Systematic review of laparoscopic surgery for colorectal malignancy.
We set out to evaluate the current literature on the use of laparoscopic surgery for malignant colorectal disease and identify its place in current practice. We performed a systematic review of the literature that included papers published from January 1991 to March 1997. Inclusion criteria were used to select the most robust studies. The quality of each study was assessed against predefined criteria and weighted according to hierarchy of evidence and sample size. The published literature was found to be low in the hierarchy of evidence. Of the 157 studies located, only 42 papers were found to be of sufficiently high quality to be included in the review. Only 13 of these 42 papers concentrated specifically on malignant colorectal disease. We noted the following findings: The average age of patients was 63.2 years. The most frequently reported contraindication to laparoscopic surgery was obesity. Conversion rate to open procedure varied between 1.5% and 48%. The most common postoperative complication was wound infection. Thirty-day mortality varied between 0 and 5.1%. Disease stage and pathology were poorly reported. Patient recovery benefits varied. It was not possible to identify the effectiveness, safety, survival outcome, or cost of laparoscopic surgery for colorectal malignancy in comparison to open surgery. Six years after the first report of laparoscopic surgery, studies low in the hierarchy of evidence continue to be reported. This reflects a lack of control following the introduction of this new technology. The majority of reports continue to be feasibility studies. The variable nature and content of the literature demonstrate the lack of standardization and the absence of an agreed core minimum data set. The benefit of laparoscopic surgery for malignant colorectal disease remains unclear. Until the mechanisms of port site recurrences are elucidated and long-term data on survival outcomes become available, laparoscopic surgery for malignant disease should be carried out only in the context of a large, multicenter randomized controlled trial.


Neuroendocrine mechanisms mediating the suppression of circulating testosterone levels associated with chronic stress in male rats.
Neuroendocrine mechanisms involved in the reduction of testosterone (T) levels induced by the chronic surgical stress of s.c. gauze implantation were investigated in male rats. The reduction resulted from a decline in T secretion and not an increase in clearance of the hormone from the circulation. In most cases, the decrement was accompanied by a reduction in LH levels, indicating that decreased LH stimulation is the primary factor mediating the drop in T levels. The suppressive effect of surgical stress on LH and T levels was apparently not mediated by the pituitary-adrenal system.


Quantitative characterization of direct P-glycoprotein inhibition by St John's wort constituents hypericin and hyperforin.
The ATP-binding cassette transporter P-glycoprotein (P-gp) exerts a critical role in the systemic disposition of, and exposure to, lipophilic and amphipathic drugs, carcinogens, toxins and other xenobiotics. The ability of P-gp to transfer a wide variety of structurally unrelated compounds from the cell interior across the membrane bilayer remains intriguing. Since natural product chemicals in the widely consumed St John's wort appear to exert antidepressant effects by an unknown mechanism, the constituents are frequently studied for interactions with various biomacromolecules as well as cytotoxins or isolated cells. The drug interactions caused by this widely used herbal remedy are under-appreciated. Various clinical interactions have been observed upon the co-administration of St John's wort, and P-gp and CYP3A4 have been indicted as the cause. We characterized several St John's wort constituents for their interaction with P-gp and their specific effects on the P-gp export activity of several marker substrates. Two of these constituents, hyperforin and hypericin, inhibit the active efflux of the fluorescent markers daunorubicin (IC(50) approximately 30 microM) and calcein-AM. Herein, we show in-vitro results that can both explain the competing clinical observations of initial elevated exposure of P-gp substrate drugs (P-gp inhibition) followed by under-exposure (P-gp induction) when St John's wort is co-administered, and provide a further warning against unchecked co-administration of drugs with St John's wort.


Bioaccessibility of bioactive amines in dark chocolates made with different proportions of under-fermented and fermented cocoa beans.
The influence of under-fermented (UF) cocoa (0 to 65 %) on bioactive amines in chocolate and their in vitro bioaccessibility was investigated. The same amines were found in all treatments; however, treatments were divided into two groups regarding total amines [0 & 20 % UF (34 mg/kg) and 35 to 65 % UF (17 mg/kg)] and phenolic levels [lower and higher, respectively]. Serotonin, tyramine, putrescine, cadaverine, agmatine and phenylethylamine were higher in chocolate with ≤ 20 % UF cocoa. Histamine and spermidine were not affected. Digestibility studies indicated that low levels of amines were present in the oral phase. Gastric digestion was effective in releasing tyramine, spermidine and phenylethylamine from conjugates. Serotonin and agmatine were not detected after in vitro digestion of chocolate with ≥ 35 % UF cocoa. Histamine was released during in vitro intestinal digestion. By adding different proportions of UF cocoa during chocolate production, the levels and bioaccessibility of amines can be modulated.


CUBIC-f: An optimized clearing method for cell tracing and evaluation of neurite density in the salamander brain.
Although tissue clearing and subsequent whole-brain imaging is now possible, standard protocols need to be adjusted to the innate properties of each specific tissue for optimal results. This work modifies exiting protocols to clear fragile brain samples and documents a downstream pipeline for image processing and data analysis. We developed a clearing protocol, CUBIC-f, which we optimized for fragile samples, such as the salamander brain. We modified hydrophilic and aqueous' tissue-clearing methods based on Advanced CUBIC by incorporating Omnipaque 350 for refractive index matching. By combining CUBIC-f, light sheet microscopy and bioinformatic pipelines, we quantified neuronal cell density, traced genetically marked fluorescent cells over long distance, and performed high resolution characterization of neural progenitor cells in the salamander brain. We also found that CUBIC-f is suitable for conserving tissue integrity in embryonic mouse brains. CUBIC-f shortens clearing and staining times, and requires less reagent use than Advanced CUBIC and Advanced CLARITY. CUBIC-f is suitable for conserving tissue integrity in embryonic mouse brains, larval and adult salamander brains which display considerable deformation using traditional CUBIC and CLARITY protocols.


The Prevalence of Patient Aggression Toward Dental Students at a Canadian University Teaching Clinic.
Studies show concerning rates of occupational violence against oral health care workers, but few studies of this nature have been conducted on dental students in university clinics. We surveyed 3rd-, 4th- and 5th-year dental students in the 2020-2021 academic year at the dental teaching clinic of the University of Montreal, using a 17-item self-report questionnaire exploring 4 types of aggression: physical, verbal, reputational and sexual. Of 239 students, 45 (19%) responded to the online questionnaire, and 28 (62% of respondents) reported some form of aggression in the previous year. Verbal aggression and sexual aggression were each reported by 21 (47%) students. No differences were found between rates of aggression based on ethnicity. Women (74%) reported higher rates of aggression than men (47%), although this difference did not reach statistical significance. Of the 6 students who said they speak a language other than French (the workplace language) at home, 5 (83%) reported experiencing sexual aggression. Most students surveyed reported experiencing some form of patient aggression in the past year. The most common forms of aggression were verbal and sexual. Women and students who speak a language other than French at home may be particularly vulnerable to patient aggression in the clinical setting. This study has implications for dental education and points to the need for training and new solutions to prevent and respond to patient aggression at university dental clinics.


Comparative study of using different materials as bacterial carriers to treat hydrogen sulfide.
The use of support media for the immobilization of microorganisms is widely known to provide a surface for microbial growth and protect the microorganisms from inhibitory compounds. In this study, molecular sieve, granular porous carbon, and ferric oxide desulfurizer, immobilized with autotrophic bacteria capable of oxidizing ferrous iron to ferric iron, were developed to treat hydrogen sulfide (H(2)S). Their corresponding bioreactors were referred to as BMS, BPC, and BFO, respectively. H(2)S loading, gas retention time, hydrogen ion, and aluminous, ferric, and ferrous iron concentrations of recycling effluents were evaluated. Thermogravimetric analysis, Brauner-Emmett-Teller method, and scanning electron microscopy were used to characterize packing materials. Results showed that the elimination capacity was in the order of BFO > BPC > BMS. This study suggested that the material characteristics progressively influenced the deodorization capacities of bioreactors. H(2)S was oxidized into elemental sulfur and oxidized sulfur species, according to differences of carriers. Furthermore, this study revealed the potential application of simultaneously treating of H(2)S under extremely acidic conditions.


Fondaparinux sodium: a review of its use in the treatment of acute venous thromboembolism.
Fondaparinux sodium (fondaparinux) is a synthetic sulfated pentasaccharide anticoagulant developed from the antithrombin binding moiety of heparin. Through the activation of antithrombin it inhibits Factor Xa, the activation of thrombin, and the subsequent coagulation cascade. Fondaparinux is approved in Europe and the US for the treatment of acute venous thromboembolism (VTE), including both deep vein thrombosis (DVT) and pulmonary embolism (PE), when used in conjunction with warfarin. In phase III clinical trials, subcutaneous fondaparinux was noninferior to subcutaneous enoxaparin or intravenous unfractionated heparin (UFH) in the prevention of recurrent symptomatic VTE in patients with acute DVT and PE, respectively, and equally well tolerated. It thus provides a valuable alternative to UFH and low-molecular weight heparins in the treatment of acute VTE, particularly in the outpatient setting.


[Cross-reacting intraspecific antigens of Neisseria meningitidis. I. The isolation, immunochemical and serological characteristics of the cross-reacting antigens of N. meningitidis serogroup A].
New data on the cross-reacting antigen of N. meningitidis, serogroup A, are presented. A complex of antigens has been isolated by treatment with tryptone X-100, ethanol precipitation and the subsequent treatment with trichloroacetic acid. The immunological analysis of the isolated preparation has shown that the proteinaceous part of the biopolymer contains 7 polypeptide fragments; of these, one fragment with a molecular weight of 31000 daltons has been found to constitute 49, 15% of all polypeptide fragments. The evaluation of the serological properties of this preparation in the precipitation test and the passive hemagglutination test has revealed that the preparation contains various cross-reactive antigenic determinants. Polyvalent erythrocyte diagnosticum obtained on the basis of this preparation permits the detection of antibodies to meningococci irrespective of their serogroup.


Reading Speed as an Objective Measure of Improvement Following Vitrectomy for Symptomatic Vitreous Opacities.
There is currently no objective measure of the visual deficits experienced by patients with symptomatic vitreous opacities (SVOs) that would also correlate with the functional improvement they report following vitrectomy. This study aims to determine whether reading speed can be used as a reliable outcome measure to assess objectively the impact of both SVOs and vitrectomy on patients' visual performance. Twenty adult patients seeking surgery for SVO were included. Measures of visual function were obtained before and after vitrectomy using the Early Treatment Diabetic Retinopathy Study acuity chart, the National Eye Institute Visual Function Questionnaire, and the MNREAD acuity chart. In patients with nonopacified lenses (n = 10), maximum reading speed increased significantly from 138 to 159 words per minute after complete removal of SVOs by vitrectomy (95% confidence interval, 14-29; P < .001). Reading speed is impaired with SVOs and improves following vitrectomy in phakic and pseudophakic eyes with clear lenses. Reading speed is a valid objective measure to assess the positive effect of vitrectomy for SVOs on near-distance daily life activities. [Ophthalmic Surg Lasers Imaging Retina. 2020;51:456-466.].


Review of the use of high potencies in basic research on homeopathy.
The HomBRex database includes details of about 1500 basic research experiments in homeopathy. A general overview on the experiments listed in the HomBRex database is presented, focusing on high dilutions and the different settings in which those were used. Though often criticised, many experiments with remedies diluted beyond Avogadro's number demonstrate specific effects. A total of 830 experiments employing high potencies was found; in 745 experiments of these (90%), at least one positive result was reported. Animals represent the most often used model system (n=371), followed by plants (n=201), human material (n=92), bacteria and viruses (n=37) and fungi (n=32). Arsenicum album (Ars.) is the substance most often applied (n=101), followed by Sulphur (Sulph.) and Thuja (Thuj.) (n=65 and 48, respectively). Proving, prophylactic and therapeutic study designs have all been used and appear appropriate for homeopathy basic research using high dilutions. The basic research data set to support specific effects unique to high dilutions and opposite to those observed with low dilutions is, to date, insufficient.


Alterations of ion-dependent ATPase activities in the brain of Singi fish, Heteropneustes fossilis (Bloch), by triiodothyronine.
The activities of Na+K(+)- and Mg(2+)-ATPases in mitochondrial, microsomal, and cytosolic fractions of Singi fish (Heteropneustes fossilis Bloch) brain were investigated after injections of various doses (0.012, 0.025, 0.05, and 0.10 micrograms/g) of triiodothyronine (T3) for 3 consecutive days. Both ATPases were found in the mitochondrial and microsomal fractions. The cytosolic fraction showed only Mg(2+)-ATPase activity. Mitochondrial Na+K(+)-ATPase activity increased to almost the same level in fish treated with 0.025, 0.05, or 0.10 micrograms of T3/g, while the T3 dose of 0.012 micrograms/g was ineffective in this respect. Microsomal Na+K(+)-ATPase activity increased to about the same level with all of the doses of T3 used. No detectable amount of Na+K(+)-ATPase was found in the brain cytosolic fraction. Mitochondrial Mg(2+)-ATPase activity was enhanced with 0.025, 0.05, and 0.10 micrograms of T3/g. The last dose, however, produced a higher increase in activity than the other two doses. Surprisingly, microsomal and cytosolic Mg(2+)-ATPase activity was not increased by T3 treatment. Although T3 concentrations rose sharply after each T3 injection, the serum T3 level in T3-injected fish was not different from that in the control as observed on the fourth day. The T3-induced rise of Na+K(+)- and Mg(2+)-ATPase activities was inhibited by cycloheximide treatment. Immersion of Singi fishes in thiourea significantly reduced brain Na+K(+)-ATPase activity in microsomal and mitochondrial fractions but decreased Mg(2+)-ATPase activity only in the mitochondrial fraction. Three consecutive daily injections of T3 (0.10 micrograms/g) into the thiourea-treated fishes increased their ATPase activities even beyond the control level.(ABSTRACT TRUNCATED AT 250 WORDS)


The major mutation in the RMRP gene causing CHH among the Amish is the same as that found in most Finnish cases.
Cartilage-hair hypoplasia (CHH), or McKusick type metaphyseal chondrodysplasia, was originally described in the Old Order Amish in the United States and subsequently found to be unusually frequent among Finns. The major mutation causing CHH in Finns is a 70A --> G nucleotide substitution in the RMRP gene, which encodes the untranslated RNA that is a component of mitochondrial RNA-processing endoribonuclease. Here we report that the same mutation is the most frequent one, perhaps the only one, in the Amish population in which CHH was first characterized. The fact that the mutation segregates with the same major haplotype in these two populations and others suggests that it is very ancient. Unlike some other ordinarily rare recessive disorders that are limited in their high frequency to a single Amish deme (subisolate), e.g., Ellis-van Creveld syndrome, CHH occurs in high frequency in at least three distinct Amish demes, indicating, along with genealogic data, that there were multiple heterozygotes among the founders, as proposed by McKusick et al. [1965: Bull Johns Hopkins Hosp 116:231-272].


Primary herpes simplex virus type 1 infection with acute liver failure in solid organ transplantation: Report of three cases and review.
Herpes virus infections is not uncommon in solid organ transplantation patients. We report 3 cases with primary Herpes simplex virus type-1 (HSV1) infection with acute liver failure (ALF). This is a rare and potentially fatal entity that could be a donor-derived infection. Although the initial clinical presentation is non-specific, it should be considered as a differential diagnosis in HSV-negative serology patients with liver failure and empirical treatment must be started in combination with a drastic reduction of immunosuppression. A strategy of HSV prophylaxis for pre-transplant HSV seronegative patients must be stablished in order to reduce the risk of clinical disease.


Comparative survival analysis between idiopathic pulmonary fibrosis and chronic hypersensitivity pneumonitis.
Chronic hypersensitivity pneumonitis (CHP) is an interstitial lung disease with limited treatment response and bad prognosis. Sometimes it is indistinguishable from idiopathic pulmonary fibrosis (IPF) becoming one of the main differential diagnosis. The aim of our study is to compare survival and functional decline between these two entities. Survival and functional decline more than 10% in FVC were compared using Kaplan Meier (KM) method between patients with CHP and IPF. Cox proportional hazard analysis was used to identify independent predictors of survival and functional decline. 146 patients were included, 54 with CHP and 92 with IPF. KM rate for 2 years survival was 0.71 (CI 95% 0,6-0,8) for CHP group and 0,83 (CI 95% 0,66 - 0,92) for IPF (p=0,027). Nevertheless this difference disappeared using Cox proportional hazard analysis, the adjusted HR for survival among CHP patients was 0,53 (CI 95% 0,25-1,15) (p=0,11). There was no difference in functional evolution between the two groups. KM rate for a decline more than or equal to 10% was 0,64 for CHP (CI 95% 0,43-0,79) and 0,78 for IPF (IC 95% 0,6-0,88) (p=0,22). This observation did not change after using Cox proportional hazard analysis. Our study shows that both IPF and CHP are fibrosing interstitial diseases with a similar evolution and survival. It might be possible that therapeutic approach in patients with CHP should change in the light of these observations.


Development of an injectable alginate-collagen hydrogel for cardiac delivery of extracellular vesicles.
Extracellular vesicles (EVs) are nanosized particles with attractive therapeutic potential for cardiac repair. However, low retention and stability after systemic administration limit their clinical translation. As an alternative, the combination of EVs with biomaterial-based hydrogels (HGs) is being investigated to increase their exposure in the myocardium and achieve an optimal therapeutic effect. In this study, we developed and characterized a novel injectable in-situ forming HG based on alginate and collagen as a cardiac delivery vehicle for EVs. Different concentrations of alginate and collagen crosslinked with calcium gluconate were tested. Based on injectability studies, 1% alginate, 0.5 mg/mL collagen and 0.25% calcium gluconate HG was selected as the idoneous combination for cardiac administration using catheter-based systems. Rheological examination revealed that the HG possessed an internal gel structure, weak mechanical properties and low viscosity, facilitating an easy administration. In addition, EVs were successfully incorporated and homogeneously distributed in the HG. After administration in a rat model of myocardial infarction, the HG showed long-term retention in the heart and allowed for a sustained release of EVs for at least 7 days. Thus, the combination of HGs and EVs represents a promising therapeutic strategy for myocardial repair. Besides EVs delivery, the developed HG could represent a useful platform for cardiac delivery of multiple therapeutic agents.


Building social accountability to improve reproductive, maternal, newborn and child health in Nigeria.
Like many places in Nigeria, Niger, a predominantly rural and poor state in the north of the country, has high fertility, low contraceptive prevalence, and high maternal mortality. This paper presents a descriptive, contextualized case study of a social accountability campaign run by the nongovernmental organization White Ribbon Alliance Nigeria to strategically mobilize collective action to demand quality maternal health care and improve government responsiveness to those demands. We treat maternal health as a component of reproductive health, while recognizing it as a less contested area. Data come from more than 40 interviews with relevant actors in Niger State in 2017 and 2018 during the initial phase of the campaign, and follow-up interviews with White Ribbon Alliance Nigeria staff in 2019 and 2021. Other data include White Ribbon Alliance Nigeria's monthly reports. We analyzed these data both deductively and inductively using qualitative techniques. During its first phase, the campaign used advocacy techniques to convince the previously reticent state government to engage with citizens, and worked to amplify citizen voice by hosting community dialogues and town halls, training a cadre of citizen journalists, and shoring up ward health development committees. Many of these efforts were unsustainable, however, so during the campaign's second phase, White Ribbon Alliance Nigeria worked to solidify state commitment to durable accountability structures intended to survive beyond the campaign's involvement. Key challenges have included a nontransparent state budget release process and the continued need for significant support from White Ribbon Alliance Nigeria. These findings reveal the significant time and resource inputs associated with implementing a strategic social accountability campaign, important compromises around the terminology used to describe "accountability," and the constraints on government responsiveness posed by unrealistic budgeting procedures. The campaign's contributions towards increased social accountability for maternal health should, however, also benefit accountability for reproductive health, as informed and empowered woman are better prepared to demand health services in any sector.


Ablation of atrial fibrillation with minimally invasive mitral surgery.
With the advent of minimally invasive mitral valve surgery, transeptal exposure of the mitral valve has become increasingly popular. While this approach provides excellent exposure of the mitral valve, it necessitates development of novel strategies for concomitant ablation in patients with atrial fibrillation. We describe a technique for creation of a biatrial lesion set for atrial fibrillation ablation that is easily employed using the transeptal approach to the mitral valve.


Human Pluripotent Stem Cells: Myths and Future Realities for Liver Cell Therapy.
The severe shortage of organ donors for treating patients with liver disease has prompted in vitro efforts to produce the main functional cells of the liver: hepatocyte-like cells (Hep cells). We consider the key challenges posed by various stem cell technologies and liver pathologies for developing clinically useful Hep cells.


Space-occupying lesions of the myocardium: role of two-dimensional echocardiography in detection of cardiac tumors in children.
Four patients with space-occupying myocardial lesions were studied using electronically focused high-resolution two-dimensional echocardiography. In two patients with clusters of high-intensity echoes at various depths on the epicardial surface, histology confirmed the diagnosis of lymphosarcoma, showing patchy, malignant infiltrates of different thickness. The remaining two patients had very different features: the lesions appeared to be intrinsic to the posterior left ventricular wall. One patient who had arrhythmias and a small encapsulated noncontractile mass had a histologically proved rhabdomyoma. In the second patient fibroma was histologically confirmed. In these two patients the position of the lesions was confirmed by angiocardiography. Two-dimensional echocardiography greatly improved delineation of space-occupying cardiac masses and is an accurate method for confirming the presence of such lesions.


Tetra-Substituted p-Tert-Butylcalix[4]Arene with Phosphoryl and Salicylamide Functional Groups: Synthesis, Complexation and Selective Extraction of f-Element Cations.
A new series of lanthanide (1-5) and uranyl (6) complexes with a tetra-substituted bifunctional calixarene ligand H2 L is described. The coordination environment for the Ln3+ and UO2 2+ ions is provided by phosphoryl and salicylamide functional groups appended to the lower rim of the p-tert-butylcalix[4]arene scaffold. Ligand interactions with lanthanide cations (light: La3+ , Pr3+ ; intermediate: Eu3+ and Gd3+ ; and heavy: Yb3+ ), as well as the uranyl cation (UO2 2+ ) is examined in the solution and solid state, respectively with spectrophotometric titration and single crystal X-ray diffractometry. The ligand is fully deprotonated in the complexation of trivalent lanthanide ions forming di-cationic complexes 2 : 2 M : L, [Ln2 (L)2 (H2 O)]2+ (1-5), in solution, whereas uranyl formed a 1 : 1 M : L complex [UO2 (L)(MeOH)]∞ (6) that demonstrated very limited solubility in 12 organic solvents. Solvent extraction behaviour is examined for cation selectivity and extraction efficiency. H2 L was found to be an effective extracting agent for UO2 2+ over La3+ and Yb3+ cations. The separation factors at pH 6.0 are: βUO 2 2 + /La 3 + =121.0 and βUO 2 2 + /Yb 3 + =70.0.


Androgen Deprivation Therapy (ADT) Plus Docetaxel Versus ADT Alone in Metastatic Non castrate Prostate Cancer: Impact of Metastatic Burden and Long-term Survival Analysis of the Randomized Phase 3 GETUG-AFU15 Trial.
The role of chemotherapy in metastatic non castrate prostate cancer (mNCPC) is debated. Survival benefits of docetaxel (D) added to androgen-deprivation therapy (ADT) were shown in the CHAARTED trial in patients with metastatic high-volume disease (HVD). To assess the impact of metastatic burden and to update overall survival (OS) data of the GETUG-AFU15 study. Randomized phase 3 trial of ADT plus D versus ADT alone in 385 mNCPC patients; median follow-up of 7 yr. Primary end point was OS. Secondary end points were biochemical progression-free survival (bPFS) and radiographic progression-free survival (rPFS). Retrospective analysis was by tumor volume. After a median follow-up of 83.9 mo, median OS in the overall population was 62.1 mo (95% confidence interval [CI], 49.5-73.7) and 48.6 mo (95% CI, 40.9-60.6) for ADT plus D and ADT arms, respectively (hazard ratio [HR]: 0.88 [95% CI, 0.68-1.14]; p=0.3). Median OS in ADT plus D and ADT arms, respectively, was for HVD patients: 39.8 mo (95% CI, 28.0-53.4) versus 35.1 mo (95% CI, 29.9-43.6) (HR: 0.78 [95% CI, 0.56-1.09]; p=0.14), for low-volume disease (LVD) patients; median was not reached (NR; 95% CI, 69.5-NR) and 83.4 mo (95% CI, 61.8-NR) (HR: 1.02 [95% CI, 0.67-1.55]; p=0.9). For upfront metastatic patients, OS was 52.6 mo (95% CI, 43.3-66.8) and 41.5 mo (95% CI, 36.3-54.5), respectively (HR: 0.93 [95% CI, 0.69-1.25]; p=0.6). The bPFS (HR: 0.73 [95% CI, 0.56-0.94]; p=0.014) and rPFS (HR: 0.75 [95% CI, 0.58-0.97]; p=0.030) were significantly longer in the ADT plus D arm. Limitations included the retrospective analysis of metastatic extent and the lack of statistical power to detect a significant difference in subgroups. The post hoc analyses of the GETUG-AFU15 study demonstrated a nonsignificant 20% reduction in the risk of death in the HVD subgroup. Patients with LVD had no survival improvement with early D. In this study, docetaxel added to castration did not improve survival in patients with metastatic hormone-sensitive prostate cancer, partly due to methodological issues. However, early chemotherapy should be discussed with all patients, given the data of three randomized trials including GETUG-AFU15.


Second mesiobuccal root canal in maxillary molars-A systematic review and meta-analysis of prevalence studies using cone beam computed tomography.
To assess the influence of cone-beam computed tomographic (CBCT) voxel size and population demographic aspects (age, gender and geographic region) on the prevalence of the second mesiobuccal root canal (MB2) in maxillary first and second molars. Prevalence studies using CBCT technology on MB2 canal were searched between May and September 2019. The protocol was registered in PROSPERO. Four electronic databases and 5 peer-reviewed endodontic journals were screened. Authors were contacted and bibliographic references hand-searched. Eighty three studies were submitted to full text analysis and scientific merit evaluation by 2 evaluators using Joanna Briggs Institute Critical Appraisal tool. Twenty six studies were finally pooled into a meta-analysis. Forest plots with a 95% confidence interval were undertaken. Meta-regression was used to identify possible sources of heterogeneity and funnel plot visual analysis to assess publication bias. The 26 studies reported anatomical data from the mesiobuccal root of 15,285 first molars and 8,641 second molars. Pooled prevalence of MB2 canal was higher in maxillary first molar (69.6%; 64.5%-74.8%) than in second molars (39.0%; 31.1%-46.9%) (p < 0.05). A significantly higher prevalence odds of having MB2 canal was detected in males (p < 0.05). Meta-regression excluded gender, age and voxel size as a source variance, but identified tooth group and geographic region as possible sources of heterogeneity. MB2 canal prevalence was significantly higher in maxillary first molars. Males showed higher odds of having MB2 canal than females. Geographic region seemed to influence MB2 prevalence outcome. Knowing these preoperative factors would help to anticipate MB2 morphologies in clinics.


Autoimmunity in lichen planopilaris patients.
Lichen planopilaris (LPP) is a rare, scarring form of alopecia with lymphocytic pattern. Due to the destruction of epithelial hair follicle stem cells in the bulge, it represents an irreversible condition. Antinuclear antibodies have been used for decades as diagnostic biomarkers of several rheumatological diseases. The aim of study was to determine the frequency of anti-nuclear antibodies positivity and subsequently analyze the presence of specific antibodies in LPP patients. 57 patients (aged 28-79, female 96%) were included in the study. Patients with LPP were treated in Department of Dermatology of University Hospital in Cracow, Poland and were identified on individual record review. Antinuclear antibodies were detected using indirect immunofluorescence on HEp-2 cells and immunoblot test. Antinuclear antibodies were detected in sera of 48 out of 57 LPP patients (84,2%). In 22 (46%) patients antinuclear antibodies specificity could be defined, anti-dsDNA and anti-Ro/anti-SSA being most common. Antinuclear antibodies were detected in sera of 48 out of 57 LPP patients (84,2%). In 22 (46%) patients antinuclear antibodies specificity could be defined, anti-dsDNA and anti-Ro/anti-SSA being most common.


Axonal-transsynaptic spread as the basic pathogenetic mechanism in B virus infection of the nervous system.
An experimental study on the pathogenesis of B virus infection in the mouse has documented that the agent spreads in an axonal-transsynaptic manner in the nervous system. The characteristics of the spread of B virus are similar to those of other members of the herpes virus group.


Development of stably transfected monolayer overexpressing the human apical sodium-dependent bile acid transporter (hASBT).
The human apical sodium-dependent bile acid transporter (hASBT) represents a potential target for prodrug design to increase oral drug absorption. Unfortunately, available monolayer cell culture models do not reliably express hASBT, and nonpolarized cells only allow for uptake assessment, which limits prodrug development efforts. The objective of this study was to develop and characterize a stably transfected hASBT-MDCK cell line. cDNA encoding hASBT was cloned into pcDNA3.1-V5-polyHis-B to generate an expression plasmid that was then transfected into MDCK-II cells. Clonal populations were chosen based on high hASBT activity and monolayer integrity. Western blot confirmed the expression of the recombinant hASBT; functionality was characterized using taurocholic acid. In the selected clone, hASBT-mediated taurocholate permeability across hASBT-MDCK monolayers was almost 25-fold higher with sodium, than without sodium where hASBT is not functional. In the presence of sodium, taurocholate and mannitol permeabilities were 23.0x10(-6) cm/sec and 2.60x10(-6) cm/s, respectively, indicating high hASBT functionality and monolayer integrity. hASBT-MDCK monolayer properties were stable over 6 months and demonstrated low within-day variability. Taurocholate uptake and inhibition kinetic parameters from hASBT-MDCK were similar to those obtained from hASBT-COS7 model, confirming hASBT functionality in hASBT-MDCK. Results indicate that the developed hASBT-MDCK system is a competent, high-expression, stable assay for hASBT transport and inhibition studies.


Proteomic analysis of stress-related proteins and metabolic pathways in Picea asperata somatic embryos during partial desiccation.
Partial desiccation treatment (PDT) stimulates germination and enhances the conversion of conifer somatic embryos. To better understand the mechanisms underlying the responses of somatic embryos to PDT, we used proteomic and physiological analyses to investigate these responses during PDT in Picea asperata. Comparative proteomic analysis revealed that, during PDT, stress-related proteins were mainly involved in osmosis, endogenous hormones, antioxidative proteins, molecular chaperones and defence-related proteins. Compared with those in cotyledonary embryos before PDT, these stress-related proteins remained at high levels on days 7 (D7) and 14 (D14) of PDT. The proteins that differentially accumulated in the somatic embryos on D7 were mapped to stress and/or stimuli. They may also be involved in the glyoxylate cycle and the chitin metabolic process. The most significant difference in the differentially accumulated proteins occurred in the metabolic pathways of photosynthesis on D14. Furthermore, in accordance with the changes in stress-related proteins, analyses of changes in water content, abscisic acid, indoleacetic acid and H2 O2 levels in the embryos indicated that PDT is involved in water-deficit tolerance and affects endogenous hormones. Our results provide insight into the mechanisms responsible for the transition from morphologically mature to physiologically mature somatic embryos during the PDT process in P. asperata.


Do tanning salons adhere to new legal regulations? Results of a simulated client trial in Germany.
In August 2009 and January 2012, two regulations were passed in Germany to limit UV exposure in the general population. These regulations state that no minors are allowed to use tanning devices. Personnel of tanning salons is mandated to offer counseling regarding individual skin type, to create a dosage plan with the customer and to provide a list describing harmful effects of UV radiation. Furthermore, a poster of warning criteria has to be visible and readable at all times inside the tanning salon. It is unclear whether these regulations are followed by employees of tanning salons in Germany, and we are not aware of any studies examining the implementation of the regulations at individual salons. We performed a simulated client study visiting 20 tanning salons in the city-state of Bremen in the year 2014, using a short checklist of criteria derived from the legal requirements, to evaluate whether legal requirements were followed or not. We found that only 20 % of the tanning salons communicated adverse health effects of UV radiation in visible posters and other materials and that only 60 % of the salons offered the required determination of the skin type to customers. In addition, only 60 % of the salons offered to complete the required dosage plan with their customers. To conclude, our results suggest that the new regulations are insufficiently implemented in Bremen. Additional control mechanisms appear necessary to ensure that consumers are protected from possible carcinogenic effects of excessive UV radiation.


CD4(+) T-lymphocytes regulate airway remodeling and hyper-reactivity in a mouse model of chronic asthma.
Asthma is an acute-on-chronic inflammatory disease of the airways, characterized by airflow obstruction and hyper-reactivity of the airways to a variety of stimuli. Chronic asthma is associated with remodeling of the airway wall, which may contribute to hyper-reactivity and fixed airflow obstruction. We used an improved mouse model of chronic asthma to investigate the role of CD4(+) T-lymphocytes in airway remodeling and hyper-reactivity. Animals functionally depleted of CD4(+) T-lymphocytes by repeated administration of a monoclonal antibody exhibited markedly decreased airway responsiveness. In addition, these mice had greatly diminished subepithelial fibrosis, epithelial thickening, and mucous cell hyperplasia/metaplasia. Chronic inflammation in the airway wall was moderately reduced, with a marked decrease in the accumulation of immunoglobulin-synthesizing plasma cells. However, intraepithelial accumulation of eosinophils was not significantly inhibited and airway epithelial expression of eotaxin was undiminished. This work provides the first experimental evidence that CD4(+) T-lymphocytes play a crucial role in the pathogenesis of the lesions of chronic asthma and lends support to the notion that functional inhibition of these cells may be an important therapeutic target.


Semi-Continuity of Skeletons in Two-Manifold and Discrete Voronoi Approximation.
The skeleton of a 2D shape is an important geometric structure in pattern analysis and computer vision. In this paper we study the skeleton of a 2D shape in a two-manifold M , based on a geodesic metric. We present a formal definition of the skeleton S(Ω) for a shape Ω in M and show several properties that make S(Ω) distinct from its Euclidean counterpart in R(2). We further prove that for a shape sequence {Ωi} that converge to a shape Ω in M, the mapping Ω→ S̅(Ω) is lower semi-continuous. A direct application of this result is that we can use a set P of sample points to approximate the boundary of a 2D shape Ω, and the Voronoi diagram of P inside Ω ⊂ M gives a good approximation to the skeleton S(Ω) . Examples of skeleton computation in topography and brain morphometry are illustrated.


Management of obstructive sleep apnea syndrome type 1 in children and adolescents - A French consensus.
This document is the outcome of a group of experts brought together at the request of the French Society of Sleep Research and Medicine to provide recommendations for the management of obstructive sleep apnea syndrome type 1 (OSA1) in children. The recommendations are based on shared experience and published literature. OSA1 is suspected when several nighttime respiratory symptoms related to upper airway obstruction are identified on clinical history taking. A specialist otolaryngologist examination, including nasofibroscopy, is essential during diagnosis. A sleep study for OSA1 is not mandatory when at least two nighttime symptoms (including snoring) are noted. Therapeutic management must be individualized according to the location of the obstruction. Ear, nose, and throat (ENT) surgery is often required, as hypertrophy of the lymphoid tissues is the main cause of OSA1 in children. According to clinical findings, orthodontic treatment generally associated with specialized orofacial-myofunctional therapy might also be indicated. Whatever treatment is chosen, follow-up must be continuous and multidisciplinary, in a network of trained specialists.


Effectiveness of fibrin glue in skin graft survival: A systematic review and meta-analysis.
The objective of this study is to assess the current literature on the effectiveness of fibrin glue on survival of skin grafts. Fibrin glue is a possible alternative to secure skin grafts instead of traditional methods (i.e. sutures or staples). Data Sources: MEDLINE, Scopus, Embase, Informit, CINAHL and the Cochrane Central Register of Controlled Trials, no limit on the earliest date of publication. Randomised, non-randomised controlled trials and cohort studies. and Interventions: Participants were patients with skin grafting/skin transplantation. The intervention was fibrin glue in any form (bovine, human pooled plasma or autologous) and comparator any form of affixing skin grafts (e.g. sutures or staples).Study Appraisal and Synthesis Methods: Studies were appraised using the Cochrane risk of bias tool and assessed for clinical heterogeneity. Effect sizes were calculated and illustrated with forest plots. 190 publications were narrowed to 15 relevant publications, of which eight were pooled in meta-analysis. The outcomes examined were: graft survival by percentage; graft survival reported as events; post-operative incidence of haematoma or seroma; pain reported after dressing changes via a visual analogue scale; length of stay in days (Glass's delta 2 was 0.48 95% CI 0.09, 0.97); and surgical time in minutes. Only length of stay showed a difference between groups and it favoured fibrin glue. While there may be benefits to the use of fibrin glue in skin graft patients, it is difficult to conclude this from the current evidence. Limitations were significant heterogeneity in outcomes measured and exclusion off non-English papers.


Measuring ambulation in adults with central neurologic disorders.
This review discusses challenges faced by clinicians and researchers when measuring ambulation in individuals with central neurologic disorders within 3 distinct environments: clinical, laboratory, and community. Even the most robust measure of ambulation is affected by the environment in which it is implemented and by the clinical or research question and the specificity of the hypothesis being investigated. The ability to accurately measure ambulation (one of the most important metrics used to show transition into a community environment) is essential to measure treatment effectiveness and rehabilitation outcomes in populations with central neurologic disorders.


The significance of cerebral infarction and atrophy in patients with amaurosis fugax and transient ischemic attacks in relation to internal carotid artery stenosis: a preliminary report.
There is a growing appreciation for the high incidence of silent cerebral infarction and cerebral atrophy on CT scans in patients with amaurosis fugax (AF) and hemispheric transient ischemic attacks (TIAs). Seventy patients with AF only (no TIAs), 104 patients with hemispheric TIAs (no AF), 185 patients without focal carotid territory symptoms (i.e., vertebrobasilar TIAs or asymptomatic carotid bruit only), and 129 patients with stroke and good recovery were studied with CT scan and duplex scanning to grade the degree of stenosis of the internal carotid artery (grades: A = normal, B = 0% to 15% stenosis, C = 16% to 49%, D = 50% to 99%, and E = occlusion). In patients with AF, the incidence of infarction increased from 20% in grades A, B, and C to 40% in grade D and 58% in grade E. The incidence of atrophy increased in parallel from 10% in grade A to 30% in grade E. The increased incidence of atrophy with increasing degrees of stenosis was not the result of increasing degrees of stenosis per se, but the associated increase in the incidence of infarction (patients without CT infarcts in grades D and E had 5% and 0% incidence of atrophy). In patients with hemispheric TIAs, the incidence of CT infarction increased from 25% in grades A and B to 48% in grades D and E. The incidence of atrophy did not show a parallel increase. Our findings support the hypothesis that atrophy is associated not only with cerebral infarction but may be causally related.(ABSTRACT TRUNCATED AT 250 WORDS)


The impact of chloride and chlorine radical on nitrite formation during vacuum UV photolysis of water.
The impact of chloride ion and chlorine radical on the formation of nitrite was investigated under Vacuum-UV (VUV) photolysis of nitrate contaminating water. An increase in chloride concentration reduced nitrite formation in part due to the relatively high VUV absorption of chloride. The use of various radical scavengers, such as acetate and acetone, helped delineate the specific roles of hydroxyl radical (HO) and chlorine radical (Cl) in oxidation and VUV photolysis of nitrate, and the subsequent formation of nitrite. HO reduced nitrite formation due to its high reaction rate constant with nitrite. Nitrite formation in both chloride and dissolved organic carbon (DOC) containing solution depended primarily on their relative concentrations. Carbamazepine (CBZ) was also used to analyze the effect of Cl on both the degradation of CBZ and the formation of nitrite. Cl showed to significantly increase the degradation of CBZ, but it had little impact on the formation of nitrite. This paper, utilizing detailed experimental data combined with kinetic modeling and mechanistic analysis of VUV photolysis in the presence of chloride and nitrate, provides the necessary scientific guidance towards more effective and optimized applications of VUV technology for drinking water treatment.


Parenteral Nutrition.
Prematurity and other complications at birth are nutritional emergencies. Parenteral nutrition is a bridge to enteral nutrition for a few days or months, and sometimes the sole source of nutrition for life. Parenteral nutrition regimens are constructed to provide adequate and balanced energy, macronutrients, and micronutrients to support growth and prevent deficiencies. Neonatal parenteral nutrition regimens are complicated by periodic shortages of essential products, compatibility challenges, and contaminants. Newborns benefit from serial growth assessments, monitoring of biochemical status, nutrition-focused physical examinations, and management by a multidisciplinary team to ensure adequacy of parenteral nutrition and promote best outcomes.


Characterizing Pain Leading to Emergency Medical Services Activation in Heart Failure.
Pain is a common but understudied symptom among patients with heart failure (HF) transported by emergency medical services (EMS). The aims were to determine explanatory factors of a primary complaint of pain and pain severity, and characterize pain among patients with HF transported by EMS. Data from electronic health records of patients with HF transported by EMS within a midwestern United States county from 2009 to 2017 were analyzed. Descriptive statistics, χ 2 , analysis of variance, and logistic and multiple linear regression analyses were used. The sample (N = 4663) was predominantly women (58.1%) with self-reported race as Black (57.7%). The mean age was 64.2 ± 14.3 years. Pain was the primary complaint in 22.2% of the sample, with an average pain score of 6.8 ± 3.1 out of 10. The most common pain complaint was chest pain (68.1%). Factors associated with a primary pain complaint were younger age (odds ratio [OR], 0.97; 95% confidence interval [CI], 0.96-0.97), history of myocardial infarction (OR, 1.96; 95% CI, 1.55-2.49), and absence of shortness of breath (OR, 0.67; 95% CI, 0.58-0.77). Factors associated with higher pain severity were younger age ( b = -0.05, SE = 0.013), being a woman ( b = 1.17, SE = 0.357), and White race ( b = -1.11, SE = 0.349). Clinical and demographic factors need consideration in understanding pain in HF during EMS transport. Additional research is needed to examine these factors to improve pain management and reduce transports due to pain.


Imaging of primary rhabdomyosarcoma of the diaphragm.
This is a report on a rare case of embryonal rhabdomyosarcoma involving the diaphragm in a 3-year-old boy. This case illustrates the importance of preoperative imaging in the management of this tumor.


Percutaneous fixation and balloon kyphoplasty for the treatment of A3 thoracolumbar fractures.
Despite a long history of descriptive and clinical series, there is still no consensus in the treatment of traumatic thoracolumbar fractures. It is now widely accepted that percutaneous surgery in thoracolumbar spine trauma management can achieve the same results as conventional treatment but less morbidity but it is still not clear which are the best indications for these minimal invasive procedures. Thirty-two adult patients with single type A3 thoracolumbar burst fractures without neurologic deficits were included in this retrospective review of clinical and radiological outcomes after surgical management. All patients underwent combined percutaneous kyphoplasty and short fixation with screws in the vertebral pedicles above and below the fracture. Radiographic evaluation of segmental kyphosis and local kyphotic corrections were made preoperatively, 3 days postoperatively, 12 months post-operatively and at the last follow-up (the mean last follow-up was 41 months post-operatively). Clinical outcomes were determined by SF-36® Health Survey and Oswestry Disability Index scores at 3-month and 12-month follow-ups. Clinical assessments suggested good outcomes as early as the third postoperative month. The clinical outcomes were sustained at one year follow-up. At the last follow-up the segmental kyphosis correction and local kyphotic correction were maintained. Our analysis demonstrates that minimally invasive kyphoplasty and percutaneous short fixation applied to thoracolumbar A3 burst fractures without neurological deficit may achieve results comparable to nonsurgical or open surgical treatment, but with less morbidity and complication, and should be considered as a valid treatment option.


Associations between resting state functional brain connectivity and childhood anhedonia: A reproduction and replication study.
Previously, a study using a sample of the Adolescent Brain Cognitive Development (ABCD)® study from the earlier 1.0 release found differences in several resting state functional MRI (rsfMRI) brain connectivity measures associated with children reporting anhedonia. Here, we aim to reproduce, replicate, and extend the previous findings using data from the later ABCD study 4.0 release, which includes a significantly larger sample. To reproduce and replicate the previous authors' findings, we analyzed data from the ABCD 1.0 release (n = 2437), from an independent subsample from the newer ABCD 4.0 release (excluding individuals from the 1.0 release) (n = 6456), and from the full ABCD 4.0 release sample (n = 8866). Additionally, we assessed whether using a multiple linear regression approach could improve replicability by controlling for the effects of comorbid psychiatric conditions and sociodemographic covariates. While the previously reported associations were reproducible, effect sizes for most rsfMRI measures were drastically reduced in replication analyses (including for both t-tests and multiple linear regressions) using the ABCD 4.0 (excluding 1.0) sample. However, 2 new rsfMRI measures (the Auditory vs. Right Putamen and the Retrosplenial-Temporal vs. Right-Thalamus-Proper measures) exhibited replicable associations with anhedonia and stable, albeit small, effect sizes across the ABCD samples, even after accounting for sociodemographic covariates and comorbid psychiatric conditions using a multiple linear regression approach. The most statistically significant associations between anhedonia and rsfMRI connectivity measures found in the ABCD 1.0 sample tended to be non-replicable and inflated. Contrastingly, replicable associations exhibited smaller effects with less statistical significance in the ABCD 1.0 sample. Multiple linear regressions helped assess the specificity of these findings and control the effects of confounding covariates.


Rapid fluorometric test for the quantitative determination of deoxynivalenol in raw cereals.
Fast test systems fulfilling legislative specifications are required to determine mycotoxin contamination in unprocessed cerealse.g. at grain elevators, import and export terminals, or the milling and brewing industry to prevent contamination of food and feed.We describe the first tests of a novel fluorescence-based test for deoxynivalenol (DON), which will be commercially available within the next few months.The analytical procedure of the new test takes less than 15 minutes for extraction, purification, derivatization and measurement. The system's advantage is its speed and easy procedure providing quantitative DON determination.To ensure an international standard, the validation procedure for wheat, barley and maize will be performed following USDA/GIPSA requirements (03/2006) for DON tests.


A cross-national cross-sectional survey of the attitudes and perceived competence of final-year medicine, nursing and pharmacy students in relation to end-of-life care in dementia.
Little is known about the attitudes of healthcare professional students' perceived competence and confidence in treating those with dementia who are at the end of life. To explore the attitudes of final year medical, nursing and pharmacy students towards people with dementia and to evaluate their perceived competence and confidence dealing with biomedical and psychosocial issues within the context of palliative care provision to patients with dementia. Cross-sectional survey using a questionnaire. Final-year students in each profession from Queen's University Belfast (Northern Ireland) and the University of Iowa (USA) were recruited. Three versions of an online questionnaire (containing the Attitudes to Dementia Questionnaire and a series of questions on end-of-life care in dementia) were distributed. A total of 368 responses were received (response rate 42.3%). All respondents reported positive attitudes towards people with dementia. US nursing students reported significantly more positive attitudes than the medical students of United States and Northern Ireland. Medical students were more likely to report low confidence in discussing non-medical aspects of dying, whereas nursing students were most likely to feel prepared and confident to do this. Medical and nursing students reported low confidence with aspects of medication-related care; however, data from the pharmacy samples of Northern Ireland and United States suggested that these students felt confident in advising other healthcare professionals on medication-related issues. While healthcare students hold positive attitudes towards people with dementia, some clinical tasks remain challenging and further basic training may be of benefit.


Compliance with an ordinance requiring the use of personal flotation devices by children in public waterways.
For children ages 1-14, 21.6% of drowning cases involve swimming, wading, or playing in natural bodies of water, such as rivers and lakes. Personal flotation devices (PFDs) are believed to be an effective prevention measure. We measure compliance with city and county ordinances, publicized but not actively enforced, requiring that PFDs be worn by children accessing public bodies of water in Sacramento County, California. During June-August 2010, volunteers conducted 79 observation sessions at three popular local river beaches where PFDs were available for use at no cost. They recorded personal characteristics and PFD use for 1,727 children in or very near the water and believed to be 0-13 years of age (the age covered by the ordinances). We used logistic regression to quantify differences in use by subject characteristics and study site. The prevalence of PFD use was 29.9% overall, with large and significant differences by age: < 1, 55.6%; 1-4, 37.6%; 5-10, 29.4%; 10-13, 14.6%; P < 0.0001. Usage did not vary significantly by sex or race/ethnicity, and was somewhat higher at one study site (33.1%) than at the others (25.9% and 27.3%), P = 0.009. The combination of a statutory requirement and a cost-elimination strategy was associated with moderate rates of PFD use that were highest among young children.


Motor variability: within-subject correlations during separate and simultaneous contractions.
To determine the similarity of motor variability in proximal muscles, young and elderly adults performed steady elbow flexor (EF) and knee extensor (KE) contractions separately (SEP; at 2.5, 30, and 65% of maximum) and simultaneously (SIM; at 2.5 and 30% of maximum), with (VIS) and without (NVIS) visual feedback. Between-muscle correlations of fluctuation amplitude (SD, CV of force), time-based cross-correlations (CC), force power spectra, and frequency-based coherence (COH) values were computed from the concurrent force records. Correlations of fluctuation amplitude ranged from r = 0.34 to 0.86 (P < 0.05) across forces, SEP/SIM, and vision conditions, but were absent for 2.5% NVIS. The relatively low CC values for SIM (r = 0.22-0.33) were stronger for elderly than young adults. The vast majority of the power in the force fluctuations was <4 Hz for all records. Weak COH peaks were only observed <2 Hz for elderly and between 3 and 4 Hz for young, and COH was slightly stronger for elderly below 3 Hz for the 30% MVC target force. The correlations in force fluctuation amplitude suggest that the EF and KE motor neuron pools similarly transform the oscillating synaptic input and may influence each other. The cross-correlations suggest the remote motor neuron pools are influenced similarly in time by a common source of excitation, perhaps more coherently for elderly adults at low frequencies.


Changes in expression of the CD200 tolerance-signaling molecule and its receptor (CD200R) by villus trophoblasts during first trimester missed abortion and in chronic histiocytic intervillositis.
Expression of CD200 at the feto-maternal interface is associated with successful murine and human pregnancy. CD200 binding to CD200 receptors on lymphomyeloid cells suppresses inflammation and induces Tregs. CD200 receptors are also expressed on mouse and human placental trophoblast cells. What is the expression of CD200 and CD200R in human missed abortions which have preserved Treg levels and in chronic histiocytic intervillositis (CHI) where maternal inflammatory cells cause IUGR? Immunohistiochemistry for CD200, CD200R, and Ki67 using human placental sections from missed abortions, term placenta, and CHI. PCR testing was done for trisomy in missed abortion. CD200 and CD200R were expressed by human villus trophoblasts from 2 weeks post-implantation to term. Cytotrophoblast proliferation (Ki-67+ count) decreased at term. In first trimester missed abortion cases, CD200>CD200R villus trophoblasts accompanied missed abortion of non-trisomic male fetuses. CD200 and Ki67+ trophoblast proliferation was preserved in CHI with maternal inflammatory cell infiltration but CD200R was greatly decreased. Residual CD200 activity may prevent completion of abortions via induction of Treg cells. In CHI, infiltrating maternal effector T cells may block Treg induction. An autocrine role for CD200-CD200R interaction versus inhibition of soluble CD200 by soluble CD200R is discussed.


Application of Multi-Perspectives in Tea Breeding and the Main Directions.
Tea plants are an economically important crop and conducting research on tea breeding contributes to enhancing the yield and quality of tea leaves as well as breeding traits that satisfy the requirements of the public. This study reviews the current status of tea plants germplasm resources and their utilization, which has provided genetic material for the application of multi-omics, including genomics and transcriptomics in breeding. Various molecular markers for breeding were designed based on multi-omics, and available approaches in the direction of high yield, quality and resistance in tea plants breeding are proposed. Additionally, future breeding of tea plants based on single-cellomics, pangenomics, plant-microbe interactions and epigenetics are proposed and provided as references. This study aims to provide inspiration and guidance for advancing the development of genetic breeding in tea plants, as well as providing implications for breeding research in other crops.


Modeling spatial, developmental, physiological, and topological constraints on human brain connectivity.
The complex connectivity of nervous systems is thought to have been shaped by competitive selection pressures to minimize wiring costs and support adaptive function. Accordingly, recent modeling work indicates that stochastic processes, shaped by putative trade-offs between the cost and value of each connection, can successfully reproduce many topological properties of macroscale human connectomes measured with diffusion magnetic resonance imaging. Here, we derive a new formalism that more accurately captures the competing pressures of wiring cost minimization and topological complexity. We further show that model performance can be improved by accounting for developmental changes in brain geometry and associated wiring costs, and by using interregional transcriptional or microstructural similarity rather than topological wiring rules. However, all models struggled to capture topographical (i.e., spatial) network properties. Our findings highlight an important role for genetics in shaping macroscale brain connectivity and indicate that stochastic models offer an incomplete account of connectome organization.


Obtainment of lignocellulose degradation microbial community: the effect of acid-base combination after restrictive enrichment.
Microbial communities for bioconversion of lignocellulose have received widespread attention. Many cellulose-degrading microbial communities have been enriched from different sources. Combining two microbial communities with acidic and basic properties (acid-base combination) is a technique used alongside restricted enrichment culturing. Understanding how changes to microbial communities result in community's structure and function is important for mechanistic reconstruction of microbiomes. In this study, we analyzed changes in microbial community structure to elucidate determination of the mechanisms of acid-base combination. We found that after restricted enrichment, the bacteria that were primarily retaining included not only those that decompose and utilize lignocellulose, such as Clostridium and Pseudomonas, but also synergistic microbiota such as Alkalobacillaceae. When the proportion of these two types of bacteria was unbalanced, the degradative ability of the microbial community was low, or pH changes of it did not compound regular changes, which may lead to the failure of restricted enrichment. Microbial communities were re-constituted by acid-base combination, whereby the degrading and synergistic strains were adjusted to a more appropriate proportion. The acid-base combination fixed the instability of microbial communities caused by the randomness of restrictive screening enrichment; it provided an effective method for obtaining high-quality lignocellulose-degrading microbial community.


Kinetic properties of electrostatic pores with orientable dipoles, for Na+ and K+ transport through biological membranes.
The model, used previously to account for the transport of K+ ions through squid axon membranes under steady-state conditions, is extended to the description of the kinetic behavior of Na+ and K+ currents, for sudden variations of the applied potential. Theoretical curves are obtained by numerical integration of the electrodiffusion equation for ions within pores, with variable boundary conditions resulting from a progressive reorientation of dipoles at the pore surface. The pores are supposed to be selective and the dipole parameters are allowed to be different for Na+ and K+ pores. The K+ current varies with time, in agreement with the K+ dipole parameters deduced from the steady-state results of Gilbert and Ehrenstein (1969). The dipole parameters for Na+ current are deduced from the steady-state results of Armstrong, Bezanilla & Rojas (1973), where the inactivation phase of the Na+ current is suppressed by introducing pronase in the inside solution. The dipole reorientation is relavent to explain the sigmoid shape of the activation phase of the Na+ current, while the inactivation phase seems to resort to another physical mechanism. The predictions based on this model agree with the experimental results for the steady-state negative resistance and the gating current, associated both with a reorientation of surface dipoles, as well as the activation phase of the Na+ current using a consistent set of parameters for all these comparisons.


Eosinophilia in premature infants: relationship to weight gain.
Serial eosinophil counts were determined in 38 hospitalized, appropriately grown premature infants whose gestational ages ranged from 27 to 35 weeks. Absolute eosinophilia (greater than 700/mm3) was documented in 76% (29/38). Eosinophilia was mild (700 to 999/mm3) in 9, moderate (1,000 to 2,999/mm3) in 17, and marked (greater than or equal to 3,000/mm3) in 3 patients. The average time of onset was day 19. Peak eosinophilia was usually seen within one week of onset and lasted an average of 16 days. A consistent relationship (r = 0.86) was found between the day of peak eosinophilia (mean = day 27) and the day on which birthweight was regained (mean = day 22). No association was apparent between the occurrence or degree of eosinophilia and gestational age, birth stress, presence of umbilical catheter, parenteral alimentation solution, and time of beginning or type or oral feeds. The data suggest that eosinophilia is strongly associated with the establishment of an anabolic state.


Moralizing gods revisited.
Six ideas explaining the existence of moralizing gods are mentioned, and I discuss the words prosocial and antisocial.


Giant cell tumor of the skull: a case report and review of the literature.
Giant cell tumors are benign lesions that typically occur at the epiphyses of long bones that typically present with pain or swelling. Most data on giant cell tumors in the skull consist of case reports, and many large series of giant cell tumors have no examples in the skull. We report a case of giant cell tumor of the skull and review the literature on these lesions. A 24-year-old woman presented with localized tenderness and mild swelling over the left inferior parietal and occipital bones. She was neurologically intact with a nonmobile, tender, palpable mass over the left subocciptal area. A computed tomography (CT) scan showed a radiolucent, expansile, lytic lesion involving the left occipital bone. The patient underwent a left occipital craniectomy with resection of the bone and epidural mass. Permanent histopathologic sections and immunostains revealed a giant cell tumor. Giant cell tumors are generally benign, locally aggressive lesions for which surgical excision is the treatment of choice. This report contributes to the scarce literature on these tumors in the skull.


Candida yeast long chain fatty alcohol oxidase is a c-type haemoprotein and plays an important role in long chain fatty acid metabolism.
The industrial yeasts Candida tropicalis or Candida cloacae are able to grow on a variety of long chain alkanes and fatty acids as the sole carbon source. The complete oxidation of these substrates involves two sequential oxidative pathways: omega-oxidation, comprising the P450 alkane oxidase, a flavin-dependent membrane-bound long chain fatty alcohol oxidase [FAO] and a possible separate aldehyde oxidase [F.M. Dickinson, C. Wadforth, Purification and some properties of alcohol oxidase from alkane-grown Candida tropicalis, Biochem. J. 282 (1992) 325-331], and the beta-oxidation pathway, which utilises acylCoA substrates. We recently purified the membrane-bound long chain fatty alcohol oxidase FAO1 and confirmed it is also a c-type haemoprotein. Multiple isoforms may exist for many of these long chain fatty alcohol oxidases and the in vivo requirements for individual genes with respect to specific substrates are still being elucidated. In vitro reconstitution experiments have demonstrated that in Candida maltosa, the cytochrome P450 52A3 gene product can completely oxidise alkanes to dicarboxylic acids [U. Scheller, T. Zimmer, D. Becher, F. Schauer, W. Schunck, Oxygenation Cascade in Conversion of n-Alkanes to, -Dioic Acids Catalyzed by Cytochrome P450 52A3, J. Biol. Chem. 273 (1998) 32528-32534], potentially obviating requirements for a long chain alcohol oxidase. Here, we directly determine in vivo the role of the long chain alcohol oxidase (FAOT) in C. tropicalis, grown on a variety of substrates, followed by gene deletion. The faot double knockout has no detectable faot activity and is incapable of growth on octadecane, but it grows well on oleic acid, palmitic acid and shorter chain alkanes/fatty acids. A spontaneous mutation[s] may have occurred in the faot double gene knockout of C. tropicalis resulting in its inability to grow on oleic acid and hexadecane. The mutations demonstrate that different pathways of octadecane, hexadecane, oleic acid and palmitic acid utilisation exist in C. tropicalis.


Clinical profile and microbiological aetiology diagnosis in adult patients hospitalized with community-acquired pneumonia.
Early introduction of appropriate antibiotherapy is one of the major prognostic-modifying factors in community acquired pneumonia (CAP). Despite established guidelines for empirical therapy, several factors may influence etiology and, consequently, antibiotic choices. The aims of this study were to analyze the etiology of CAP in adults admitted to a northern Portugal University Hospital and evaluate the yield of the different methods used to reach an etiological diagnosis, as well as analyze of the impact of patient demographic and clinical features on CAP etiology. We retrospectively analyzed 1901 cases of CAP with hospitalization. The diagnostic performance increased significantly when blood and sputum cultures were combined with urinary antigen tests. The most frequent etiological agent was Streptococcus pneumoniae (45.7%), except in August, when it was overtaken by gram-negative bacilli (GNB) and Legionella pneumophila infections. Viral infections were almost exclusive to winter and spring. A negative microbiological result was associated with increasing age, non-smoking and lack of both blood/sputum cultures. Younger age was a predictor for S. pneumoniae, Influenza and L. pneumophila infections. Active smoking without any previously known respiratory disease was a risk factor for legionellosis. COPD was associated with Haemophilus influenzae cases, while dementia was typical in GNB and S. aureus patients. Diabetes mellitus (DM) and heart disease were negative predictors of S. pneumoniae and H. influenzae, respectively. P. aeruginosa was an independent risk factor for mortality (OR 13.02, 95% CI 2.94-57.7). This study highlights the importance of a comprehensive microbiological diagnostic workup and provides clues to predicting the most probable CAP causative agents, based on a patient's clinical profile. These may be taken into account when establishing first line antibiotherapy.


Further report of a prospective randomized trial comparing distal splenorenal shunt with end-to-side portacaval shunt. An analysis of encephalopathy, survival, and quality of life.
We electively compared the distal splenorenal ("selective") shunt with the end-to-side portacaval shunt in 80 prospectively randomized patients with variceal bleeding. Selective shunts required more operative time (3.9 vs. 2.8 h) and blood replacement (4.6 vs. 2.5 U) and postoperative mortality was slightly higher (5 of 38 selective vs. 0 of 40 portacaval). Postoperative complication rates were similar. After 65-mo mean follow-up, both shunts have protected well against late gastrointestinal bleeding (5 selective, 4 portacaval episodes). However, after selective shunts, spontaneous encephalopathy occurred less often (23% vs. 40% of patients), was severe in fewer patients (12% vs. 33%), and precipitated fewer hospital admissions (6 admissions in 4 selective patients vs. 26 admissions in 13 portacaval patients). Furthermore, selective shunt patients remained longer without functional disability (83% vs. 70% of postoperative patient months). Long-term survival was not significantly different in the two groups (5-yr survival: selective 51%, portacaval 56%).


A simple, nonenzymatic method for desialylating polysialylated ganglio-N-tetraose series gangliosides to produce GM1.
Dowex-50W-H+ was used to catalyze the highly selective desialylation of polysialylated ganglio-N-tetraose series gangliosides to yield primarily GM1. High performance thin-layer chromatographic analysis of recovered lipid indicated that 60-70% of the recovered ganglioside was GM1. Identification of the major product as GM1 was confirmed by proton NMR spectra and lack of sialic acid release by Vibrio cholerae sialidase.


Right and left ventricular cardiac function in a developed world population with human immunodeficiency virus studied with radionuclide ventriculography.
Cardiac dysfunction has been reported in a substantial part of patients infected with the human immunodeficiency virus (HIV). However, most studies are from a time before the introduction of highly active antiretroviral treatment (HAART), which has significantly reduced HIV-associated morbidity and mortality rates. Accordingly, the prevalence of HIV-associated cardiac dysfunction may also have changed. The aim of the study was to establish the prevalence of right- and left-sided cardiac dysfunction in a Danish HIV population, most of whom were undergoing HAART, with radionuclide ventriculography. Ninety-five consecutive patients with HIV infection were included. Mean HIV duration was 104 months, and 84% of the patients received HAART. All patients underwent radionuclide ventriculography, and plasma levels of atrial natriuetic peptide (ANP), brain natriuetic peptide (BNP), and endothelin-1 (ET-1) were measured. Thirty age- and sex-matched healthy volunteer subjects were included to establish reference values of radionuclide measurements of left and right ventricular ejection fraction and of left ventricular volume. Of 95 patients with HIV, 1 (1%) had a reduced left ventricular ejection fraction and 6 (7%) had a reduced right ventricle ejection fraction (0.35-0.42) compared with reference values from the age- and sex-matched reference population. Patients with HIV and reduced cardiac function did not differ in the duration of HIV, CD4 count, CD4 nadir, or HIV RNA load. No correlations were found between reduced cardiac function and levels of the 3 peptides measured. No major dysfunction of the left ventricle is present in a developed world HIV population. However, a small but significant part of this population has modestly reduced right-sided systolic function.


[Electronic medical record and prescription: risks and benefits detected since its implementation. Safe designing, rollout and use].
New information technologies have transformed the way care is delivered within health services, permeating almost every aspect of health care. As the complexity of the system increases, it becomes more difficult to work optimally without the assistance of new technologies. Although its implementation represents a breakthrough, either because of the advancement involved in the proper use of any technology in health care, or because of the development of specific applications that improve patient safety, other factors such as incorrect design, implementation and poor maintenance, inadequate training, along with overconfidence and dependency, can make technologies compromise patient safety. This article describes the beneficial effects, and those that are not so, of the introduction in our country of the electronic medical record and the electronic prescription on the healthcare quality and safety.


Ascorbic acid transport by a clonal line of pheochromocytoma cells.
A clonal line of rat pheochromocytoma cells was used as a model of noradrenergic tissue to study ascorbic acid transport. These cells were used because, like sympathetic neurons, they synthesize large amounts of noradrenaline in the presence of ascorbate, they respond to nerve growth factor with the production of neurites and they release, store and take up catecholamines. In these cells, both with and without nerve growth factor (NGF) treatment, [14C]ascorbic acid was concentrated by a stereospecific saturable, energy dependent transport system that could be described by a Michaelis-Menten transport model. The Kt and Vmax for ascorbic acid were approximately 0.03 mM and 0.3 nmole per min per mg protein respectively for both untreated and NGF-treated cells. The ability of the cells to concentrate ascorbic acid was not due to intracellular binding. Cells untreated with NGF and loaded with [14C]ascorbic acid to a concentration of 5.6 nmoles per mg protein retained only 6% of the initial intracellular [14C]ascorbic acid after the 24 h in normal growth medium. Thus, although pheochromocytoma cells contain an ascorbate concentrating system, optimal production of noradrenaline requires ascorbate in the medium.


Does cognitive behavioral therapy for youth anxiety outperform usual care in community clinics? An initial effectiveness test.
Most tests of cognitive behavioral therapy (CBT) for youth anxiety disorders have shown beneficial effects, but these have been efficacy trials with recruited youths treated by researcher-employed therapists. One previous (nonrandomized) trial in community clinics found that CBT did not outperform usual care (UC). The present study used a more stringent effectiveness design to test CBT versus UC in youths referred to community clinics, with all treatment provided by therapists employed in the clinics. A randomized controlled trial methodology was used. Therapists were randomized to training and supervision in the Coping Cat CBT program or UC. Forty-eight youths (56% girls, 8 to 15 years of age, 38% Caucasian, 33% Latino, 15% African-American) diagnosed with DSM-IV anxiety disorders were randomized to CBT or UC. At the end of treatment more than half the youths no longer met criteria for their primary anxiety disorder, but the groups did not differ significantly on symptom (e.g., parent report, eta-square = 0.0001; child report, eta-square = 0.09; both differences favoring UC) or diagnostic (CBT, 66.7% without primary diagnosis; UC, 73.7%; odds ratio 0.71) outcomes. No differences were found with regard to outcomes of comorbid conditions, treatment duration, or costs. However, youths receiving CBT used fewer additional services than UC youths (χ(2)(1) = 8.82, p = .006). CBT did not produce better clinical outcomes than usual community clinic care. This initial test involved a relatively modest sample size; more research is needed to clarify whether there are conditions under which CBT can produce better clinical outcomes than usual clinical care. CLINICAL TRIAL REGISTRY INFORMATION: Community Clinic Test of Youth Anxiety and Depression Study, URL: http://clinicaltrials.gov, unique identifier: NCT01005836.


W-7, a calmodulin inhibitor, potentiates dacarbazine cytotoxicity in human neoplastic cells.
Dacarbazine induces damage in replicative DNA, with a maximum level at 24 hr after treatment. Repair of these lesions does not occur when cells are post-treated with the calmodulin inhibitor W-7. In parallel cell cytotoxicity increases. The augmentation effect of W-7 is prevented by simultaneous incubation of cells with high levels of calmodulin and does not occur in cells pre-treated with aphidicolin (to stop DNA synthesis). Furthermore, W-5, an analogue of W-7 with a less inhibitory effect on calmodulin, does not interfere with DNA repair. The results show that calmodulin and/or calmodulin-regulated proteins are involved in the repair process of dacarbazine-induced DNA lesions.


Physicians' patient load per DRG, the consumption of hospital resources, and the incentives of the DRG prospective payment system.
From 1985 through 1987, the authors assessed the relationship between two main variables at a large academic medical center: (1) the numbers (high or low) of patients per diagnosis-related group (DRG) treated by individual physicians and (2) hospital resource consumption of the patients. The patients were classified according to their routes of admission (emergency or non-emergency); the physicians with eight or more patients per DRG were labeled "high-patient-load physicians" (hereafter called "high-load physicians"), and those with five or fewer patients were labeled "low-patient-load physicians," ("low-load physicians"). The resource variables studied were length of stay (LOS) and total hospital cost. For the non-emergency admissions, the low-load physicians' patients had an average LOS that was 56.2% greater and an average hospital cost that was 58.3% greater than were the LOS and cost of the patients of the high-load physicians. (Both LOS and cost per patient were adjusted for DRG weight index.) This was due in part to a greater severity of illness for the patients (as measured by total ICD-9-CM codes per patient) of the low-load physicians. For the emergency admissions, the low-load physicians' patients had an average LOS that was 9.5% greater and an average hospital cost that was 10.5% greater than the LOS and cost of the patients of the high-load physicians. As in the non-emergency admissions group, severity of illness for the patients of the low-load physicians was greater. The only category of patients that was economically profitable to the hospital was the non-emergency admissions group treated by the high-load physicians. Even though these findings were the result of many factors (discussed in the text), they suggest a relationship between hospital resource consumption and the physicians' patient load per DRG.


Intrapulmonary shunt in the course of pediatric liver transplantation.
The hepatopulmonary syndrome occurs when an intrapulmonary shunt (IPS) causes hypoxemia in patients with cirrhosis. Because IPS has not been clearly defined in children, we investigated the prevalence, clinical characteristics, and outcomes of IPS in children undergoing liver transplantation (OLT). Of the 107 pediatric OLT recipients between December 1994 and March 2005, 18 (16.8%) had IPS, as evaluated by contrast-enhanced echocardiography (CEE) at 9 months to 16 years of age. The degree of IPS was classified into five grades according to the extent of microbubbles in the left ventricle, with significant IPS defined as grade II or higher. Baseline characteristics, including serum total bilirubin, albumin, aminotransferase, and prothrombin time, did not differ in patients with or without IPS. The patients with IPS had significantly lower Pao2 and Sao2, longer duration of mechanical ventilation and hospital stay, and higher postoperative morbidity and mortality than patients without IPS (P < .05 each), but there were no other significant differences between the groups. The six patients with significant IPS (one grade II, three grade III, and two grade IV) showed a significantly greater morbidity and mortality than patients with grade I IPS (P < .05). Most of the positive CEE findings of IPS regressed within 6 months after OLT. These findings indicated that IPS is not uncommon among children undergoing OLT, but is reversible. Because severe IPS may increase patient morbidity and mortality, early assessment of IPS status using CEE is essential for pediatric OLT candidates.


Electrically stimulated resistance training in SCI individuals increases muscle fatigue resistance but not femoral artery size or blood flow.
Longitudinal. The purpose of this study was to evaluate the effect of lower extremity resistance training on quadriceps fatigability, femoral artery diameter, and femoral artery blood flow. Academic Institution. Five male chronic spinal cord injury (SCI) individuals (American Spinal Injury Association (ASIA): A complete; C5-T10; 36+/-5 years old) completed 18 weeks of home-based neuromuscular electrical stimulation (NMES) resistance training. Subjects trained the quadriceps muscle group twice a week with four sets of 10 dynamic knee extensions against resistance while in a seated position. All measurements were made before training and after 8, 12, and 18 weeks of training. Ultrasound was used to measure femoral artery diameter and blood flow. Blood flow was measured before and after 5 and 10 min of distal cuff occlusion, and during a 4-min isometric electrical stimulation fatigue protocol. Training resulted in significant increases in weight lifted and muscle mass, as well as a 60% reduction in muscle fatigue (P = 0.001). However, femoral arterial diameter did not increase. The range was 0.44+/-0.03 to 0.46+/-0.05 cm over the four time points (P = 0.70). Resting, reactive hyperemic, and exercise blood flow did not appear to change with training. NMES resistance training improved muscle size and fatigue despite an absence of response in the supplying vasculature. These results suggest that the decreases in arterial caliber and blood flow seen with SCI are not tightly linked to muscle mass and fatigue resistance. In addition, muscle fatigue in SCI patients can be improved without increases in arterial diameter or blood flow capacity.


The use of SSCP analysis in the assessment of phytoplasma gene variability.
Single-strand conformation polymorphism (SSCP) analysis is a broadly used technique for detecting mutations. The aim of this work was to assess the applicability of SSCP as a new tool for the detection of the molecular variability of uncultivable mollicutes - phytoplasmas. Three phytoplasma regions were investigated: 16S rDNA, tuf gene, and dnaB gene. Fragments amplified by PCR were subjected to SSCP under conditions optimized for each fragment length. In all of the analyzed regions, SSCP revealed the presence of polymorphism undetected by routine RFLP analyses. Reliability of the method was confirmed by the multiple alignments and phylogenetic analyses of representative sequences showing different SSCP profiles.


Influence of ovarian cystectomy on the ovulatory function of the residual ovary.
Whether the surgery for benign ovarian disease affect ovulatory function on residual ovarian tissue has not yet been established. We investigated the post-operative function of residual ovaries in 62 patients who underwent laparoscopic ovarian cystectomy or abdominal ovarian cystectomy. The results based on an average of 7.9 monitored ovulatory cycles after surgery showed that 53% of patients did not have natural ovulation from the diseased ovary. The number of developing follicles after ovulation-induction treatments was significantly less in the diseased ovary than in the healthy ovary. However, in 13 of 24 women who became pregnant after surgery, ovulation occurred in the diseased ovary. Although a reduction in maturation of follicles was suggested after cystectomy, some women became pregnant after ovulation from the diseased ovary. Our results suggest that careful attention should be given to preventing post-operative adhesion in the diseased and surgically managed ovary in cases that undergo cystectomy.


Resection of the sciatic, peroneal, or tibial nerves: assessment of functional status.
Lower-extremity tumors are often treated by amputation rather than limb-sparing excision that sacrifices the sciatic nerve or a branch. This study assessed the functional outcome of major nerve sacrifice during limb-sparing resections for lower-extremity soft tissue sarcoma. Patients who underwent division of the sciatic, tibial, or peroneal nerve(s) during limb-sparing sarcoma surgery (January 1982 through June 2000) were identified. Eleven surviving patients evaluated their pre- and postoperative functional status by self-administered questionnaire (six sciatic, two tibial, and three peroneal nerve divisions). Eighteen patients (10 male, 8 female; 14-84 years old) had nine primary and nine locally recurrent tumors. Tumors were high (16) or low grade (two). Five patients died of disease and two died of other causes. Median overall survival was 50 months. One of 11 reported increased pain. Eight had new phantom sensations with a median intensity of 4.5 (1 = least; 10 = most). All patients used an ankle brace to walk after a sciatic (four) or peroneal (one) division. Walking ability and distance after surgery was unchanged (nine), improved (one), and worsened (one). Standing improved in 7 of 11 patients. Proprioception in the affected extremity was retained in six. The median postoperative leg functional score was 8 (1 = worst; 10 = best). No patient developed foot ulcers. One patient underwent amputation for recurrence. All patients preferred their status over having an amputation. Objectively and subjectively, division of the major lower-extremity nerves causes acceptable functional deficits in most patients. Resection of affected sciatic nerve (branches) during limb-sparing tumor surgery is an excellent alternative to amputation.


Kinetic study of the reaction of vitamin C with vitamin E radicals (tocopheroxyls) in solution.
New stable vitamin E radicals (7-tert-butyl-5-isopropyltocopheroxyl (4), 5,7-diisopropyltocopheroxyl (5), 7-tert-butyl-5-methyltocopheroxyl (6), and 5,7-diethyltocopheroxyl (7] with two bulky alkyl substituents at ortho positions (C-5 and C-7) have been prepared, and the reaction rates of vitamin C (ascorbic acid (1) and 6-O-stearyl ascorbic acid (2] with these tocopheroxyl radicals in benzene/ethanol/water (2:1:0.1, v/v) solution have been determined spectrophotometrically, using a stopped-flow technique. The second-order rate constants, k2, obtained vary in the order of 10(3), and decrease dramatically in the order 7 greater than 6 greater than 5 greater than 4, as the size of two ortho-alkyl groups in tocopheroxyl increases. The result suggests that the effect of steric hindrance on the reaction rate is considerable. These reaction rates were compared with those of vitamin C with alpha-tocopheroxyl reported by Packer et al. (Nature 278 (1979) 737-738) and Scarpa et al. (Biochim. Biophys. Acta 801 (1984) 215-219).


Probenecid sensitive pathway of elimination of dopamine and serotonin metabolites in CSF of the rat.
CSF was removed at a constant flow rate of 1 microliter/min from the third ventricle of anesthetized rats. Five microliter CSF samples were directly injected every 15 min into a liquid chromatographic system coupled with an amperometric detector. Mean CSF values for free dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA) and 5-hydroxyindolacetic acid (5-HIAA) were 1.4, 0.9, and 2.6 X 10(-6)M respectively. High doses of probenecid resulted in a linear increase of acidic metabolite concentrations which gave an index of the fractional turnover rates related to the resorption by the weak organic acid carrier. Accumulation rates were 0.24, 0.87, and 1.58 mumol/l/h for DOPAC, HVA and 5-HIAA respectively. This route of elimination was predominant for 5-HIAA while it represented only a small part of total turnover for DOPAC. A high elimination rate constant for HVA validates the use of control levels of this metabolite as an indication of fractional HVA turnover dependent upon probenecid-sensitive carrier.


Beyond the genomics blueprint: the 4th Human Variome Project Meeting, UNESCO, Paris, 2012.
The 4th Biennial Meeting of the Human Variome Project Consortium was held at the headquarters of the United Nations Educational, Scientific and Cultural Organization (UNESCO) in Paris, 11-15 June 2012. The Human Variome Project, a nongovernmental organization and an official partner of UNESCO, enables the routine collection, curation, interpretation, and sharing of information on all human genetic variation. This meeting was attended by more than 180 delegates from 39 countries and continued the theme of addressing issues of implementation in this unique project. The meeting was structured around the four main themes of the Human Variome Project strategic plan, "Project Roadmap 2012-2016": setting normative function, behaving ethically, sharing knowledge, and building capacity. During the meeting, the members held extensive discussions to formulate an action plan in the key areas of the Human Variome Project. The actions agreed on were promulgated at the Project's two Advisory Council and Scientific Advisory Committee postconference meetings.


Long-term dynamics of multiple sclerosis iron rim lesions.
Several studies have pointed out that seemingly chronic multiple sclerosis (MS) lesions may also be in inflammatory states. In pathological studies, up to 40% of chronic MS lesions are characterized as "chronic active" or "smoldering" lesions that are characterized by a rim of iron-laden proinflammatory macrophages/microglial cells at the lesion edge with low-grade continuous myelin breakdown. In vivo, these lesions can be visualized as "iron rim lesions" (IRLs) on susceptibility-weighted imaging (SWI). The aim of this study was to investigate the long-term dynamics of IRLs in vivo for a more detailed evolution of dynamic lesion volume changes occurring over time. We retrospectively identified patients with MS who were followed for at least 36 months (up to 72 months) and underwent at least an annual MRI on the same 3 Tsystem. Using Voxel-Guided Morphometry (VGM) we investigated regional volume changes within lesions and correlated these findings with SWI for the presence of a characteristic hypointense lesion rim. To estimate tissue damage, apparent diffusion coefficient (ADC) values for every lesion at baseline and follow-up MRIs were determined. Forty-three patients were included in the study. Overall, we identified 302 supratentorial non-confluent MS lesions (52 persistent IRLs, nine transient IRLs, 228 non-IRLs and 13 acute contrast-enhancing lesions). During follow-up, persistent IRLs significantly enlarged, whereas non-IRLs showed a tendency to shrink. At baseline MRI, ADC values were significantly higher in persistent IRLs (1.23 × 10-3 mm/s2) compared to non-IRLs (1.01 × 10-3 mm/s2; p < 0.001), but not compared to transient IRLs (1.06 × 10-3 mm/s2; p = 0.15) and contrast-enhancing lesions (1.15 × 10-3 mm/s2; p = 1.0). During follow-up, ADC values significantly increased more often in persistent IRLs compared to all other lesion types (p < 0.0001). Our long-term data demonstrate that persistent IRLs enlarge during disease duration, whereas non-IRLs show a tendency to shrink. Furthermore, IRLs are associated with sustained tissue damage, supporting the notion that IRLs could represent a new imaging biomarker in MS.


Steroidal saponins from the tubers of Dichelostemma multiflorum and their inhibitory activity on cyclic-AMP phosphodiesterase.
Phytochemical examination of the tubers of Dichelostemma multiflorum led to the isolation of three new steroidal saponins together with two known saponins. The structures of the new compounds were determined by spectral data and a few chemical transformations to be (25R)-5 alpha-spirostane- 1 beta,3 beta-diol (brisbagenin) 1-O-[O-alpha-L-rhamnopyranosyl-(1-->3)-4-O- acetyl-alpha-L-arabinopyranoside], brisgabenin 1-O-[O-alpha-L-rhamnopyranosyl-(1-->2)-O- [alpha-L-rhamnopyranosyl-(1-->3)]-4-O-acetyl-alpha-L-arabinopyranosid e] and (22S,25S)-5 alpha-spirostan-3 beta-o1 3-O-[O-beta-D-galactopyranosyl- (1-->2)-O-[beta-D-xylopyranosyl-(1-->3)]-O-beta-D-glucopyranosyl-(1-->4) -beta-D-galactopyranoside]. The known compounds were identified as desglucolanatigonin II and gitonin, with certain amounts of the corresponding C-25S isomers. Inhibitory activity of the isolated saponins and their derivatives on cAMP phosphodiesterase was evaluated to identify new compounds with medicinal potential.