthiocarbamoyl sulfoxide: structural characterization of the enzyme adduct by HPLC-tandem mass spectrometry.
S-Methyl-N,N-diethylthiocarbamoyl sulfoxide (MeDTC-SO) is a known metabolite of the aversion therapy drug disulfiram (DSF). MeDTC-SO is also a potent inhibitor of human mitochondrial aldehyde dehydrogenase (hmALDH) with an IC50 of 1.5 microM. Inhibition of the enzyme by MeDTC-SO resulted in the addition of approximately 100 Da to the molecular mass of the intact protein, as determined by on-line HPLC-electrospray ionization MS (LC-MS). Dialysis of the inhibited protein did not reverse the inhibition, and the molecular mass of 54,533 Da (+/- 0.01%) remained unchanged, indicating that a covalent modification of the protein had occurred. Proteolytic digestion of hmALDH under basic conditions using trypsin at pH 7.8 revealed that the adduct was base labile. However, treating the adducted protein with endopeptidase-Glu-C at pH 3.7 produced a peptide adduct at MH+ = 4924, tentatively attributable to a carbamoylated peptide. This peptide contains three adjacent cysteines, one of which has been implicated as a key amino acid in the highly conserved active site region of ALDH. A pepsin digestion of hmALDH carried out at pH 3.7 and subsequent LC-MS analysis revealed an ion at MH2(2+) = 501.5, corresponding to the carbamoylated peptide FNQGQC1C2C3. This peptide contains the same adjacent active site cysteines. This latter peptide was subjected to LC-MS/MS, which enabled us to determine that the site of carbamoylation was at Cys2. The MS/MS product ion data also confirmed the presence of a carbamoyl group as the adduct species.


Periostin Contributes to Cisplatin Resistance in Human Non-Small Cell Lung Cancer A549 Cells via Activation of Stat3 and Akt and Upregulation of Survivin.
Periostin is upregulated in non-small cell lung cancer (NSCLC). This study was done to explore the function of periostin in the development of cisplatin (CDDP) resistance in NSCLC. The effects of overexpression or knockdown of periostin on CDDP sensitivity was examined in A549 cells. The involvement of signal transducer and activator of transcription 3 (Stat3) and Akt signaling in the action of periostin was checked. The in vivo effect of periostin silencing on CDDP susceptibility was determined in a mouse xenograft model. Periostin was significantly upregulated in CDDP-resistant A549 cells, compared to parental controls. Overexpression of periostin rendered A549 cells more resistant to CDDP-induced apoptosis and enhanced Stat3 and Akt phosphorylation and survivin expression. Periostin-mediated protection against CDDP-induced apoptosis was compromised by downregulation of survivin. Furthermore, knockdown of periostin re-sensitized CDDP-resistant A549 cells to CDDP. After CDDP treatment, greater volume reduction was observed in periostin-silenced xenograft tumors than in control tumors, which was accompanied by reduced levels of phosphorylated Stat3 and survivin in periostin-depleted tumors. In conclusion, periostin promotes CDDP resistance in NSCLC cells largely through activation of Stat3 and Akt and upregulation of survivin and thus represents a promising target for overcoming CDDP resistance.


[Applications of the Fe(3)O(4) nanocomposite modified by Humic Acid in determination of S-phenylmercapturic acid in urine by dispersive solid-phase extraction and HPLC].
Objective: To establish a method for determination the S-phenylmercapturic acid in urine by dispersive solid-phase extraction using Humic Acid/Fe(3)O(4) magnetic nanocomposite as adsorbent. Methods: The 5 ml of urine samples were adjusted to pH 1.0 and extracted by Fe3O4@HA. Then the analytes were separated on EC-C(18) capillary column and detected by HPLC-VWD. The S-phenylmercapturic acid was characterized by the retention time and quantified by peak area and external standard method. Results: The standard curves of SPMA showed significant linearity between 0.04~1.00 mg/L (r=0.999 7) . The average recovery was 94.2%~102.4%. The intra-day and inter-day precisions (RSD) were 2.9~6.7% (n=6) and 3.1~7.5% (n=6) respectively. The detect limit of SPMA was 0.012 g/L (S/N=3) . Conclusion: This method is simple, rapid, sensitive and accurate. It is applicable for determination of SPMA in the urine of works who were exposed to benzene.


[Management of combined psychotherapy and pharmacological treatment. A 'cross sectional' study on a selected sample of psychiatrists].
The association between pharmacological treatment and psychotherapy is frequent. However doesn't exist any agreement or guide-line about the management of this combined therapy. Therefore we considered useful to evaluate which were the most frequent way of management of the combined therapy in a sample of 120 psychiatrists. A 10-items questionnaire finalized to explore the management way of the combined therapy was administered to a sample of 120 psychiatrists. A descriptive analysis of the data was made and the association between different variables was explored. The statistical analysis was performed using SPSS 13.0. 35% of the sample work as a private practitioner, 19.17% is involved in public health (CMHT'S). More than 50% of the sample consider the combined therapy as a effective. In the public field the combined treatment turn out to be the most utilized, opposite than in private practice. 75% of the sample manage alone the combined therapy, while 25% work in team with a colleague. 85% of the pharmacotherapy is utilized in psychosis with positive symptoms, followed by the mood disorder with psychotic symptoms. Neuroleptics are the most frequently prescribed drug. The combined therapy seems to be useful when coherently with the psychotherapy theory model. The pharmacological treatment should be utilized when strictly necessary and, if is possible, the combined therapy should be managed by one psychiatrist.


Current status of branched stent-graft technology in treatment of thoracoabdominal aneurysms.
Endovascular aortic aneurysm repair has been established as an alternative to open surgical reconstruction in appropriately selected patients. Until recently, this approach has been limited to aneurysms not involving critical aortic branches due to the complex nature of designing devices that would preserve important end-organ flow. This article reviews the current status of endovascular approaches to aneurysms involving the thoracoabdominal aorta. The evolution of fenestrated devices and further developments, including reinforced fenestrated branched grafts and directional branches for more complex aneurysms are discussed.


A new strategy toward indole alkaloids involving an intramolecular cycloaddition/rearrangement cascade.
The intramolecular Diels-Alder reaction between an amidofuran moiety tethered onto an indole component was examined as a strategy for the synthesis of Aspidosperma alkaloids. Furanyl carbamate 23 was acylated using the mixed anhydride 26 to provide amidofuran 22 in 68% yield. Further N-acylation of this indole furnished 27 in 88% yield. Cyclization precursors were prepared by removing the carbamate moiety followed by N-alkylation with the appropriate alkyl halides. Large substituent groups on the amido nitrogen atom causes the reactive s-trans conformation of the amidofuran to be more highly populated, thereby facilitating the Diels-Alder cycloaddition. The reaction requires the presence of an electron-withdrawing substituent on the indole nitrogen in order for the cycloaddition to proceed. Treatment of N-allyl-bromoenamide 48 with n-Bu(3)SnH/AIBN preferentially led to the 6-endo trig cyclization product 50, with the best yield (91%) being obtained under high dilution conditions. The initially generated cyclohexenyl radical derived from 48 produces the pentacyclic heterocycle 50 by either a direct 6-endo trig cyclization or, alternatively, by a vinyl radical rearrangement pathway.


A unique pattern of dyskeratosis characterizes epidermolytic hyperkeratosis and epidermolytic palmoplantar keratoderma.
Hereditary skin diseases that are characterized ultrastructurally by intracellular clumpings of keratin tonofilaments, such as Darier disease and Ichthyosis Hystrix of Curth-Macklin, display epidermal dyskeratosis also histologically. Epidermolytic hyperkeratosis (EHK) and epidermolytic palmoplantar keratoderma (Voerner type) (EPPK) are 2 types of autosomal dominant keratodermas, which are also characterized ultrastructurally by intracellular clumpings of tonofilaments but usually without a clear description of histological dyskeratosis. The main aim of the present study was to characterize the histologic signs of keratin aggregation and clumping in the involved epidermis of EHK and EPPK. Two cases of EHK caused by KRT1 mutations and 4 cases of EPPK caused by KRT9 mutations were studied. The biopsies were obtained mostly from the involved skin of the palm. All 6 biopsies were studied histologically, and 4 biopsies (2 EHKs and 2 EPPKs) were also studied ultrastructurally. All 6 cases displayed the characteristic histological epidermolytic changes. In addition, intracytoplasmic and perinuclear eosinophilic homogenizations and round to oval eosinophilic inclusions were identified with varying frequencies in the involved epidermis of all 6 cases. These findings, which were more prominent in the EHK cases, corresponded most likely to the intracytoplasmic aggregates of tonofilaments and to the large round to oval dense clumps of tonofilaments, which were observed ultrastructurally. In conclusion, varying degrees of dyskeratosis are frequently present in EHK and EPPK and should be considered to be a histological characteristic of these disorders.


Value of non-drug treatment and drug treatment in hypertension.
The benefits of the treatment of hypertension currently consist of a substantially reduced incidence of premature stroke, left ventricular failure and malignant hypertension. The benefits for the individual are most clearcut in those who have already had severe or symptomatic hypertension. Older subjects who have a higher risk of stroke and heart failure also show more immediate benefits in terms of stroke and heart failure reduction. However, in the community as a whole, mild hypertensives account for over half the cardiovascular deaths attributable to high blood pressure. In such patients a more systematic approach to the use of non-pharmacological measures for both control of blood pressure and coronary heart disease, coupled where necessary with the judicious use of existing and new antihypertensive and lipid lowering drugs, offers the prospect for a new era of prevention in relation to hypertensive cardiovascular disease.


Kinetic occlusion: further studies of the boundary-flow cue.
Previous work has demonstrated that human beings employ a processing assumption, the boundary-flow constraint, in perceiving the order of depth at an edge. Subjects perceive depth order of surfaces on the basis of the relative motions of an image boundary and a projected surface texture on either side of the boundary. In the present study, adult subjects viewed computer-generated kinematograms in which boundary-flow information provided the only cue for depth order. The results of Experiments 1 and 2 indicate that common motion between boundary and texture and differential motion between boundary and texture can independently generate the perception of ordered depths of surfaces. In Experiment 3, we examined the interaction of two processes involved in the extraction of depth order from boundary-flow displays: (1) the propagation of foreground and background surfaces from texture to boundary; and (2) the computation of depth order of surfaces on either side of the boundary. The results indicate that while the mechanism that computes depth from boundary-flow information functions reliably when the mean distance between texture and boundary is 8.1(0), surface propagation may be disrupted for distances of this magnitude.


Oxidation of N-hydroxyguanidines by copper(II): model systems for elucidating the physiological chemistry of the nitric oxide biosynthetic intermediate N-hydroxyl-L-arginine.
The redox chemistry of models of N-hydroxy-L-arginine, the biosynthetic intermediate in the synthesis of NO by the family of nitric oxide synthase enzymes, has been explored experimentally and theoretically. The oxidation of N-hydroxyguanidine model compounds by Cu(II) was studied as a means of establishing possible metabolic fates and intermediates of this important functional group. These studies indicate than an iminoxyl intermediate is formed and may be an important biological species generated from N-hydroxyguanidines including N-hydroxy-L-arginine.


The Direct Anterior Approach for Hip Revision: Accessing the Entire Femoral Diaphysis Without Endangering the Nerve Supply.
The direct anterior approach (DAA) to the hip has been criticized as an approach that is limited to primary arthroplasty only. Our study objective was to demonstrate, in a cadaveric setting, that an alternate extension of the DAA can be used to reach the femur at the posterior border of the lateral vastus muscle without endangering the nerve supply. The iliotibial tract is split anteriorly and pulled laterally, thereby opening the interval to the lateral-posterior aspect of the vastus muscle. The muscle fascia is incised at the posterior border to access the femoral diaphysis. The vastus mobilization is started distally and laterally to the greater trochanter, leaving a muscular bridge between the vastus and the medial gluteal muscle intact. If it is necessary to open the femoral cavity for implant retrieval, we perform an anterior wall osteotomy instead of an extended trochanteric osteotomy. It was possible to split the iliotibial band and pull it laterally, thereby exposing the entire vastus lateralis muscle. The junction of the vastus lateralis and vastus intermedius was not encountered in all cases, nor was the nerve supply with all nerve fibers in that interval. The alternate technique described here for accessing the femoral diaphysis allows for easy access to the lateral aspect of the vastus lateralis and the femoral diaphysis. Using this technique, it should also be possible to access the femur and perform all necessary reconstructive procedures on it without damaging the surrounding nerve structures.


A convenient enantioselective CBS-reduction of arylketones in flow-microreactor systems.
A convenient, versatile, and green CBS-asymmetric reduction of aryl and heteroaryl ketones has been developed by using the microreactor technology. The study demonstrates that it is possible to handle borane solution safely within microreactors and that the reaction performs well using 2-MeTHF as a greener solvent.


Characterization of polycyclic aromatic hydrocarbons in concurrently monitored surface seawater and sediment along Dalian coast after oil spill.
Polycyclic aromatic hydrocarbons (PAHs) were measured in concurrently sampled surface seawater and sediment collected at 20 sites around Dalian, China 50 days after an oil spill accident. The concentrations of total PAHs ranged from 15 to 160 ng L(-1) in seawater, and from 64 to 2100 ng g(-1) dry weight in surface sediment. The spatial trends of PAHs in seawater, but not in sediment, showed a significant negative correlation with the distance from the oil spill site, indicating a strong source of PAHs from oil spill place to the surrounding seawater. The similar profiles for PAH composition in both crude oil and seawater could indicate that oil spill caused PAHs concentration in seawater, but not in sediment. Analysis of water-sediment exchange of PAHs showed that the direction of the net flux of PAHs was from sediment to seawater for most priority PAHs, and from water to sediment for a few HWM-PAHs.


Local and Global Electric Field Asymmetry in Photosynthetic Reaction Centers.
The origin of unidirectional electron transfer in photosynthetic reaction centers (RCs) has been widely discussed. Despite the high level of structural similarity between the two branches of pigments that participate in the initial electron transfer steps of photosynthesis, electron transfer only occurs along one branch. One possible explanation for this functional asymmetry is the differences in the electrostatic environment between the active and the inactive branches arising from the charges and dipoles of the organized protein structure. We present an analysis of electric fields in the RC of the purple bacterium Rhodobacter sphaeroides using the intrinsic carbonyl groups of the pigments as vibrational reporters whose vibrational frequency shifts can be converted into electric fields based on the vibrational Stark effect and also provide Stark effect data for plant pigments that can be used in future studies. The carbonyl stretches of the isolated pigments show pronounced Stark effects. We use these data, solvatochromism, molecular dynamics simulations, and data in the literature from IR and Raman spectra to evaluate differences in fields at symmetry-related positions, in particular at the 9-keto and 2-acetyl positions of the pigments involved in primary charge separation.


Simonart's band and facial growth in unilateral clefts of the lip and palate.
A cephalometric analysis was carried out to see if the presence of a Simonart's band at birth was associated with a detectable difference in subsequent craniofacial form. Mixed longitudinal data from 5 through 18 years of age was analyzed for 257 individuals with complete UCLP included in the Oslo CLP Growth Archive, 80 with a Simonart's band and 177 without. No major differences were detected between individuals with or without Simonart's band, though the presence of a Simonart's band was associated with a larger cranial base angle and a slightly more favorable maxillomandibular relationship. The findings are discussed in relation to embryogenesis, primary surgery, and secondary surgery. It is recommended that cephalometric studies of UCLP involving group comparisons should avoid major imbalance with respect to the proportion of individuals with a Simonart's band at birth.


Reduction of Propofol-Induced Pain through Pretreatment with Lidocaine and/or Flurbiprofen.
Pain is a well recognised complication of propofol injection. The purpose of this study was to compare the efficacy of flurbiprofen, lidocaine and a combination of the two in reducing pain on injection of propofol. Prospective, randomised, double-blind, placebo-controlled study. University hospital in Tsukuba City, Japan. 120 patients, 56 males and 64 females, aged 20-66 years, scheduled for elective plastic surgery were included. Patients received intravenously either lidocaine 20mg, flurbiprofen 50mg, both, or placebo (saline) accompanied by manual venous occlusion for 2 minutes, followed by administration of propofol 2 mg/kg into a dorsal hand vein (n = 30 in each group). A blinded researcher asked each patient to evaluate the pain score (0 = none, 1 = mild, 2 = moderate, 3 = severe) during propofol injection. The incidence and intensity of pain was less in patients receiving lidocaine (27%, pain score 0 [median]), flurbiprofen (43%, 0), or both (3%, 0) along with venous occlusion than in those receiving placebo (90%, 2) along with venous occlusion (p < 0.01). Combined lidocaine and flurbiprofen with venous occlusion was the most effective treatment (p < 0.05). No complications such as pain, oedema, wheal or flare response were observed at the injection sites within the first 24 hours after surgery. Combined lidocaine 20mg and flurbiprofen 50mg along with venous occlusion for 2 minutes was very effective for reducing pain on injection of propofol in patients scheduled for elective plastic surgery.


Localization of nucleoside phosphatases (ATPase and 5'-nucleotidase) and nuclear ribonucleoproteins in the human endometric glandular cells during the secretory phase.
Endometrial curettings from 3 healthy women between 16th and 19th d of the menstrual cycle were investigated employing ultracytochemical methods. In endometrial glandular cells ATPase and 5'-nucleotidase activities were demonstrated in the nuclei, nucleoli, and nuclear channel system (NCS), i.e., mainly in structures characterized ++as ribonucleoproteins according to the Bernhard method. The functional relationship between the NCS and the molecular biology of the endometrial glandular cell is discussed.


Functional analogue reaction systems of the DMSO reductase isoenzyme family: probable mechanism of S-oxide reduction in oxo transfer reactions mediated by bis(dithiolene)-tungsten(IV,VI) complexes.
The recent development of structural and functional analogues of the DMSO reductase family of isoenzymes allows mechanistic examination of the minimal oxygen atom transfer paradigm M(IV) + QO M(VI) O + Q with the biological metals M = Mo and W. Systematic variation of the electronic environment at the WIV center of desoxo bis(dithiolene) complexes is enabled by introduction of para-substituted phenyl groups in the equatorial (eq) dithiolene ligand and the axial (ax) phenolate ligand. The compounds [W(CO)2(S2C2(C6H4-p-X)2)2] (54-60%) have been prepared by ligand transfer from [Ni(S2C2(C6H4-p-X)2)2] to [W(CO)3(MeCN)3]. A series of 25 complexes [W(IV)(OC6H4-p-X')(S2C2(C6H4-p-X)2)2]1- ([X4,X'], X = Br, F, H, Me, OMe; X' = CN, Br, H, Me, NH2; 41-53%) has been obtained by ligand substitution of five dicarbonyl complexes with five phenolate ligands. Linear free energy relationships between E1/2 and Hammett constant p for the electron-transfer series [Ni(S2C2(C6H4-p-X)2)2]0,1-,2- and [W(CO)2(S2C2(C6H4-p-X)2)2]0,1-,2- demonstrate a substituent influence on electron density distribution at the metal center. The reactions [WIV(OC6H4-p-X')(S2C2(C6H4-p-X)2)2]1- + (CH2)4SO [W(VI)O(OC6H4-p-X')(S2C2(C6H4-p-X)2)2]1- + (CH2)4S with constant substrate are second order with large negative activation entropies indicative of an associative transition state. Rate constants at 298 K adhere to the Hammett equations log(k([X4,X']/k[X4,H]) = rho(ax)sigma(p) and log(k[X4,X']/k([H4,X']) = 4rho(eq)sigma(p). Electron-withdrawing groups (EWG) and electron-donating groups (EDG) have opposite effects on the rate such that k(EWG) > k(EDG). The effects of X' on reactivity are found to be approximately 5 times greater than that of X (rho(ax) = 2.1, rho(eq) = 0.44) in the Hammett equation. Using these and other findings, a stepwise oxo transfer reaction pathway is proposed in which an early transition state, of primary W(IV)-O(substrate) bond-making character, is rate-limiting. This is followed by a six-coordinate substrate complex and a second transition state proposed to involve atom and electron transfer leading to the development of the W(VI)=O group. This work is the most detailed mechanistic investigation of oxo transfer mediated by a biological metal.


Eosinophilic inflammation in cough variant asthma.
Eosinophils are considered to play a central pathogenetic role in asthma. We previously reported that sputum eosinophilia was observed in patients with cough variant asthma (CVA), as well as in "classic" asthma with wheezing. This study was undertaken to further investigate the involvement of eosinophils in CVA. The serum eosinophil cationic protein (ECP) level, the percentage of eosinophils in bronchoalveolar lavage (BAL) fluid, and the number of eosinophils in bronchial biopsy specimen were examined in 14 patients with CVA, 21 with classic asthma, and in seven healthy controls. For the two asthmatic groups, the clinical severity was classified with scores of 1-3. Pulmonary function and bronchial responsiveness were not significantly different between the patients with classic asthma and those with CVA. BAL, tissue eosinophil and serum ECP were all significantly increased in both classic asthma and CVA when compared with the controls but were not different between classic asthma and CVA. In both groups of asthmatics, the clinical severity significantly correlated with serum ECP and tissue eosinophils. In conclusion, eosinophilic inflammation is involved in cough variant asthma as well as in classic asthma. Anti-inflammatory treatment may be essential in patients with CVA, as in those with classic asthma.


The C-terminal half of the preS1 region is essential for the secretion of human hepatitis B virus large S protein devoid of the N-terminal retention sequence.
A large surface protein of human hepatitis B virus was expressed from a mutated S gene in which both the reported retention sequence (aa 2-19) and the C-terminal half of the preS1 region (aa 66-117) were deleted. This retention sequence-free protein was not secreted from the monkey kidney cell line COS-M6 in transient expression assays. When this large S protein was overexpressed in the presence of the major S protein, the secretion of the latter was severely inhibited. Moreover, the presence of S protein in large abundance did not facilitate the secretion of the mutated large S protein at all, indicating that it was subject to more profound retention than the wild-type large S protein. The findings that, like the wild-type large S protein, this altered protein retained some of the properties of its C-terminal S domain, and that the preS1 region was still on its surface suggested that there was no extensive alteration of the polypeptide folding. The interpretation is favored that the C-terminal half of the preS1 region plays a crucial role in the secretion of the large S protein when its N-terminal retention sequence is not present.


Combining virotherapy and angiotherapy for the treatment of breast cancer.
A breast cancer-selective oncolytic adenovirus was engineered to express antagonists of vascular endothelial growth factor (VEGF) and Notch signaling to combine direct anticancer activity with disruption of tumor-associated angiogenesis. Replication of the parental virus, AdEHE2F, is stimulated by estrogen receptor (ER), E2F1 and hypoxia, and it mediates selective lysis of breast cancer cells in vitro and in vivo. Here, we encoded soluble Flt-1 (sFlt1) and soluble Dll4 (sDll4) under control of the E3 promoter. sFlt1 (the extra-cellular domain of VEGF receptor 1) binds VEGF-A and inhibits stimulation of VEGFR2, decreasing angiogenic stimulus. Conversely, sDll4 (the extracellular domain of Delta-like 4) antagonizes Notch signaling to prevent endothelial maturation. We hypothesized that these agents might show additive or synergistic activity. In vitro, sFlt1 inhibited endothelial cell proliferation and sprouting, whereas sDll4 increased the number of vascular branchpoints. In ER-positive ZR75.1 tumors in vivo AdEHE2F showed the potent direct virotherapy with no augmentation owing to sFlt1 or sDll4; however, in ER-negative MDA-231 tumors efficacy was enhanced by encoding sFlt1 or sDll4, with survival time extending to double that of controls. There was also a dramatic decrease in the total number of tumour blood vessels, as well as the number of perfused vessels, suggesting that improved efficacy reflects combined anti-tumour and anti-vascular effects.


Tensile fatigue in bone: are cycles-, or time to failure, or both, important?
In life, bones are subjected to fatigue loading which has different frequency and amplitude components, as well as various kinds of loading modes like tension, compression, shear and combinations of them. Considerable variability is observed in fatigue results of bone, which may be caused by these experimental variables or by the bone itself. In past studies the effect of magnitude and mode of loading have been examined in standard fatigue strength (stress vs. cycles to failure) diagrams. The effect of frequency is not clear, but there is clear evidence (from Carter & co-workers) that, at least in human bone, tension "fatigue" failure was determined solely by time rather than by cycles. We sought to confirm these results in the same and a different species. We cycled human and bovine bone in tension at two frequencies: 0.5 and 5 Hz. There was no cycle number effect; the results from the tests at the two frequencies were different if plotted and analysed as a function of cycles to failure, but were not separable if plotted and analysed as a function of time to failure. In this respect bone differs from tendon, in which failure in tension is a function of both cycles and time.


[Dexmedetomidine. Pharmacokinetics and pharmacodynamics].
Dexmedetomidine is a highly selective, potent α₂-adrenoceptor agonist which was approved in 2011 by the European Medicines Agency for sedation of patients in intensive care units (ICU). Dexmedetomidine exhibits sedative as well as analgesic and anxiolytic effects. Recent studies suggest that dexmedetomidine may be an alternative to midazolam in long-term ICU sedation. This review summarizes the pharmacokinetics and pharmacodynamics of dexmedetomidine particularly in ICU patients and with special regard to covariate effects. Although dexmedetomidine is currently approved only for use in adults the pharmacokinetics and pharmacodynamics in children will also be addressed as there are numerous studies on this off-label use.


Roles of non-catalytic subunits in gbetagamma-induced activation of class I phosphoinositide 3-kinase isoforms beta and gamma.
By using purified preparations we show that nanomolar concentrations of Gbetagamma significantly stimulated lipid kinase activity of phosphatidylinositol 3-kinase (PI3K) beta and PI3Kgamma in the presence as well as in the absence of non-catalytic subunits such as p85alpha or p101. Concomitantly, Gbetagamma stimulated autophosphorylation of the catalytic subunit of PI3Kgamma (EC(50), 30 nM; stoichiometry >/=0.6 mol of P(i)/mol of p110gamma), which also occurred in the absence of p101. Surprisingly, we found that p101 affected the lipid substrate preference of PI3Kgamma in its Gbetagamma-stimulated state. With phosphatidylinositol as substrate, p110gamma but not p101/p110gamma was significantly stimulated by Gbetagamma to form PI-3-phosphate (EC(50), 20 nM). The opposite situation was found when PI-4,5-bisphosphate served as substrate. Gbetagamma efficiently and potently (EC(50), 5 nM) activated the p101/p110gamma heterodimer but negligibly stimulated the p110gamma monomer to form PI-3,4,5-trisphosphate. However, this weak stimulatory effect on p110gamma was overcome by excess concentrations of Gbetagamma (EC(50), 100 nM). This finding is in accordance with the in vivo situation, where activated PI3K catalyzes the formation of PI-3,4,5-trisphosphate but not PI-3-phosphate. We conclude that p101 is responsible for PI-4, 5-bisphosphate substrate selectivity of PI3Kgamma by sensitizing p110gamma toward Gbetagamma in the presence of PI-4,5-P(2).


Leu-enkephalin content in rat brain during prolonged treatment with imipramine or amitriptyline.
Male Wistar rats were treated with imipramine /IMI/ /2 or 10 mg/kg, p.o./ or amitriptyline /AMI/ 10 mg/kg, p.o./ by drinking water. Each drug was given once or over periods of 1, 3, 4, 6 and 9 months. Leu-enkephalin /LENK/ content was measured by radioimmunoassay in the striatum, hypothalamus and brain perfusates after different periods of the treatment with antidepressants. A single 10 mg/kg dose of IMI increased the level of LENK in the striatum and decreased it in the hypothalamus. Six months after IMI treatment the level of LENK in the striatum was decreased after a 2 mg/kg dose and increased after 10 mg/kg; in the hypothalamus a dose-dependent increase of LENK content was observed. In brain perfusates the level of LENK was decreased 3 months after IMI treatment, but highly increased after a 9-month administration. This indicates that during prolonged treatment with imipramine the central enkephalinergic activity is dynamically changed and can affect the psychopharmacological effects of IMI. After the prolonged treatment with AMI a decrease of LENK level in the striatum was observed only after 4 months of the drug administration, and no changes were seen in the hypothalamus. It is suggested that both antidepressants studied have different action on the central enkephalinergic system.


Electro-Fermentation - Merging Electrochemistry with Fermentation in Industrial Applications.
Electro-fermentation (EF) merges traditional industrial fermentation with electrochemistry. An imposed electrical field influences the fermentation environment and microbial metabolism in either a reductive or oxidative manner. The benefit of this approach is to produce target biochemicals with improved selectivity, increase carbon efficiency, limit the use of additives for redox balance or pH control, enhance microbial growth, or in some cases enhance product recovery. We discuss the principles of electrically driven fermentations and how EF can be used to steer both pure culture and microbiota-based fermentations. An overview is given on which advantages EF may bring to both existing and innovative industrial fermentation processes, and which doors might be opened in waste biomass utilization towards added-value biorefineries.


Structure and function of voltage-gated ion channels.
Voltage-gated ion channels are key molecules for the generation of electrical signals in cells. They are integral membrane proteins which are activated by a depolarized membrane potential resulting in a conformational change, allowing ions to permeate. Voltage-gated ion channels can either be inactivated from this open state by an additional conformational change which leads to a nonconducting state of the channel, or they may be deactivated by a repolarized membrane potential. Following the first successful cloning of voltage-gated ion channels in 1984 the combination of molecular biological and electrophysiological techniques has been very fruitful in the investigation of the structure and function of these membrane proteins. From these studies a molecular picture of the structural elements important for the activity of voltage-gated ion channels has been established. This has assisted in clarifying the molecular basis of the electrical excitability of cells.


Daily prognostic estimates for critically ill adults in intensive care units: results from a prospective, multicenter, inception cohort analysis.
To develop daily prognostic estimates for individual patients treated in adult intensive care units (ICU). Prospective, multicenter, inception cohort analysis. Forty-two ICUs at 40 U.S. hospitals with > 200 beds including 20 ICUs in tertiary care centers with major teaching activities. A consecutive sample of 17,440 ICU admissions. A series of multivariate equations were developed using the patient's primary reason for ICU admission, age, chronic health status, treatment before ICU admission, admission Acute Physiology Score, current day Acute Physiology Score, and change between the current and previous day's Acute Physiology Score. The equations were used to create daily risk predictions and cross-validated within the 17,440-patient sample. The single most important factor determining daily risk of hospital death during each of the initial 7 days of ICU care was the current day's Acute Physiology Score of the Acute Physiology and Chronic Health Evaluation (APACHE) III score. The admission Acute Physiology Score and change from previous to current day's Acute Physiology Score were also important, as were ICU admission diagnosis, age, chronic health status, and treatment before ICU admission. Equations incorporating these risk factors had receiver operating characteristics areas ranging from 0.9 on the first ICU day to 0.84 for patients remaining in the ICU for 7 days. The percent of cases with cross-validated predicted risks over 90% increased from 2.3% (n = 406) of cases on day 1 to 9% of all patients remaining in the ICU on ICU day 7 (n = 218). The 1,033 patients who had a daily risk estimate of > 90% during any of their initial 7 ICU days had a 90% mortality rate and represented 47% of all ICU deaths and 31% of the total number of hospital deaths. Equations using initial and repeated physiologic measurements provide a high degree of explanatory power for subsequent hospital mortality rate. These daily prognostic estimates deserve evaluation for their potential role in improving the process and outcome from clinical decision-making.


The factor XIII Val34Leu polymorphism: is it protective against idiopathic venous thromboembolism?
The substitution of leucine for valine at amino acid position 34 of the factor XIII gene is commonly referred to as FXIII Val34Leu polymorphism. The homozygous leucine/leucine genotype has been reported to confer protection against venous thromboembolism, but previous studies have not evaluated a population limited to those with idiopathic venous thromboembolism. The primary objective of the study was to determine whether the FXIII Val34Leu polymorphism is independently associated with the occurrence of idiopathic venous thromboembolism. We prospectively enrolled consecutive patients with at least one objectively confirmed idiopathic venous thromboembolism. Friends of cases were recruited as controls and matched to cases by sex, ethnicity, and age. All participants were tested for the FXIII Val34Leu polymorphism in addition to several well-known thrombophilias. Data from 309 cases and 306 controls were analyzed. The FXIII leucine/leucine genotype was present in 4.9% of cases and 6.5% of controls. An adjusted odds ratio of 0.59 (95% confidence interval, 0.25-1.38) was found for the recessive model and 0.69 (95% confidence interval, 0.46-1.02) for the dominant model. Our results do not support an independent association of the FXIII Val34Leu polymorphism with idiopathic venous thromboembolism in our Caucasian Canadian study population.


["Damage, not age, is what makes a person old": ageing and health in rural males].
To analyze the social factors associated with the health status of elderly men, 60 years and older, who live in poverty in the rural areas of Mexico. A cross-sectional, descriptive study was conducted between February and October 2002, in a convenience sample of 392 elderly men residing in rural areas of the states of Guerrero, Morelos and Jalisco states. A validated questionnaire was applied to collect data on sociodemographic characteristics, general wellbeing, health problems, food consumption, and some indicators of mental health, personal strength and social support. Data analysis was performed with the SPSS v. 11. software, to obtain chi-squared tests; food intake measures were analized with one-way ANOVA. Study subjects were married or were widowers and had six children on average. A higher proportion of the elderly men of Morelos state reported to have suffered more illnesses and a higher consumption of alcohol when compared to the other two state groups. Sixty percent of the men in the study used both home remedies and medication for their health problems. More than one half of them did not receive adequate social support from their families. The results of this study suggest that the process of ageing among rural elderly men is perceived as a burden, mainly because of the context of poverty in which they live. The lack of appropriate income and access to health services through adequate pension and retirement plans for the elderly poor is a problem that requires immediate attention.


Insulin treatment and clinical outcomes in patients with diabetes and heart failure with preserved ejection fraction.
Insulin causes sodium retention and hypoglycaemia and its use is associated with worse outcomes in heart failure (HF) with reduced ejection fraction. We have investigated whether this is also the case in HF with preserved ejection fraction (HFpEF). We examined the association between diabetes/diabetes treatments and the risk of the primary composite of cardiovascular death or HF hospitalization, as well as other outcomes in adjusted analyses in CHARM-Preserved (left ventricular ejection fraction ≥ 45%), I-Preserve and TOPCAT (Americas) pooled. Of 8466 patients, 2653 (31%) had diabetes, including 979 (37%) receiving insulin. Patients receiving insulin were younger, had a higher body mass index, prevalence of ischaemic aetiology, N-terminal pro-B-type natriuretic peptide and use of diuretics, worse New York Heart Association class and signs and symptoms, and worse quality of life and renal function, compared to patients with diabetes not on insulin. Among the 1398 patients with echocardiographic data, insulin use was associated with higher left ventricular end-diastolic pressure and more diastolic dysfunction than in other participants. The primary outcome occurred at a rate of 6.3 per 100 patient-years in patients without diabetes, and 10.2 and 17.1 per 100 patient-years in diabetes patients without and with insulin use, respectively [fully adjusted hazard ratio (aHR) insulin-treated diabetes vs. other diabetes: 1.41, 95% confidence interval (CI) 1.23-1.63, P < 0.001]. The adjusted HR is 1.67 (95% CI 1.20-2.32, p = 0.002) for sudden death (insulin-treated diabetes vs. other diabetes). Insulin use is associated with poor outcomes in HFpEF. Although we cannot conclude a causal association, the safety of insulin and alternative glucose-lowering treatments in HF needs to be evaluated in clinical trials.


The HLA-C*05 family allele - C*05:142.
The sequencing of exons 2-7 of a likely new HLA-C*05 allele identified the second example of HLA-C*05:142, in a male UK European, within a few months of the first example being found in Germany. C*05:142 differs from C*05:01:01:01 by a single base (395G>C) in exon 3 resulting in an amino acid substitution of R108P. Comprehensive serological HLA-Cw5 typing, using 19 antisera, indicated that C*05:142 encodes a "normal" Cw5 specificity. Failure to identify the involvement of position 108 in published HLA-C epitopes supported this assertion. The likely HLA class I C*05:142-bearing haplotype is A*02:01~C*05:142~B*44:02. This new allele has a maximum frequency of 0.00001, in 34,743 sequenced-based typed subjects, contrasting with that of C*05:01 (allele frequency 0.10441), in our local, largely UK European, blood donors.


Sweat mechanisms and dysfunctions in atopic dermatitis.
Skin barrier dysfunction is inherent to atopic dermatitis (AD), causing dryness, irritation, and increased permeability to irritants, allergens and pathogens. Eccrine sweat functions as part of the skin's protective barrier. Variations in sweat responses have been observed in patients with AD, and altered sweat composition and dynamics are under-recognized as important factors in the disease cycle. This review discusses the role that sweat plays in the pathogenesis of AD, examines evidence on abnormal sweat composition, secretion, and neuro-immune responses to sweat in atopic skin, and highlights the value of sweat management.


Dendritic cell subtypes in mouse lymphoid organs: cross-correlation of surface markers, changes with incubation, and differences among thymus, spleen, and lymph nodes.
Freshly isolated, mature dendritic cells (DC) from mouse lymphoid organs were analyzed by immunofluorescent labeling and flow cytometry to determine the number of discrete subpopulations and to assess possible lineage markers. The permanence of surface markers was then determined by overnight culture of the DC. Three DC subtypes were discerned, CD8alpha- DEC-205-, CD8alpha+ DEC-205+, and CD8alpha- DEC-205+, with different tissue distributions. The majority of DC expressed high levels of class II MHC, expressed CD11c, and expressed the costimulator molecules CD80, CD86, and CD40; CD80 and CD40 were further up-regulated on culture. DC also expressed low levels of L-selectin that were up-regulated on culture. Thymus contained predominantly CD8alpha+ DEC205+ CD11b- DC, resembling a major subpopulation of DC in other tissues but unique in expressing BP-1. Spleen contained predominantly two DC populations in equal proportions: one CD8alpha+ DEC-205+ CD11b- as in the thymus, and the other CD8alpha- DEC-205- CD11b+. Lymph nodes contained the same two DC populations as in spleen, but in addition a third population of CD8alpha- DEC-205+ CD11b- DC. The CD8alpha expression of splenic DC subpopulations did not change on culture. Although DEC-205 was up-regulated on culture so all DC became positive, the difference in the level between subpopulations was maintained. However, CD11b was up-regulated on culture, so all subpopulations became positive and finally expressed equivalent levels. Some aspects of this complex, but discrete, pattern of surface marker expression can be correlated with differences in lineage origin and functional activity of the DC.


Calcium movements in aortae from arthritic rats.
40Ca content, 45Ca uptake, influx and efflux were measured in aortae from arthritic rats. 40Ca content measured by atomic absorption spectrometry was higher in aortae from arthritic than from normal controls. 45Ca uptake, inflow and outflow were also enhanced in aortae from arthritic rats whether under basal or stimulated conditions (e.g. in the presence of high potassium or noradrenaline). Verapamil failed to inhibit basal 45Ca uptake but normally inhibited 45Ca inflow stimulated by high potassium or noradrenaline in both aortic preparations. No histological difference was detected by optical microscopy between normal and arthritic aortae. It is concluded that aortae from adjuvant arthritic rats are apparently characterized by a higher intracellular Ca++ content resulting from enhanced Ca++ inflow through at least three Ca++ pathways. This higher intracellular content may explain why aortae from arthritic rats are less dependent on extracellular Ca++ than aortae from normal rats when stimulated by agonists like serotonin and noradrenaline.


Precise placement of lag screws in operative treatment of trochanteric femoral fractures with a new guide system.
We assessed the accuracy of a new guide system that we developed to place lag screws in the proper position with the minimum number of attempts for operative treatment of trochanteric femoral fractures. A total of 55 consecutive trochanteric femoral fractures were treated with a cephalomedullary nail. The first 27 consecutive patients were treated with the standard operation (group A), while the new guide system was used in the last 28 consecutive patients (group B). The numbers of attempts to place K wires and the duration of surgery were noted. Accuracy of lag screw placement was evaluated by measuring the angle of deviation from the central axis of the femoral head. Deviation values ranged from -11̊ to +15̊ for the 27 cases in group A, with a median absolute deviation of 8̊±6̊. That in the 28 cases after the introduction of the new guide system (group B) ranged from -5̊ to +6̊, with a median absolute deviation of 0.5̊±3̊ (P<0.001). The total numbers of attempts to place lag screws and mean operation time decreased significantly after introduction of the new guide system (P<0.001). With this new guide system, we are able to insert lag screws successfully in the optimal position even in most unstable fractures. The present study indicated that this new guide system and nail facilitate accurate placement of lag screws in the appropriate position with the minimum number of attempts.


Ruminative coping with depressed mood following loss.
In a longitudinal study of 253 bereaved adults, people with poorer social support, more concurrent stressors, and higher levels of postloss depression reported more rumination than people with better social support, fewer stressors, and lower initial depression levels. Women reported more rumination than men. People with a ruminative style at 1 month were more likely to have a pessimistic outlook at 1 month, which was associated with higher depression levels at 6 months. People with a more ruminative style were more depressed at 6 months, even after controlling for initial depression levels, social support, concurrent stressors, gender, and pessimism. Additional stressors and high depression scores at 1 month were also associated with higher levels of depression at 6 months.


Ischemic preconditioning and nicotinamide in spinal cord protection in an experimental model of transient aortic occlusion.
Spinal cord injury is a devastating complication after aortic surgery. The aim of the present study is to examine the effects of ischemic preconditioning (IPC) and nicotinamide containing perfusate in transient aortic occlusion in the rat. Thirty-two male Spraque-Dawley rats under general anesthesia were randomly assigned to four groups (n=8 in each group). The infrarenal aortas were clamped for 45 min. Groups were as follows: Group 1, undergoing occlusion but receiving no treatment. Group 2, had 5 min of IPC before occlusion. Group 3, received nicotinamide (0.2 ml/l) during the transient occlusion. Group 4, received combined IPC (5 min) and nicotinamide infusion during the transient occlusion. The rats were then allowed for recovery and were tested for their neurological status. All animals were sacrificed at the end of the 48 h and spinal cords also examined histologically. Anti- poly (ADP-ribose) polymerase p85 fragment pAb was used as an immunohistochemical marker for detection of apoptosis. In 24 h paraplegia represented as grade 0 and 1 occurred in six animals in Group 1 and two animals in Groups 2 and 3 and one in Group 4. In 48 h six animals in Group 1 and only one animal in Groups 2 and 3 showed a paraplegia. The incidence of neurologic deficit was significantly reduced in animals who had IPC and nicotinamide infusion (P<0.05). At 48 h, combined IPC and nicotinamide showed a significant benefit compared to nicotinamide but not to the IPC alone. Histologic examination of the spinal cords revealed that a neuronal necrosis contributes to acute spinal cord degeneration after a period of aortic occlusion and both nicotinamide and IPC have protective effects against neuronal necrosis. No difference was found among the groups. Both IPC and nicotinamide are beneficial in protection against neurological damage in transient aortic occlusion. IPC alone as expected is significantly beneficial both at 24 and 48 h compared to controls. At 24 h combined nicotinamide and IPC show significant benefit compared to only nicotinamide, but this difference is not maintained at 48 h.


Prediabetes: the importance of early identification and intervention.
Prediabetes is a state of abnormal glucose homeostasis characterized by the presence of impaired fasting glucose, impaired glucose tolerance, or both. Individuals with prediabetes are at increased risk for type 2 diabetes, compared with individuals with normal glucose values (normal fasting plasma glucose, < 100 mg/dL [5.6 mmol/L]). The increased risk for cardiovascular disease in prediabetes is multifactorial, with etiologies including insulin resistance, hyperglycemia, dyslipidemia, hypertension, systemic inflammation, and oxidative stress. The preferred treatment is intensive lifestyle management and aggressive pharmacologic therapies directed toward individual coronary heart disease risk factors. The use of antihyperglycemic agents in this setting is a topic of intense debate. This review discusses the pathophysiology of prediabetes and its clinical implications, highlighting the importance of early identification and intervention.


[Epidemiological and clinical characteristics of 705 salivary glands neoplasms].
The epidemiological data concerning the rare group of tumors derived from salivary glands recorded in the National Cancer Registry is insufficient because it records only malignant salivary glands tumors. The epidemiological and clinical characteristics of 699 patients with salivary glands tumors (n=705). The data were retrieved from ENT Department District Hospital in Kielce (01.09.1989-28.02.2001) and from Department of Otolaryngology Head and Neck Surgery Holy Cross Cancer Centre in Kielce (01.03.2001-31.12.2008). In the analyzed group of 699 patients with 705 salivary glands tumors women predominated, consisting 54,2% of all group. The average age in group of malignant tumors was higher than in nonmalignant group. The risk of malignant neoplasms development increased with patient age. In the analyzed group of 705 salivary glands tumors the nonmalignant neoplasms dominated-78,3%. Out of all cases, 547 (77,6%) were localized in the parotid gland, 80 (11,3%) in submandibular gland and 78 (11,1%) in minor salivary glands. Nonmalignant tumors were more frequent in the parotid gland (82,8%) and submandibular gland (71,3%), whereas in minor salivary glands nonmalignant and malignant neoplasms the occurrence was nearly the same. In general-the smaller the salivary gland, the risk of development malignant tumors was higher. In group of nonmalignant salivary gland tumors two histopathological types dominated - pleomorphic adenoma and Warthin's tumor, which comprised 91,8% of the whole group. In the group of 153 malignant salivary gland tumors the most common histopathology were - adenoid cystic carcinoma, mucoepidermoid carcinoma and adenocarcinoma. In the analyzed period of 20 years' time, the incidence of salivary glands tumors increased with high siginificance, both for nonmalignant, as well malignant tumors.


Distribution and source recognition of polycyclic aromatic hydrocarbons in the sediments of Hsin-ta Harbour and adjacent coastal areas, Taiwan.
Thirty-three sediment samples from Hsin-ta Harbour and neighboring coastal areas were analyzed by GC-MS for polycyclic aromatic hydrocarbons (PAHs). Total concentrations of 30 analyzed parental and alkylated PAHs ( summation operator PAH) varied from 98.1 to 3382 ng/g dry weight. MP/P (methylphenanthrenes/phenanthrene) values larger than 2 coincided with very low P/A (phenanthrene/anthracene) values at inner harbour stations, revealing that a significant portion of low molecular weight PAHs are probably from petrogenic pollution sources, specifically, illegal disposal of used motor oil. The 4,6-dimethyldibenzothiophene/3,6-dimethylphenanthrene (4,6-C(2)D/3,6-C(2)P) ratio is found to be more useful than the MP/P ratio in tracing petrogenic PAHs from the inner harbour area to the adjacent coastal environment. In addition, according to hierarchical cluster analysis, collected sediments cluster in three major groups, Off-shore Group, Near-shore Group and Inner Harbour Group. Three diagnostic ratios, 4,6-C(2)D/3,6-C(2)P, PER/ summation operator PAH (perylene to summation operator PAH) and BaA/CHR (benzo(a)anthracene/chrysene), representing petrogenic, biogenic and pyrogenic origins, are found to be effective in differentiating and characterizing sediments among the groups in this study. Enrichment of pyrogenic and petrogenic PAHs in sediments collected exhibits mixing or dilution, spatially, by biogenic (or natural) PAHs.


Thoracoscopic resection of an esophageal cyst in a 4-year-old girl.
Thoracoscopic resection of a 4-cm esophageal cyst was performed in a young child. The patient tolerated the procedure well with little chest wall trauma, and she was discharged on the second post-operative day. At 1-month follow-up, there were no associated complications.


Structure and stability effects of the mutation of glycine 34 to serine in Rhodobacter capsulatus cytochrome c(2).
Gly 34 and the adjacent Pro 35 of Rhodobacter capsulatus cytochrome c(2) (or Gly 29 and Pro 30 in vertebrate cytochrome c) are highly conserved side chains among the class I c-type cytochromes. The mutation of Gly 34 to Ser in Rb. capsulatus cytochrome c(2) has been characterized in terms of physicochemical properties and NMR in both redox states. A comparison of the wild-type cytochrome c(2), the G34S mutation, and the P35A mutation is presented in the context of differences in chemical shifts, the differences in NOE patterns, and structural changes resulting from oxidation of the reduced cytochrome. G34S is substantially destabilized relative to wild-type (2.2 kcal/mol in the oxidized state) but similarly destabilized relative to P35A. Nevertheless, differences in terms of the impact of the mutations on specific structural regions are found when comparing G34S and P35A. Although available data indicates that the overall secondary structure of G34S and wild-type cytochrome c(2) are similar, a number of both perturbations of hydrogen bond networks and interactions with internal waters are found. Thus, the impact of the mutation at position 35 is propagated throughout the cytochrome but with alterations at defined sites within the molecule. Interestingly, we find that the substitution of serine at position 34 results in a perturbation of the heme beta meso and the methyl-5 protons. This suggests that the hydroxyl and beta carbon are positioned away from the solvent and toward the heme. This has the consequence of preferentially stabilizing the oxidized state in G34S, thus, altering hydrogen bond networks which involve the heme propionate, internal waters, and key amino acid side chains. The results presented provide important new insights into the stability and solution structure of the cytochrome c(2).


Evidence of the pressure-induced conductivity switching of yttrium-doped SrTiO3.
The electrical transport properties of undoped and yttrium-doped strontium titanate (Sr(Ti1 - x Y x )O3 - δ , x = 0, 0.02) under high pressure were investigated with in situ impedance spectroscopy measurements. A pressure-induced conductivity switching for undoped and 2 mole% Y-doped strontium titanate is observed at around ~10.0 and 7.0 GPa respectively, which are caused by a cubic to tetragonal I4/mcm phase transition. The decrease of the phase transition point of 2 mole% Y-doped strontium titanate can be attributed to larger Y(3+) atoms occupying the B-site and the creation of more oxygen vacancies, which lead to octahedra tilting and symmetry breaking. The results of the voltage-bias dependence of grain-boundary impedance of undoped and 2 mole% Y-doped strontium titanate at different pressures revealed that Schottky-type potential barriers formed at grain boundaries are the key factor for the accumulation of oxygen vacancy at the interface under pressure.