Polyphenolic Profile and Varied Bioactivities of Processed Taiwanese Grown Broccoli: A Comparative Study of Edible and Non-Edible Parts.
Broccoli contains a substantial amount of bioactive compounds such as glucosinolates, phenolics, and essential nutrients, which are positively linked to health-promoting effects. This work aimed to evaluate whether both edible and non-edible parts of broccoli could be effective by examining in vitro antioxidant, cytotoxic, apoptotic, and antibacterial properties of its floret, leaf, and seed extracts (FE, LE, and SE, correspondingly). High-performance liquid chromatography (HPLC) and various assays exhibited strong antioxidant activities of all samples. LE obtained the highest capacity, correlated to its polyphenolic contents. SE exerted significant cytotoxicity against A549, Caco-2, and HepG2 cancer cell lines at low inhibitory concentration (IC)50 values (0.134, 0.209, and 0.238 mg/mL, respectively), as tested by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Flow cytometry confirmed apoptosis induction of extracts in Caco-2 cells by revealing an increased subG1 population and a decreased mitochondrial membrane potential. The considerable antibacterial efficacy was observed in either LE and SE against Bacillus subtilis and Salmonella typhimurium (0.39-0.78 mg/mL) using well-agar diffusion and minimum inhibitory concentration (MIC) techniques, along with the weak activity against Staphylococcus aureus and Escherichia coli (1.56-3.13 mg/mL). The findings suggest that broccoli and its byproducts might serve as a promising source for further development of food or pharmaceutical products.


Brief report: exposure and response prevention for obsessive compulsive disorder in a 12-year-old with autism.
Obsessive Compulsive Disorder (OCD) involves exaggerated or excessive worry about threatening and non-threatening stimuli coupled with impairing rituals believed to reduce anxiety. Autism Spectrum Disorders (ASD) are characterized by impairment in social and communicative activities as well as restricted and repetitive behaviors. Approximately 2% of children with ASD are also diagnosed with OCD. Although there is extensive research demonstrating the effectiveness of behavioral interventions for pediatric OCD, little is known about how effective these treatments are for children who have a dual diagnosis of OCD and ASD. This report describes a 12-year-old male with Autism who was treated successfully with cognitive behavioral therapy with exposure and response prevention. This case study provides initial support that cognitive-behavioral therapy is effective in symptom reduction for children with comorbid autism and OCD.


Four well-constrained calibration points from the vertebrate fossil record for molecular clock estimates.
Recent controversy about the use of the vertebrate fossil record for external calibration of molecular clocks centers on two issues, the number of dates used for calibration and the reliability of the fossil calibration date. Viewing matters from a palaeontological perspective, we propose three qualitative, phylogenetic criteria that can be used within a comparative framework for the selection of well-constrained calibration dates from the vertebrate fossil record. On the basis of these criteria, we identify three highly suitable new fossil calibration dates for molecular clock estimates: the lungfish-tetrapod split (between 419 and 408 Ma), the bird-crocodile split (between 251 and 243 Ma), and the alligator-caiman split (between 71 and 66 Ma). Together with our previously suggested bird-lizard split (between 252 and 257 Ma), these four fossil dates span a range of very different ages. They are, in our opinion, more suitable for molecular clock calibration than the traditionally used mammal-bird split, which is less well constrained. We plea for closer interactions between paleontologists and molecular biologists in studying the timescale of vertebrate evolution.


Synthetic Curcumin Analogs as Inhibitors of β -Amyloid Peptide Aggregation: Potential Therapeutic and Diagnostic Agents for Alzheimer's Disease.
There is a crucial need to develop new effective drugs for Alzheimer's disease (AD) as the currently available AD treatments provide only momentary and incomplete symptomatic relief. Amongst natural products, curcumin, a major constituent of turmeric, has been intensively investigated for its neuroprotective effect against β-amyloid (Aβ)-induced toxicity in cultured neuronal cells. The ability of curcumin to attach to Aβ peptide and prevent its accumulation is attributed to its three structural characteristics such as the presence of two aromatic end groups and their co-planarity, the length and rigidity of the linker region and the substitution conformation of these aromatics. However, curcumin failed to reach adequate brain levels after oral absorption in AD clinical trials due to its low water solubility and poor oral bioavailability. A number of new curcumin analogs that mimic the active site of the compound along with analogs that mimic the curcumin anti-amyloid effect combined with anticholinesterase effect have been developed to enhance the bioavailability, pharmacokinetics, water solubility, stability at physiological conditions and delivery of curcumin. In this article, we have summarized all reported synthetic analogs of curcumin showing effects on β-amyloid and discussed their potential as therapeutic and diagnostic agents for AD.


Self-assembled 20-nm (64)Cu-micelles enhance accumulation in rat glioblastoma.
There is an urgent need to develop nanocarriers for the treatment of glioblastoma multiforme (GBM). Using co-registered positron emission tomography (PET) and magnetic resonance (MR) images, here we performed systematic studies to investigate how a nanocarrier's size affects the pharmacokinetics and biodistribution in rodents with a GBM xenograft. In particular, highly stable, long-circulating three-helix micelles (3HM), based on a coiled-coil protein tertiary structure, were evaluated as an alternative to larger nanocarriers. While the circulation half-life of the 3HM was similar to 110-nm PEGylated liposomes (t1/2=15.5 and 16.5h, respectively), the 20-nm micelles greatly enhanced accumulation within a U87MG xenograft in nu/nu rats after intravenous injection. After accounting for tumor blood volume, the extravasated nanoparticles were quantified from the PET images, yielding ~0.77%ID/cm(3) for the micelles and 0.45%ID/cm(3) for the liposomes. For GBM lesions with a volume greater than 100mm(3), 3HM accumulation was enhanced both within the detectable tumor and in the surrounding brain parenchyma. Further, the nanoparticle accumulation was shown to extend to the margins of the GBM xenograft. In summary, 3HM provides an attractive nanovehicle for carrying treatment to GBM.


Functional Fatigue Alters Lower-extremity Neuromechanics during a Forward-side Jump.
Neuromuscular fatigue impairs neuromuscular control of the lower extremity. The purpose of the study was to investigate the effect of functional fatiguing exercises on sagittal-plane lower-extremity neuromechanics during a forward-side jump. 21 participants performed 5 forward-side jump tasks before and after functional fatiguing exercises. A functional analysis of variance (FANOVA) evaluated differences between 2 different conditions (pre- vs. post-fatigue) for joint angle, moment, and EMG amplitude during stance of a forward-side jump. FANOVA compared variables as polynomial functions, and differences between functions with 95% confidence interval bands were plotted to determine significant differences. Plantar, knee, and hip flexion decreased during the initial stages of landing following fatigue. Plantarflexion moment decreased during 10-20% of stance in post-fatigue. Knee extension moment initially increased while decreased during 20-30% of stance following fatigue. Hip extension moment initially decreased while increased at 20% of stance. Tibialis anterior EMG decreased during 30-40% of stance, vastus lateralis EMG increased at 15% of stance, hamstring EMG decreased at foot contact and during 25-60% of stance, and gluteus maximus EMG decreased at foot contact and 35% of stance. The functional fatiguing exercises resulted in a more upright landing position, potentially indicating a greater reliance upon skeletal structures for support.


Real-time intraoperative detection of melanoma lymph node metastases using recombinant vaccinia virus GLV-1h68 in an immunocompetent animal model.
There is a clinical need for improved intraoperative detection of lymph node metastases from malignant melanoma (MM). We aimed to investigate the use of recombinant vaccinia virus GLV-1h68, expressing green fluorescent protein (GFP), for real-time intraoperative detection of melanoma lymph node metastases in an immunocompetent animal model. Mice bearing foot pad tumors received intratumoral injections of GLV-1h68, and 48 hr later were evaluated for popliteal lymph node metastasis using noninvasive bioluminescence imaging and fluorescence imaging. Histologic analysis of lymph nodes was performed to determine sensitivity and specificity of virus-mediated detection. Intratumoral injection of GLV-1h68 into primary foot pad melanoma tumors resulted in viral transmission to popliteal lymph nodes, infection of lymphatic metastases, and transgene expression that was reliably and easily detected. Histologic confirmation demonstrated favorable operating characteristics of this assay (sensitivity 80%, specificity 100%, positive predictive value [PPV] 100%, negative predictive value [NPV] 91%). Detection of marker gene expression by GLV-1h68 allowed the detection of lymphatic metastases in an immunocompetent animal model of MM. This assay is rapid, sensitive, specific and easy to perform and interpret. As a candidate gene therapy virus for killing cancer, GLV-1h68 may also have significant concomitant diagnostic utility in the staging of cancer patients.


Photoionization versus photoheterolysis of all-trans-retinol. The effects of solvent and laser radiation intensity.
The time-resolved formation of the retinyl carbocation from all-trans-retinol and all-trans-retinol acetate was studied by use of picosecond flash photolysis. From both precursors, the retinyl cation is produced by heterolytic C-O bond cleavage in solvents of medium polarity (acetonitrile, tetrahydrofuran, propanol with Reichardt polarity parameter ET(N) approximately 0.5) and high polarity (EtOH, MeOH, TFE, HFIP, ET(N) > 0.6) during the laser pulse (< or =5 ps) where its lifetime is >10 ns. The absorption maximum of the cation at early times (t < 100 ps) is at lambda = 590-600 nm; it shifts to shorter wavelengths (Deltalambda = 5-10 nm) within 1-10 ns. This spectral shift is suggested to be due to contact ion pair --> solvent-separated ion pair --> free-ion transformation. The quantum yield of cation formation phi(cat) is independent of excitation wavelength (213, 266 or 355 nm). Photoheterolysis proceeds via a one-quantum process. In chlorinated solvents, i.e. n-BuCl, 1,2-dichloroethane, chloroform or CCl(4), formation of the retinol radical cation (which is characterized by a peak at 610 nm and further absorption maxima at approximately 840 and approximately 940 nm) by intermolecular electron transfer to the solvent molecules was detected. The radical cation lifetime in all these solvents is 1.5-2 ns, except for CCl(4) where it is 0.25 ns. The formation of the radical cation or cation was not detected in the low polarity solvents: cyclohexane, hexane, dioxane and p-xylene. However, in solvents of medium and high polarity, at high radiation intensities the radical cation may form in addition to the cation (as a result of two-quantum ionization). DFT calculations confirm our experimental results. The rate of retinol S(1) depopulation (k = 0.3-1 x 10(9) s(-1)) is almost independent of the solvent polarity in the range from cyclohexane to methanol. In highly polar solvents (ET(N) > 0.9) the rate increases to (0.5-5) x 10(10) s(-1).


Should the Same Safety Scrutiny of Antiobesity Medications be Applied to Other Chronic Usage Drugs?
Obesity treatment is highly stigmatized, mainly because of the stigma of obesity itself. The frequent withdrawal of medications, lorcaserin being the last example, contributes to this stigma, but it is also probably a reflection of it, as data suggest that the threshold for a withdrawal is lower than with other classes of drugs. Safety should always be an absolute priority for every new medication, especially when used on a chronic basis; however, the safety scrutiny given to antiobesity medications is not given for other medications, such as postmenopausal hormone therapy and central nervous system drugs for psychiatric use. The withdrawal of medications for obesity can also impact future research in the area, so we need transparency and equality. Transparency in knowing exactly what reason led to a drug being discontinued and equality in long-term safety should be a concern with any medication prescribed for chronic diseases.


Self-help groups for parents of young drug and alcohol abusers.
A national movement of parent self-help groups has recently emerged to combat drug abuse in children and adolescents. This innovative modality addresses a major mental health problem in an area where manpower shortages are anticipated. On the basis of self-report data from 135 parent group members, the drug and behavior problems of their children were evaluated. Improvement was reported in the community at large but more frequently in the children of members. The parent groups differed notably in structure and activities; nonetheless, the underlying psychology of membership, i.e., the shared attitudes and social cohesiveness of the members, facilitated the achieving of common goals.


Investigating the association between socioeconomic and agricultural risk factors and the incidence of Salmonella Heidelberg and Salmonella Typhimurium in Ontario in 2015: A multi-level ecological approach.
The incidence of salmonellosis, and other enteric zoonotic diseases, has been associated with various food and environmental exposures and socioeconomic factors. Increasingly, there is interest in exploring differences among serotypes of Salmonella to better inform public health prevention efforts. Consequently, we investigated whether rates of Salmonella Heidelberg and Typhimurium in Ontario communities in 2015 were influenced by household characteristics, agricultural factors, and the presence of meat plants. Data for each reported case of S. Heidelberg and S. Typhimurium in Ontario in 2015 were collected. Expected cases of each serotype were calculated, stratified by age group and sex, according to the underlying population distribution from the Canadian census. Socioeconomic, agricultural census data, and data concerning provincial and federally inspected meat plants were combined with observed and expected case counts. The association between community-level agricultural, meat processing, and socioeconomic variables, serotype, and the rate of salmonellosis in each census subdivision (CSD) was explored using multilevel Poisson models, with random intercepts for CSD and census division (CD). Rates of S. Heidelberg and S. Typhimurium were associated with the proportion of married individuals in a CSD, and were higher in CSDs with the highest quantile of labour participation compared to those in the lowest quantile. There was an interaction effect between cattle, poultry and swine farm density in a CD and serotype, with rates of either serotype decreasing as cattle, poultry, or swine farm density in the encompassing CD increased. The rate of the decrease varied by serotype. Our findings concerning community-level household characteristics may be explained by the influence of family structure and occupation on food consumption patterns and environmental exposures. Rates of S. Heidelberg and S. Typhimurium may be lower in areas with increased animal farm density due to naturally acquired immunity from routine exposure to Salmonella via livestock.


[Pleuropneumoblastoma: a case report about a rare pediatric tumor].
Pleuropulmonary blastoma is a rare intrathoracic tumor in children. It is associated with poor prognosis and diagnosis is based on histological examination. We conducted a didactic study involving a 3-year-old child with severe acute respiratory distress associated with hemothorax; radiological and thoracoscopic examination suggested malignant pleuropulmonary process. Anatomopathological examination with radio-clinical comparison allowed for the diagnosis of solid-cystic pleuropulmonary blastoma type II. Unfortunately, given the severity of the clinical features, the child died within a few weeks due to multiple organ failure. Pathologist experience is very important to recognize the disease and to start adequate treatment as soon as possible. This allows for a tumor regression rate up to 90% after neoadjuvant treatment and a 5-year survival rate of at least 53% for aggressive forms: solid and solido-cystic tumors.


Central nervous system complications of acute tonsillitis.
Acute tonsillitis is a common infection of early childhood which may even run a self-limiting course without antibiotic therapy in some cases. Complications are encountered infrequently and rarely assume a life-threatening propensity. Central nervous system involvement has not to our knowledge been described in association with tonsillitis without local abscess formation. We describe three cases in which acute tonsillitis/peritonsillitis was complicated by major central neurological sequelae. The neurological complications encountered in young previously healthy adults were: facial palsy and hemiplegia; superior sagittal sinus thrombosis with communicating hydrocephalus and papilloedema; Guillain-Barré syndrome and facial palsy. The pathogenesis and management is discussed. All patients made satisfactory recoveries, though with minor residual neurological disabilities.


Evaluation of Protein Bait Manufactured From Brewery Yeast Waste for Controlling Drosophila suzukii (Diptera: Drosophilidae).
We evaluated a protein bait based on an enzymatically hydrolyzed beer yeast and two widely used baits including a sugar + vinegar + wine mixture and apple cider vinegar for their ability to trap Drosophila suzukii (Matsumura) in the laboratory and outdoors. The protein bait was a more attractive lure than the other tested baits, with the protein bait capturing significantly more female and male adults at different developmental stages than the other baits. Furthermore, the protein bait with 20% vinegar attracted significantly more adult flies than the other baits, and the protein bait without dilution attracted the most adults. Except for the addition of 0.05% spinosad, increased insecticide content in protein bait reduced its attractiveness to adult flies. Moreover, we found that D. suzukii has a bimodal activity pattern in visiting protein bait, where maximum activity occurs during 8:00-10:00 a.m. and 14:00-16:00 p.m. The antennae and maxillary palpi played an important role in detecting the chemicals emitted from the protein bait, as the number of intact flies that responded to new protein bait was significantly higher than the number of flies without antennae that responded, but almost 15% of defective flies still responded to the protein bait. Our results suggested that the protein bait based on spent brewery yeast could be a promising alternative for D. suzukii population monitoring and for managing this pest when combined with bioinsecticides, providing guidance for using this protein bait as a component of integrated pest management.


Effects of hypoxia on vasopressin concentrations in cerebrospinal fluid and plasma of sheep.
The relationship between concentrations of vasopressin in plasma and cerebrospinal fluid (CSF) was examined under basal and hypoxic conditions in unanesthetized and unrestrained adult female sheep. Under basal conditions mean (+/- SE) concentration of vasopressin (4.1 +/- 0.3 pg/ml) in CSF was significantly (p less than 0.001) higher than the concentration in arterial plasma (2.4 +/- 0.2 pg/ml). There was a significant positive correlation between CSF and plasma vasopressin concentrations (r = 0.66, p less than 0.01). The introduction of severe hypoxia by exposure of the sheep to an inspired gas mixture of 5% O2 in N2, a known stimulus to systemic release of vasopressin, was associated with an increase in the concentration of vasopressin in plasma to 339 +/- 65 pg/ml and CSF to 19 +/- 3.9 pg/ml. This increase of vasopressin in CSF was delayed in time with respect to the increases in the plasma and of a lesser magnitude. With moderate hypoxia (10% O2 in N2 exposure) no increase in CSF or plasma vasopressin concentration was observed, suggesting a threshold response. Intravenous infusion of vasopressin to achieve plasma values comparable to those seen with hypoxia was not accompanied by a significant increase in CSF vasopressin concentration. Thus, severe hypoxia is a potent stimulus for release of vasopressin into both CSF and plasma. Furthermore, data suggest that vasopressin may be released into CSF via a separate route from that released into plasma.


Ovarian cancer and unilateral naevoid telangiectasia: a rare association.
The Authors describe the case of a 58-year-old woman affected by erythematous telangiectasis lesions on the antero-lateral surface of the right hip during papillary serous cystoadenocarcinoma of the right ovary. The diagnosis, based on clinical and histological findings, was unilateral naevoid telangiectasia. After a review of literature the Authors assume a possible role of the oestrogens in the pathogenesis of such infrequent disease.


Body segment contributions to height achieved during the flight a springboard dive.
The way in which athletes achieve the necessary height to accomplish the rotational requirements of springboard dives was investigated by focusing upon the take-offs of dives from the forward and reverse groups. Films of eight women in the 3-m final of the 1982 Canadian championship and of five men practicing for the 1979 Fort Lauderdale Invitational Meet provided data for the analysis. The vertical acceleration of the diver's center of gravity was expressed relative to that of the metatarsals, which represented the point on the board directly beneath the feet. The divers were only able to accelerate upward relative to the metatarsals for approximately the first half of springboard depression. This period of positive relative acceleration was considered to be a key factor in effective deflection of the springboard. The lower extremities were responsible for about three-quarters of the diver's vertical acceleration during this period. Two-thirds of their contribution was attributed to their role in accelerating the large mass of the trunk upward. The upper extremities accounted for about 10% of the diver's vertical acceleration during the initial half of springboard depression. Their acceleration-time patterns clearly fell into three classifications depending upon whether their upward acceleration relative to the shoulders preceded, coincided with, or followed initial contact with the board for the take-off.


Diffusion tensor imaging in studying white matter complexity: a gap junction hypothesis.
The role of the prefrontal cortex as an executive oversight of posterior brain regions raises the question of the extent to which the anterior regions of the brain interconnect with the posterior regions. The aim of this study is to test the complexity of rostral white matter tracts, which connect anterior and posterior brain regions, in comparison to caudal white matter tracts and the corpus callosum. Diffusion tensor imaging (DTI) is a modality that measures fractional anisotropy (FA). Higher white matter complexity could result in a decrease of FA, possibly through denser intersection of fiber tracts. DTI was used to determine regional FA in 9 healthy bonnet macaques (Macaca radiata). Four regions of interest were included: anterior and posterior limbs of the internal capsule, the occipital lobe white matter, and the corpus callosum. FA of the anterior limbs of the internal capsule was lowest compared to all other regions of interest (Newman-Keuls (N-K); p<0.0001), whereas FA of the corpus callosum was highest (N-K; p<0.0001). The posterior limbs of the internal capsule and the occipital white matter were not distinguishable but exhibited intermediate FA in comparison to the former (N-K; p<0.0001) and the latter (N-K; p<0.0001). The current study demonstrates that FA, a measure of white matter complexity, can vary markedly as a function of region of interest. Moreover, validation of these findings using neurohistological studies and replication in human samples appears warranted.


Truly enthralling: epileptiform events in film and on television--why they persist and what we can do about them.
Seizures and epilepsy have been portrayed in film since 1900 and on television since the 1950s, but unlike many other conditions, their depictions have not improved with increased scientific understanding. At this time, most individuals who are under 45 years of age will never witness a seizure. Thus, their information about what seizures are comes from depictions in film and on television. Because especially on television these fictive and often erroneous images are increasing, many think of them as accurate. The research addresses three questions in relation to these images: How do directors use the images? Why do uses of seizures in visual media not reflect contemporary scientific knowledge? Why have they persisted and increased in use? Data consist of material from 242 films and television episodes. The general category of seizures includes seizures in characters said to have epilepsy or some other condition, seizures related to alcohol/drug use, feigned or pseudoseizures, and a "throwaway" category. The research demonstrates how epileptiform events drive the narrative, support the genre, evoke emotional reactions, highlight traits of characters with seizures, accentuate traits of other characters through their responses, act as catalysts for action, and enhance voyeuristic experience. Through connecting categories, we explain a basic social process (Glaser, 2007). The conclusion is that these images are so enthralling that their use is likely to persist. The authors suggest that advocates acknowledge this and then find ways to have more continuing characters with correctly depicted epilepsy be part of television series as a way of exploring the truly enthralling dimensions of the condition.


Comparison of surgical outcomes for small hepatocellular carcinoma in patients with hepatitis B versus hepatitis C: a Chinese experience.
Although both hepatitis B virus (HBV) and hepatitis C virus (HCV) infection are well recognized risk factors for hepatocellular carcinoma (HCC), little is known with respect to how HBV and HCV infection affect HCC recurrence in postoperative HCC Chinese patients. The objective of this study was to determine if differences exist in preoperative characteristics and postoperative HCC recurrence in patients with different HBV and HCV infection status. The study population consisted of 413 patients undergoing a curative resection at Tianjin Cancer Hospital for small HCC (< or =3 cm) from January 1997 to December 2003. The patients were divided into four groups: HCV only (n = 75), HBV only (n = 251), HBV and HCV (n = 33), and neither HBV nor HCV (NBNC, n = 54). The preoperative status and postoperative HCC recurrence were recorded. Survival analyses were used to assess the impact of HBV/HCV status on HCC recurrence. Patients with HCV had a significant association with older age, lower mean preoperative platelet counts and albumin levels, higher mean prothrombin time, alanine aminotransferase and total bilirubin levels and multinodular tumors during diagnosis. Patients with HCV also had significantly less differentiated tumors and a higher incidence of vascular invasion and cirrhosis when compared to the other groups. During the follow-up, the HCV group showed a higher incidence of intrahepatic recurrence and multiple recurrent lesions than the other patients. Patients with HCV infection tended to be older, and were characterized by more severe cirrhosis and higher incidence of tumor multicentricity. The statistically significant determinants for reoccurrence in patients with small HCC were HCV infection, presence of vascular invasion and multiple tumors.


Dynamic and structural aspects of PEGylated liposomes monitored by NMR.
Proton-detected NMR diffusion and (31)P NMR chemical shifts/bandwidths measurements were used to investigate a series of liposomal formulations where size and PEGylation extent need to be controlled for ultrasound mediated drug release. The width of the (31)P line is sensitive to aggregate size and shape and self-diffusion (1)H NMR conveys information about diffusional motion, size, and PEGylation extent. Measurements were performed on the formulations at their original pH, osmolality, and lipid concentration. These contained variable amounts of PEGylated phospholipid (herein referred to as PEG-lipid) and cholesterol. At high levels of PEG-lipid (11.5 and 15 mol%) the self-diffusion (1)H NMR revealed the coexistence of two entities with distinct diffusion coefficients: micelles (1.3 to 3x10(-11) m(2)/s) and liposomes (approximately 5x10(-12) m(2)/s). The (31)P spectra showed a broad liposome signal and two distinct narrow lines that were unaffected by temperature. The narrow lines arise from mixed micelles comprising both PEG-lipids and phospholipids. The echo decay in the diffusion experiments could be described as a sum of exponentials revealing that the exchange of PEG-lipid between liposomes and micellar aggregates is slower than the experimental observation time. For low amounts of PEG-lipid (1 and 4.5 mol%) the (31)P spectra consisted of a broad signal typically obtained for liposomes and the diffusion data were best described by a single exponential decay attributed solely to liposomes. For intermediate amounts of PEG-lipid (8 mol%), micellization started to occur and the diffusion data could no longer be fitted to a single or bi-exponential decay. Instead, the data were best described by a log-normal distribution of diffusion coefficients. The most efficient PEG-lipid incorporation in liposomes (about 8 mol%) was achieved for lower molecular weight PEG (2000 Da vs 5000 Da) and when the PEG-lipid acyl chain length matched the acyl chain length of the liposomal core phospholipid. Simultaneously to the PEGylation extent, self-diffusion (1)H NMR provides information about the size of micelles and liposomes. The size of the micellar aggregates decreased as the PEG-lipid content was increased while the liposome size remained invariant.


Influence of transcranial magnetic stimulation on spike-wave discharges in a genetic model of absence epilepsy.
Transcranial magnetic stimulation (TMS) impulses, (0.5 Hz, 3 impulses) were presented at threshold intensity to male WAG/Rij rats. One group received stimuli, which involved motor responses of hindlimbs, rats of the second group received sham stimulation. Electrocorticograms (ECoG) were recorded before and up to 2 hr from the moment of transcranial magnetic stimulation. It was established that such stimulation engendered a reduction of spike-wave discharge (SWD) bursts duration. This effect was most pronounced in 30 min from the moment of cessation of stimulation, when a decrease of 31.4% was noted in comparison with sham-stimulated control group. The number of bursts of spike-wave discharges was reduced, but did not reach significant difference when compared both with pre-stimulative base-line level and with sham-stimulated control rats. Bursts of spike-wave discharges restored up to pre-stimulative level in 90-150 minutes from the moment of cessation of transcranial stimulation. It can be concluded that transcranical magnetic stimulation possessed an ability to engender short-time suppression of bursts of spike-wave discharges in WAG/Rij rats.


The model barnacle Balanus balanus Linnaeus, 1758 (Crustacea: Maxillopoda: Sessilia) mitochondrial genome and gene rearrangements within the family Balanidae.
Balanus balanus Linnaeus, 1758, the model organism in the order Sessilia (Crustacea: Maxillopoda) is a cold water acorn barnacle in the family Balanidae distributing over the entire northern hemisphere. We present complete mitochondrial genome of this barnacle and analyze mitochondrial genomic characters of the family Balanidae. The length of mitochondrial genome is 15,955 bp, which is larger than those of the other barnacles in the same family. An inversion of a six-gene block (trnPro- nad4L- nad4- trnHis- nad5- trnPhe) is found between B. balanus and two Megabalanus (M. ajax and M. volcano). Three types of mitochondrial gene arrangements revealed in Balanidae have indicated the non-conserved gene orders even at intrafamilial level. Compared to pancrustacean ground pattern, large-scale gene rearrangements are found in B. balanus. Translocations of at least six tRNAs (trnAla, trnGlu/trnSer(AGY), trnPro/trnThr, trnLys, trnGln and trnCys) are identified and translocation and inversion occurred simultaneously in one tRNAs (trnTyr).


Effects of long-term CAPD on carbohydrate and lipid metabolism.
Long-term follow-up of CAPD patients indicates that these patients are at relatively low risk for developing de novo diabetes mellitus. Transperitoneal glucose absorption and the blood glucose and serum insulin response to the glucose load remain relatively unchanged with time. Alterations in lipid metabolism do occur; there is a tendency for the triglyceride levels to increase after 1 year and to maintain these high values with time. Total HDL cholesterol and its subfractions HDL2 and HDL3 remain unchanged and in the low normal range. Apoprotein A1 levels increase after 1 year and are maintained in the normal range.


Sustained increases in skin blood flow are not a prerequisite to initiate sweating during passive heat exposure.
Some studies have observed a functional relationship between sweating and skin blood flow. However, the implications of this relationship during physiologically relevant conditions remain unclear. We manipulated sudomotor activity through changes in sweating efficiency to determine if parallel changes in vasomotor activity are observed. Eight young men completed two trials at 36°C and two trials at 42°C. During these trials, air temperature remained constant while ambient vapor pressure increased from 1.6 to 5.6 kPa over 2 h. Forced airflow across the skin was used to create conditions of high (HiSeff) or low (LoSeff) sweating efficiency. Local sweat rate (LSR), local skin blood flow (SkBF), as well as mean skin and esophageal temperatures were measured continuously. It took longer for LSR to increase during HiSeff at 36°C (HiSeff: 99 ± 11 vs. LoSeff: 77 ± 11 min, P < 0.01) and 42°C (HiSeff: 72 ± 16 vs. LoSeff: 51 ± 15 min, P < 0.01). In general, an increase in LSR preceded the increase in SkBF when expressed as ambient vapor pressure and time for all conditions (P < 0.05). However, both responses were activated at a similar change in mean body temperature (average across all trials, LSR: 0.26 ± 0.15 vs. SkBF: 0.30 ± 0.18°C, P = 0.26). These results demonstrate that altering the point at which LSR is initiated during heat exposure is paralleled by similar shifts for the increase in SkBF. However, local sweat production occurs before an increase in SkBF, suggesting that SkBF is not necessarily a prerequisite for sweating.


Cannabinoid Receptor Type II Ligands from Sandalwood Oil and Synthetic α-Santalol Derivatives.
Bioassay-guided fractionation of the essential oil of Santalum album led to the identification of α-santalol (1) and β-santalol (2) as new chemotypes of cannabinoid receptor type II (CB2) ligands with Ki values of 10.49 and 8.19 μM, respectively. Nine structurally new α-santalol derivatives (4a-4h and 5) were synthesized to identify more selective and potent CB2 ligands. Compound 4e with a piperazine structural moiety demonstrated a Ki value of 0.99 μM against CB2 receptor and did not show binding activity against cannabinoid receptor type I (CB1) at 10 μM. Compounds 1, 2, and 4e increased intracellular calcium influx in SH-SY5Y human neuroblastoma cells that were attenuated by CB2 antagonism or inverse agonism, supporting the results that these compounds are CB2 agonists. Molecular docking showed that 1 and 4e had similar binding poses, exhibiting a unique interaction with Thr114 within the CB2 receptor, and that the piperazine structural moiety is required for the binding affinity of 4e. A 200 ns molecular dynamics simulation of CB2 complexed with 4e confirmed the stability of the complex. This structural insight lays a foundation to further design and synthesize more potent and selective α-santalol-based CB2 ligands for drug discovery.


Ethnic density and risk of mental ill health - The case of religious sectarianism in Northern Ireland: A population data linkage study.
An ethnic group that lives in a neighbourhood in which it is in the minority, termed 'lower ethnic density,' tends to report a higher incidence of mental ill-health. This population-based study investigated for the first time the existence of an own-group density effect among Catholic and Protestant communities in Northern Ireland. The entire Northern Ireland born Catholic and Protestant working age (n = 1, 004,060) enumerated population in the 2011 Census of Northern Ireland were included in the study via administrative data-linkage methodology. Catholics had a greater likelihood of reporting mental ill health in neighbourhoods with the largest proportion of Catholics (OR = 1.25, 95%CI 1.07-1.47), whereas mental health among Protestants was not associated with neighbourhood proportion of Protestants, after adjusting for socio-economic status and neighbourhood deprivation. The results indicate that a complex relationship exists between group identity, population composition of ethnic and religious groups and prevalence of community mental health.


On-surface synthesis of aligned functional nanoribbons monitored by scanning tunnelling microscopy and vibrational spectroscopy.
In the blooming field of on-surface synthesis, molecular building blocks are designed to self-assemble and covalently couple directly on a well-defined surface, thus allowing the exploration of unusual reaction pathways and the production of specific compounds in mild conditions. Here we report on the creation of functionalized organic nanoribbons on the Ag(110) surface. C-H bond activation and homo-coupling of the precursors is achieved upon thermal activation. The anisotropic substrate acts as an efficient template fostering the alignment of the nanoribbons, up to the full monolayer regime. The length of the nanoribbons can be sequentially increased by controlling the annealing temperature, from dimers to a maximum length of about 10 nm, limited by epitaxial stress. The different structures are characterized by room-temperature scanning tunnelling microscopy. Distinct signatures of the covalent coupling are measured with high-resolution electron energy loss spectroscopy, as supported by density functional theory calculations.


[Estimation of chemical fertilizer N-induced direct N2O emission from China agricultural fields in 1991-2000 based on GIS technology].
Referring to the definition of agricultural field N2O emission factor by the Intergovernmental Panel on Climate Change, the main controlling factors climate and cropping system were introduced to estimate the chemical fertilizer N-induced direct N2O emission from China agricultural fields in 1991-2000, and a spatial inventory with 10 km x 10 km resolution was developed by dint of GIS framework. The results indicated that there was an increasing trend in the annual direct N2O emission, due to the increasing input of chemical fertilizer N. The mean annual emission in 1990s was estimated to be 204 Gg N2O-N, ranging from 159 to 269 Gg N2O-N, and the lowest and the highest emission occurred in 1992 and 1998, respectively. The uncertainty of the estimation was quantified to be about 23%. The spatial distribution of N2O emission was characterized by higher flux in eastern China and lower flux in western China, which was mainly attributed to the application rate of chemical fertilizer N and precipitation.


BRAF mutations in papillary thyroid carcinoma.
Papillary thyroid carcinoma (PTC) is the most frequent malignant neoplasm of the thyroid originating from the thyroid follicular cell (TFC). Although the formation of PTC is believed to result from rearrangements of RET or TRK oncogenes or MET point mutations, these structural aberrations or point mutations do not correlate with the clinicopathological features of PTC and do not seem to be a useful prognostic marker of the disease. Therefore, further experiments should be carried out in order to find new practical clinical markers. Recently, oncogene BRAF has become a subject of great interest. The mutation of BRAF gene is characteristic for PTC and poorly differentiated and/or undifferentiated cancers derived from PTC. The occurrence of BRAF mutation has often been observed in various human tumours. The presence of mutation was confirmed in melanoma, colon cancer, gliomas and lung cancer. In the majority of cases, there is only one type of point mutation - V600E. The RAS/RAF/MEK/MAPK kinase pathway mediates the cellular response to mitogenic signals. BRAF gene mutation results in increased kinase activity, leading to excessive activation of the above mitogenic pathway and to uncontrolled proliferation of cancer cells. Some correlation was noticed between BRAF gene mutation and the clinical stage of the neoplastic disease in question. Preliminary investigations indicate that the presence of BRAF mutation might be a valuable diagnostic and prognostic marker of the disease. Further investigations could also bring further improvements into the therapeutic management of thyroid cancer. There are reports emphasizing the possibility of using the inhibitors of BRAF proteins in the treatment of PTC. Certainly, in order to confirm the diagnostic usefulness of this marker, further studies should be carried out.


High-resolution microscopy of lung and intrathoracic tumors.
Effective chemotherapy is available for many types of lung tumors; however, to select the most appropriate regimen, precise classification is essential. The most important differentiation is that between small cell and non-small cell anaplastic carcinoma. It is also important to distinguish mediastinal neoplasms and neoplasms metastatic to lung from primary lung tumors. Processing tissue in methacrylate and epoxy resins results in excellent preservation of histologic detail and allows for maximum resolution under the light microscope. In addition, histochemical and immunochemical procedures can be carried out in these preparations, allowing the pathologist to more precisely classify the various tumors.


Tapia's syndrome as an uncommon complication after cervical spine surgery with tracheostomy: a case report and literature review.
The aim of the present work is to present a rare case of Tapia's syndrome (hypoglossal and recurrent laryngeal nerve apraxia) following cervical spine surgery with tracheostomy. Clinical data were collected from patient's medical records. After uneventful cervical spine surgery with tracheostomy, the patient reported mild dysphagia and dysphonia. Clinical examination and electromyography confirmed unilateral hypoglossal and recurrent laryngeal disfunction, contralateral to surgical access. Neural damage was transitory and full functional recovery was achieved within 12 months. Tapia's syndrome can be a rare complication of cervical spine surgery with tracheostomy, due to multiple factors, including tracheostomy cuffed cannula and cervical spine position during surgery.


Hard work does not result in a decrease in meal quality: the case of a Japanese farming village.
Historically, when Japanese farmers engaged in hard labor, they were likely to increase their carbohydrate intake without increasing intake of other nutrients. After Japan's economic growth started in the 1960s, however, many kinds of food became available and affordable. We investigated whether farmers today have increased the nutrients in their diet in proper proportion to energy expenditures when they are engaged in farming work by comparing the quantity and quality of meals between farmers and other villagers within a small area of a farming village. The quantity of energy and other nutrients increased with farming work, but the amounts of each nutrient per unit of energy did not decrease with the increase in energy intake. The intake of each nutrient relative to the recommended dietary allowance for energy and each nutrient did not decrease with farming work either. It was concluded that the quality of meals of farmers does not decrease with the increasing energy intake for farming work when many kinds of food are available and affordable.


Expression of cortical and medullary thymic epithelial antigens in thymomas. An immunohistological study of 14 cases including a characterization of the lymphocytic compartment.
Four monoclonal antibodies against antigens expressed differentially by the normal thymus epithelium, which define the cortical, medullary and subcapsular compartments, were used for immunohistological characterization of the epithelial cells in 14 thymomas. Furthermore, thymoma-associated lymphocytes were studied with monoclonal antibodies directed against T-lymphocyte differentiation antigens (CD1a, CD3, T-cell antigen receptor). Only four of the 14 thymomas could be classified into either medullary or cortical type thymoma based on the immunophenotype of epithelial cells. Ten cases escaped immunophenotypical classification due to co-expression of medullary and cortical antigens by the tumour cells. This aberration from the normal phenotype might indicate the failure of differentiation of such tumours. The immunophenotype of the associated lymphocytes, on the other hand, made it possible to classify the tumours as cortical (5 cases), mixed (2) and medullary (3) thymomas. Four thymomas escaped this classification scheme due to the absence of lymphocytes (2) or to a hybrid immunophenotype (2). Nevertheless, thymocytes of cortical type clearly predominated and were seen in all thymomas with associated lymphocytes. This feature may constitute a good diagnostic tool in differential diagnosis since, in 28 mediastinal or extramediastinal metastasis of tumours not derived from thymic epithelium and associated with various numbers of lymphocytes, none of them were found to contain CD1a positive lymphocytes.


Assessment and risk prediction of frailty using texture-based muscle ultrasound image analysis and machine learning techniques.
The purpose of this study was to evaluate texture-based muscle ultrasound image analysis for the assessment and risk prediction of frailty phenotype. This retrospective study of prospectively acquired data included 101 participants who underwent ultrasound scanning of the anterior thigh. Participants were subdivided according to frailty phenotype and were followed up for two years. Primary and secondary outcome measures were death and comorbidity, respectively. Forty-three texture features were computed from the rectus femoris and the vastus intermedius muscles using statistical methods. Model performance was evaluated by computing the area under the receiver operating characteristic curve (AUC) while outcome prediction was evaluated using regression analysis. Models developed achieved a moderate to good AUC (0.67 ≤ AUC ≤ 0.79) for categorizing frailty. The stepwise multiple logistic regression analysis demonstrated that they correctly classified 70-87% of the cases. The models were associated with increased comorbidity (0.01 ≤ p ≤ 0.18) and were predictive of death for pre-frail and frail participants (0.001 ≤ p ≤ 0.016). In conclusion, texture analysis can be useful to identify frailty and assess risk prediction (i.e. mortality) using texture features extracted from muscle ultrasound images in combination with a machine learning approach.


[Labor environment and heatstroke].
The Ministry of Health, Labour and Welfare and the Heatstroke STUDY 2008 & 2010 regarding the characteristics of laborers who suffered and died from heatstroke demonstrated the involvement of more laborers who worked in construction, from July to August and at around 3 p.m. Also, more laborers who worked at around 11 a.m. got heatstroke, and there were more laborers who died from it within 1 week from starting to work. The results showed that the heat environment and the time and period when laborers started to be exposed to a hot environment adversely effect the development of heatstroke and subsequent heatstroke-related death. It is important to estimate and take measures against a hot environment and to make time to be acclimated to a hot environment.


Practice patterns of canadian physiotherapists mobilizing patients with external ventricular drains.
To describe current mobilization practices of Canadian physiotherapists when treating patients with external ventricular drains (EVDs). A quantitative, descriptive, cross-sectional study design using an online questionnaire via SurveyMonkey. An email invitation and questionnaire link was distributed in March 2010 to physiotherapists currently working with this patient population in Neurosurgical Centres across Canada. Respondents were 25 physiotherapists (21 full-time, 2 part-time, and 2 who did not disclose work status) working in 5 different provinces who treated ≥1 patient/month with an EVD (n=9). Slightly more than half of respondents had ≤10 years' clinical physiotherapy experience (n=14); the remainder had >10 years' experience (n=11). The majority of respondents indicated that they felt comfortable mobilizing patients with EVDs (n =19) and that it was safe to do so (n=20). Clinical experience (n=23) and safety concerns (n=25) were most commonly cited as guiding practice. More experienced physiotherapists were more likely to use out-of-bed mobilization practices. Regardless of experience, the majority of physiotherapists (20/25) ranked intracranial pressure (ICP) as the most important factor and saturation of oxygen (Spo2) as the least important factor to consider before mobilization. Canadian physiotherapists are mobilizing patients with EVDs, and the intensity level of their mobilization practices appears to be related to their experience level. Data from the current study may be used in developing future best-practice guidelines for the mobilization of patients with EVDs.


Survival and prognostic factors in thyroid carcinoma.
A multivariate analysis of prognostic factors and survival was carried out in a series of 200 patients with thyroid carcinoma. The cumulative survival rate corrected for intercurrent deaths was higher for papillary carcinoma than for follicular carcinoma both at 5 years (92% vs 74%) and at ten years (87% vs 66%) after the diagnosis. Seventeen of the eighteen patients with anaplastic carcinoma died within 24 months after the diagnosis. The most important independent prognostic factor in patients with papillary or follicular carcinoma, by multivariate analysis, was age at time of diagnosis, followed by tumor penetration beyond the thyroid capsule and follicular histologic type. When different types of treatment were included in the analysis, age at diagnosis still remained the most important prognostic factor. Misdiagnosed intercurrent deaths in the elderly did not explain the negative effect of age on survival.


Integration of pan-cancer multi-omics data for novel mixed subgroup identification using machine learning methods.
Cancer is a heterogeneous disease, and patients with tumors from different organs can share similar epigenetic and genetic alterations. Therefore, it is crucial to identify the novel subgroups of patients with similar molecular characteristics. It is possible to propose a better treatment strategy when the heterogeneity of the patient is accounted for during subgroup identification, irrespective of the tissue of origin. This work proposes a machine learning (ML) based pipeline for subgroup identification in pan-cancer. Here, mRNA, miRNA, DNA methylation, and protein expression features from pan-cancer samples were concatenated and non-linearly projected to a lower dimension using an ML algorithm. This data was then clustered to identify multi-omics-based novel subgroups. The clinical characterization of these ML subgroups indicated significant differences in overall survival (OS) and disease-free survival (DFS) (p-value<0.0001). The subgroups formed by the patients from different tumors shared similar molecular alterations in terms of immune microenvironment, mutation profile, and enriched pathways. Further, decision-level and feature-level fused classification models were built to identify the novel subgroups for unseen samples. Additionally, the classification models were used to obtain the class labels for the validation samples, and the molecular characteristics were verified. To summarize, this work identified novel ML subgroups using multi-omics data and showed that the patients with different tumor types could be similar molecularly. We also proposed and validated the classification models for subgroup identification. The proposed classification models can be used to identify the novel multi-omics subgroups, and the molecular characteristics of each subgroup can be used to design appropriate treatment regimen.


The precision of the hominid timescale estimated by relaxed clock methods.
The chronological scenario of the evolution of hominoid primates has been thoroughly investigated since the advent of the molecular clock hypothesis. With the availability of genomic sequences for all hominid genera and other anthropoids, we may have reached the point at which the information from sequence data alone will not provide further evidence for the inference of the hominid evolution timescale. To verify this conjecture, we have compiled a genomic data set for all of the anthropoid genera. Our estimate places the Homo/Pan divergence at approximately 7.4 Ma, the Gorilla lineage divergence at approximately 9.7 Ma, the basal Hominidae divergence at 18.1 Ma and the basal Hominoidea divergence at 20.6 Ma. By inferring the theoretical limit distribution of posterior densities under a Bayesian framework, we show that it is unlikely that lengthier alignments or the availability of new genomic sequences will provide additional information to reduce the uncertainty associated with the divergence time estimates of the four hominid genera. A reduction of this uncertainty will be achieved only by the inclusion of more informative calibration priors.


Terry's Nails: A Sign of Systemic Disease.
Terry's nails are a type of apparent leukonychia, characterized by ground glass opacification of nearly the entire nail, obliteration of the lunula, and a narrow band of normal, pink nail bed at the distal border. The aim of this study is to guide clinical practice by reviewing all of the data concerning Terry's nail that have become available since the original description by Terry in 1954, with particular reference to all clinical features, associated medical conditions, pathogenesis, and necessary workup. PubMed was searched using the keywords "leukonychia" and "Terry nails." Although the abnormality can occur with normal aging, Terry's nails can also be an indication of an underlying medical condition, most notably, cirrhosis, chronic renal failure, and congestive heart failure. A change in nail bed vascularity, secondary to overgrowth of connective tissue, is thought to be responsible, with nail bed biopsy revealing telangiectasias in the distal band. The differential diagnosis for Terry's nails includes half-and-half nails (Lindsay's nails), Muehrcke's nails, and true leukonychia totalis/partialis. Having the ability to delineate these nail findings can be a valuable tool in clinical practice as each entity is associated with a different set of systemic conditions. Terry's nails highlight the intimate connection between nail changes and systemic disease as well as the importance of thorough nail inspection with every physical examination.


The predictive value of serum lipids for eye metastases in male nasopharyngeal carcinoma patients.
Nasopharyngeal carcinoma (NPC) is a tumor that is commonly found in southern China. NPC has several risk factors, such as infection with the Epstein-Barr virus. However, we know little about the risk factors for eye metastasis (EM) in male patients with NPC. Serum lipids are well recognized as risk factors for cardiovascular disease, and recent studies show that they also have a relationship with the development of NPC. We designed the present study to determine whether they were relevant with the development of EM in male NPC patients by detecting the levels of several serum lipids. A total of 1140 male patients with NPC were enrolled in this retrospective study and we divided them into two groups: the metastasis (EM) group and non-eye metastasis (NEM) group. A variety of serum lipids between the two groups were tested and compared. There were statistical differences in the levels of serum TG and TC between these two groups. Binary logistic regression showed that TG and TC were independent risk factors for EM in male NPC patients with P=0.004 and P<0.001, respectively. The area under the curve of TG and TC were 0.764 and 0.681, respectively, using cutoff values of 0.975 and 3.425 mmol/l, respectively. We found that TG had higher sensitivity and specificity values with 87.5% and 62.7%, respectively, than TC which were 50.0% and 87.2%. TG and TC are potential risk factors for eye metastases in male NPC patients.


Pseudotumor cerebri and pregnancy.
We reviewed 11 pregnancies complicated by pseudotumor cerebri over a 6-year period for an incidence of approximately 1 in 870 births. No pregnancy was adversely affected, but symptoms of pseudotumor increased in 9 of 11 pregnancies. All patients were managed medically, 9 of 11 with analgesics and diuretics. Two cases required steroid therapy.


Long Head of Triceps Tendon Transfer for Agenesis of Biceps and Brachialis: Two Cases.
Congenital lack of elbow flexion results in significant disability and may be seen in conjunction with syndromes, plexopathies, neuromuscular disorders, or as an isolated muscular agenesis of elbow flexors. There are many tendon transfer options to address this issue, but there is a lack of data on the functional results in the pediatric population. In this series, we present 1 patient with isolated muscular agenesis of the biceps and brachialis musculotendinous units and another with this same muscular agenesis in the setting of arthrogryposis. They were treated with anterior ulnar nerve transposition and transfer of the long head of triceps tendon around 2 years of age resulting in functional elbow flexion in both patients.


Genetic determinants involved in p-aminosalicylic acid resistance in clinical isolates from tuberculosis patients in northern China from 2006 to 2012.
p-Aminosalicylic acid (PAS) is an important compound for treating multidrug-resistant tuberculosis (TB). Previous studies showed that thyA mutations are often related to PAS resistance in clinical isolates. We performed a systematic analysis of isolate genotypes and detected mutations in three folate pathway genes (folC, thyA, and ribD) in 61.1% (127/208) of PAS-resistant isolates, including 11 double mutants. This result expands our knowledge about the distribution and frequency of mutations related to PAS resistance in mycobacterial clinical isolates.


Correlations between radiographic, clinical and mobility parameters after loading of oral implants with fixed partial dentures. A 2-year longitudinal study.
The aim of present study was to correlate the changes in the peri-implant tissues occurring after functional loading of non-submerged titanium implants and assessed by radiographic, clinical and mobility measurements. 11 patients with distal extension situations received 18 implants of the ITI Dental Implant System. After a healing period of 3 months, the suprastructures were fabricated and seated 5 months post-surgically. For the assessment of peri-implant bone changes, standardized vertical bitewing radiographs with reproducible exposure geometry were evaluated using computer assisted densitometric image analyses (CADIA) and bone height measurements. Since the radiographic evaluations were performed at mesial and distal sites only, the clinical parameters from these implant aspects were included in the analysis. Clinical periodontal parameters modified for the use around implants were obtained, damping characteristics were expressed as Periotest readings and standardized radiographs were obtained at 1, 3, 6, 12 and 24 months after loading. In addition, radiographs were also taken at the start of functional loading. The data obtained from this small sample of implants demonstrated a wide range of different tissue alterations when using radiographic, clinical and mobility assessments. The parameters of probing attachment level (PAL) in combination with radiographic parameters obtained at 1, 3, and 6 months after loading were good predictors for the peri-implant tissue status at 2 years. This was shown by means of multiple stepwise regression analyses. Mobility measurements did not reveal valuable predictive information with the statistical models applied. Assessments of probing attachment levels using periodontal probes rendered information on peri-implant tissue alterations, which were closely correlated to the radiographically measurable peri-implant bone changes.


BRG1 attenuates colonic inflammation and tumorigenesis through autophagy-dependent oxidative stress sequestration.
Autophagy is a central component of integrated stress responses that influences many inflammatory diseases, including inflammatory bowel disease (IBD) and colorectal cancer (CRC). While the core machinery is known, the molecular basis of the epigenetic regulation of autophagy and its role in colon inflammation remain largely undefined. Here, we report that BRG1, an ATPase subunit of the SWI/SNF chromatin remodeling complex, is required for the homeostatic maintenance of intestinal epithelial cells (IECs) to prevent the inflammation and tumorigenesis. BRG1 emerges as a key regulator that directly governs the transcription of Atg16l1, Ambra1, Atg7 and Wipi2, which are important for autophagosome biogenesis. Defective autophagy in BRG1-deficient IECs results in excess reactive oxygen species (ROS), which leads to the defects in barrier integrity. Together, our results establish that BRG1 may represent an autophagy checkpoint that is pathogenetically linked to colitis and is therefore likely a potential therapeutic target for disease intervention.


CD86 +1057 G/A polymorphism and the risk of colorectal cancer.
CD86 (B7-2), one of the costimulatory molecules on antigen-presenting cells, plays essential roles not only in autoimmunity and transplantation but also in tumor immunity. The purpose of this study was to investigate whether CD86 gene polymorphism was involved in predisposing an individual to colorectal cancer (CRC). The CD86 +1057 G/A polymorphism was genotyped by performing polymerase chain reaction-restriction fragment length polymorphism in 273 patients with CRC and 292 healthy controls. There were significant differences in the genotype and allele distribution of +1057 G/A polymorphism of the CD86 gene between cases and controls. The +1057 AA genotype was associated with a significantly increased risk of CRC when compared with the GG genotype (odds ratio [OR] = 2.16; 95% confidence interval [CI], 1.31-3.58). Using the G allele as a reference, a significant correlation was detected between the presence of the A allele and a risk of developing CRC (OR = 1.42; 95% CI, 1.12-1.80). Interestingly, the A allele in female patients with CRC was significantly higher than that in male patients after stratified analysis (OR = 1.49; 95% CI, 1.04-2.14). These data suggest that CD86 +1057G/A polymorphism may contribute to genetic susceptibility to CRC in a Chinese population.


A Global Meta-Analysis of the Impacts of Forest Fragmentation on Biotic Mutualisms and Antagonisms.
Forest fragmentation is a grave threat to biodiversity. Forests are becoming increasingly fragmented with more than 70% now < 1 km from forest edge. While much is known about the effects of forest fragmentation on individual species, much less is understood about its effects on species interactions. In 2014, a meta-analysis by Magrach et al. assessed the impacts of forest fragmentation on different species interactions, across 82 studies. We expand on their findings by pooling their original data with new data published in the last 10 years, yielding 104 studies and 168 effect sizes. We also compare the new set of publications to the old set to evaluate potential changes in species interactions over time given the global increase in fragmentation rates. Our results confirm the original findings that mutualisms are more negatively impacted by forest fragmentation than antagonisms (p < 0.0001). Additionally, we found that edge effects, fragment size, and degradation negatively impact mutualisms, but not antagonisms; a different finding from the original meta-analysis. We determined that parasitic interactions are stronger with decreasing fragment size (p < 0.0001) - an intriguing result at variance with earlier studies. When data from old and new publications were compared, we found a more negative mean effect size of forest fragmentation on mutualisms. While research is still limited for some interactions, we identified an important scientific trend: current research focuses more on antagonisms. We conclude that forest fragmentation disrupts important species interactions and that this disruption has increased over time. This article is protected by copyright. All rights reserved.


Phencyclidine administration during neurodevelopment alters network activity in prefrontal cortex and hippocampus in adult rats.
Symptoms of schizophrenia have been linked to insults during neurodevelopment such as NMDA receptor (NMDAR) antagonist exposure. In animal models, this leads to schizophrenia-like behavioral symptoms as well as molecular and functional changes within hippocampal and prefrontal regions. The aim of this study was to determine how administration of the NMDAR antagonist phencyclidine (PCP) during neurodevelopment affects functional network activity within the hippocampus and medial prefrontal cortex (mPFC). We recorded field potentials in vivo after electrical brain stem stimulation and observed a suppression of evoked theta power in ventral hippocampus, while evoked gamma power in mPFC was enhanced in rats administered with PCP neonatally. In addition, increased gamma synchrony elicited by acute administration of the NMDAR antagonist MK-801 was exaggerated in neonatal PCP animals. These data suggest that NMDAR antagonist exposure during brain development alters functional networks within hippocampus and mPFC possibly contributing to the reported behavioral symptoms of this animal model of schizophrenia.NEW & NOTEWORTHY We show that insults with a NMDA receptor antagonist during neurodevelopment lead to suppressed evoked theta oscillations in ventral hippocampus in adult rats, while evoked gamma oscillations are enhanced and hypersensitive to an acute challenge with a NMDA receptor antagonist in prefrontal cortex. These observations reveal the significance of neurodevelopmental disturbances in the evolvement of schizophrenia-like symptoms and contribute to the understanding of the functional deficits underlying aberrant behavior in this disease.


Effect of Children's Drinks on Color Stability of Different Dental Composites: An in vitro Study.
To assess the effect of four different children's drinks on color stability of resin dental composites. A total of one hundred and twenty specimens were prepared from Grandio SO, Filtek Z350 XT and Filtek Z250 XT (forty specimens each). Specimens were thermocycled, then each group was further subdivided into four subgroups (n=10) according to the immersion media which were chocolate milk, mango juice, orange fizzy drink, and water (control). The initial color parameters of each specimen were recorded before immersion (baseline) and color change values were recorded three and seven days after immersion in each solution using a digital spectrophotometer. Atomic force microscope was used to measure the surface roughness in randomly selected samples after one week immersion in children's drinks. All the children's drinks produced color changes in the examined resin dental composites, yet there was no statistical significant difference between the effects of tested drinks on the color changes (mean ΔE) of the three different dental composites (P>0.05). All tested children's drinks caused clinically unacceptable color changes of the tested resin dental composites. Immersion in chocolate milk and orange fizzy led to the highest color changes in the tested resin dental composites.


Proline-specific dipeptidyl aminopeptidase from Flavobacterium meningosepticum.
A proline-specific dipeptidyl aminopeptidase was highly purified from cell-free extract of Flavobacterium meningosepticum by a series of column chromatographies on DEAE-Sephadex A-50, Sephadex G-150, hydroxyapatite, and a second gel filtration on Sephadex G-150. The enzyme was most active at pH 7.4-7.8 for both Gly-Pro-beta-naphthylamide (Gly-Pro-2-NNap) and Gly-Pro-p-nitroanilide (Gly-Pro-pNA) and was stable between pH 7 and 9.5. The enzyme was markedly inhibited by diisopropylphosphofluoridate (DFP) and mercury ion but not by sulfhydryl-blocking reagents and metal chelators. The molecular weight of the enzyme was about 160,000 as judged by the gel filtration method and the subunit molecular weight was estimated to be 75,000 by sodium dodecyl sulfate (SDS)-gel electrophoresis, suggesting a dimeric form of the native enzyme. The isoelectric point was at pH 9.5. The enzyme hydrolyzed peptides and peptide amides at the carboxyl side of a proline residue penultimate to the amino-terminal amino acid, as did post-proline dipeptidyl aminopeptidases from various mammals. However, antiserum raised against post-proline dipeptidyl aminopeptidase from porcine kidney did not cross-react with the Flavobacterium dipeptidyl aminopeptidase.


Surgery for pediatric craniopharyngiomas: is less more?
Surgery for craniopharyngiomas, especially in childhood and adolescence, has evolved from an era of aggressive strategies - with the primary goal of gross total removal and accepting an impaired functional outcome - to a more individually tailored therapy that avoids immediate treatment-related and long-term morbidity. Modern imaging techniques and a wider understanding of hypothalamic risk factors have led to surgical strategies adapted to the localization of these inhomogenously grown pathologies. Whereas purely infradiaphragmatic as well as supradiaphragmatic/infrachiasmatic tumors have a favorably surgical outcome with higher gross total resection rates in experienced hands, lesions within the third ventricle extending beyond the mammillary bodies remain a problem. The same is valid for lesions beyond 3 cm in diameter, more or less independent of their localization. Aside from the traditional microscopic approach via the subfrontal or pterional craniotomy, transsphenoidal approaches and other minimal invasive surgical methods, e.g., catheter implantation into cystic formations of the tumor have become popular. Radiotherapy, with its risks and limitations, can effectively be added to avoid recurrences. Nowadays, surgery as part of an interdisciplinary treatment strategy is still the typical first choice. However, taking the patient's long-term prognosis into considertaion, the surgical complication rates have to be minimized.


Characterization of the release and biological significance of cell-free DNA from breast cancer cell lines.
In breast cancer, cell-free DNA (cfDNA) has been proven to be a diagnostic and prognostic biomarker. However, there have been few studies on the origin and biological significance of cfDNA. In this study, we assessed the release pattern of cfDNA from breast cancer cell lines under different culture conditions and investigated the biological significance of cfDNA. The cfDNA concentration increased rapidly (6 h) after passage, decreased gradually, and was then maintained at a relatively stable level after 24 h. In addition, the cfDNA concentration did not correlate with the amount of apoptotic and necrotic cells. Interestingly, if more cells were in the G1 phase, more cfDNA was detected (p < 0.01) and the cfDNA concentration correlated positively with the percent of cells in the G1 phase (p < 0.05). We observed that cells could release cfDNA actively, but not exclusively, via exosomes. Furthermore, we showed that cfDNA could stimulate hormone receptor-positive breast cancer cell proliferation by activating the TLR9-NF-κB-cyclin D1 pathway. In conclusion, cfDNA is released from breast cancer mainly by active secretion, and cfDNA could stimulate proliferation of breast cancer cells.


[Chronic subdural hematoma: a review of the literature. Part 1].
The first part of this publication is a review of the literature on the history, etiopathogenesis, clinical signs, and diagnosis of chronic subdural hematoma (CSDH). The incidence rate of CSDH is 2-11 cases per 100000 inhabitants. In spite of many anatomopathologic and biochemical studies, the pathomechanism of CSDH has not been fully explained. Although head computed tomography is the method of choice for the diagnosis of CSDH, magnetic resonance imaging can provide much more structural information on the hematoma. The pathophysiology of mental changes and hemiparesis in CSDH remains unclear. However, disturbances of cerebral haemodynamics seem to play a major role.


Autologous scalp skin grafting to treat toxic epidermal necrolysis in a patient with a large skin injury: A case report.
Toxic epidermal necrolysis (TEN) is often associated with skin wounds affecting large areas. Healing of this type of wound is difficult because of pressure, infection and other factors. It can increase the length of hospital stay and result in wound sepsis and even death. A 49-year-old woman developed a skin lesion covering 80% of the total body surface area after using a kind of Chinese medicinal ointment on a burn wound on her back; she developed life-threatening wound sepsis and septic shock. Methicillin-resistant Staphylococcus aureus, carbapenem-resistant Acinetobacter baumannii, carbapenem-resistant Pseudomonas aeruginosa and other bacteria were cultured from wound tissue, deep venous catheter and blood samples. Imipenem cilastatin sodium, tigecycline and teicoplanin were used for anti-infection therapy. Finally, the patient was transferred to the burn department because of severe wound sepsis. In the burn intensive care unit, pain-free dressing changes and autologous scalp skin grafting were performed to heal the wound in addition to reasonable and effective antibacterial treatment according to microbial susceptibility test results. After three operations within 2 wk, the wound healed and sepsis resolved. TEN patients with large areas of skin injury may develop wound infection and life-threatening wound sepsis. Autologous scalp skin grafting may be beneficial for rapid wound healing and reducing the risk of sepsis in TEN patients, and it leaves no scar at the donor site.


COVID-19-induced cardiovascular damage differs from other prevalent viruses.
Viral infections persist globally, among all ages, gender, and ethnicity. Of particular importance is COVID-19, associated with asymptomatic to severe symptoms, including complications/mortality. Cardiovascular disease (CVD) involves heart and blood vessel disorders including coronary heart disease, cerebrovascular disease, peripheral artery disease, thrombosis, and more. CVD associated with severe COVID-19 includes heart failure, coronary artery disease, cardiomyopathy, hypertension, and cerebrovascular disease/stroke. Data were acquired from PubMed, Google Scholar, Centers for Disease Prevention and Control, and Lexi-Comp using the search terms "COVID-19 and cardiovascular pathology;" "COVID-19 induced CVD;" "Viral infection induced CVD;" and "Viral infection induced heart damage." COVID-19-induced CVD mechanisms include direct viral entry, inflammation, cytokine storm, hypoxia, interferon-mediated immune response, plaque destabilization, stress, and drug-induced causes. Other viral pathologies causing CVD include atherosclerosis, inflammation, cytokine storm, and plaque destabilization. Individual parameters, such as old age, males, and higher body mass index (BMI), are more likely to experience viral-associated complications, possibly explained by patient risk factors or comorbidities. Populations at higher risk include older males with an elevated BMI. Viral mechanisms associated with CVD are similar but differ in disease severity, potentially explained by diverse cytokine profiles where COVID-19 activates different types at higher quantities.


Aspidoras mephisto, new species: The first troglobitic Callichthyidae (Teleostei: Siluriformes) from South America.
Aspidoras mephisto n. sp. is described from the Anésio-Russão cave system, upper Tocantins River basin, Goiás, Brazil. The species can be readily distinguished from its congeners by troglomorphic features and also by presenting the following combination of features: infraorbital 1 generally with well-developed ventral laminar; or moderately developed; poorly-developed serrations on posterior margin of pectoral spine; nuchal plate not externally visible; dorsal fin, even in conspicuously colored specimens, with only dark brown or black chromatophores concentrated on rays, forming spots in some specimens; membranes hyaline; or sparse dark brown or black chromatophores on membranes, not forming any conspicuous pattern; and inner laminar expansion of infraorbital 1 moderately developed. Information about its habitat, ecology, behaviour and conservation status are provided and also a brief description of the juvenile stage.


Size- and distance-dependent nanoparticle surface-energy transfer (NSET) method for selective sensing of hepatitis C virus RNA.
We report size- and distance-dependent surface-energy transfer (SET) properties of gold nanoparticles for recognizing hepatitis C virus (HCV) RNA sequence sensitively and selectively (single-base mutations) in a homogeneous format. We have demonstrated that quenching efficiency increases by three orders of magnitude, as the particle size increases from 5 to 70 nm. Due to this extraordinarily high K(SV), nanoparticle SET (NSET) detection limit can be as low as 300 fM concentration of RNA, depending on the size of gold nanoparticle. We have shown that the distance-dependent quenching efficiency is highly dependent on the particle size and the distance at which the energy-transfer efficiency is 50 %, ranges all the way from 8 nm, which is very close to the accessible distance of conventional Förster resonance energy transfer (FRET), to about 40 nm by choosing gold nanoparticles of different diameters. Our result points out that dipole-to-metal-particle energy transfer and NSET models provide a better description of the distance dependence of the quenching efficiencies for 8 nm gold nanoparticle, but agreement is poor for 40 and 70 nm gold nanoparticles, for which the measured values were always larger than the predicted ones.


The Royal College of Nursing's quest to improve recruitment.
Emeritus Professor Alan Glasper, from the University of Southampton, discusses a recent report by the Royal College of Nursing calling for the Government to change the system of funding for nurse education.


Working hours of obstetrics and gynaecology trainees in Australia and New Zealand.
The importance of doctors' working hours has gained significant attention with evidence suggesting long hours and fatigue may compromise the safety and wellbeing of both patients and doctors. This study aims to quantify the working hours of The Royal Australian and New Zealand College of Obstetricians and Gynaecologists (RANZCOG) specialist trainees in order to better inform discussions of working hours and safety within our region. An anonymous, online survey of RANZCOG trainees was conducted. Demographic data were collected. The primary outcomes were: hours per week at work and hours per week on-call. Secondary outcomes included the frequency of long days (>12 h) and 24-h shifts, time spent studying, staff shortages and opinions regarding current rostering. Response rate was 49.5% (n = 259). Full-time trainees worked an average of 53.1 ± 10.0 h/week, with 11.6% working on-call. Long-day shifts were reported by 85.8% of respondents, with an average length of 14.2 h. Fifteen percent reported working 24-h shifts, with a median duration of uninterrupted sleep during this shift being 1-2 h. Trainees in New Zealand worked 7.0 h/week more than Australian trainees (P ≤0.001), but reported less on-call (P = 0.021). Trainees in Western Australia were more likely to work on-call (P ≤0.001) and 24-h shifts (P ≤0.001). While 53.1 h/week at work is similar to the average Australian hospital doctor, high rates of long days and 24-h shifts with minimal sleep were reported by RANZCOG trainees in this survey.


Anxiety and actualization: a reconceptualization.
In line with Dabrowki's theory of Positive Disintegration, deGrace recently reported no significant difference in terms of anxiety level between groups of actualized and nonactualized Ss. Several methodological and theoretical flaws noted in the deGrace study led the present authors to hypothesize that actualized Ss would score significantly lower than nonactualized Ss on separate but conceptually related measures of manifest or neurotic anxiety. Ss (83 females and 42 males) were administered the Personal Orientation Inventory, the IPAT Anxiety Scale, and the Taylor Manifest Anxiety Scale. The results, which substantiate the hypothesis that levels of actualization and anxiety are correlated negatively, are discussed in relation to the conceptual distinction between debilitating and facilitating anxiety and their respective effects on psychological growth.


HLA tissue typing and chronic vulval dystrophy.
Tissue typing was performed on 25 patients who attended the Royal Victoria Hospital with chronic vulval dystrophy (CVD). Age-matched control groups who had pernicious anaemia only and achlorhydria only were also tissue typed as these conditions had been found more frequently in our patients with CVD. When these three groups were compared with age-matched control groups of blood donors and patients with gynaecological disorders other than CVD, no specific tissue type was found in patients with CVD nor in those with pernicious anaemia or achlorhydria only.


Eveningness among late adolescent males predicts neural reactivity to reward and alcohol dependence 2 years later.
Eveningness, a preference for later sleep-wake timing, is linked to altered reward function, which may explain a consistent association with substance abuse. Notably, the extant literature rests largely on cross-sectional data, yet both eveningness and reward function show developmental changes. We examined whether circadian preference during late adolescence predicted the neural response to reward 2 years later. A sample of 93 males reported circadian preference and completed a monetary reward fMRI paradigm at ages 20 and 22. Primary analyses examined longitudinal paths from circadian preference to medial prefrontal cortex (mPFC) and ventral striatal (VS) reward responses. We also explored whether reward responses mediated longitudinal associations between circadian preference and alcohol dependence, frequency of alcohol use, and/or frequency of cannabis use. Age 20 eveningness was positively associated with age 22 mPFC and VS responses to win, but not associated with age 22 reactivity to reward anticipation. Age 20 eveningness was indirectly related to age 22 alcohol dependence via age 22 mPFC response to win. Our findings provide novel evidence that altered reward-related brain function could underlie associations between eveningness and alcohol use problems. Eveningness may be an under-recognized but modifiable risk factor for reward-related problems such as mood and substance use disorders.


Using data envelopment analysis and the bootstrap method to evaluate organ transplantation efficiency in Brazil.
Brazil has the most extensive public program for organ transplantation in the world, and the Brazilian National Health System (SUS) provides full coverage of all costs involved in organ donation, transplants, and post-transplant. Despite the relevance of the subject and the shortage of organs for transplants, transplantation process efficiency assessments are still uncommon in Brazil and abroad. This study aims to evaluate the efficiency of the Brazilian states and the Federal District in transforming potential organ donors into actual donations. We applied data envelopment analysis (DEA) in conjunction with the bootstrap technique, using organ transplantation data from 2018. The bootstrap methods applied (bootstrap technique, the bootstrap-biased scores of efficiency, and the bootstrap bias-corrected scores of efficiency) allow to obtain a confidence interval for DEA scores and provide greater robustness to studies based on DEA methodology. The bootstrap bias-corrected model indicates that there is significant room for improvement in terms of converting potential donors into actual donors. The mean corrected score is 0.55, signalizing that altogether the Brazilian states could maximize in 45% the number of transplanted organs without necessarily increasing the pool of potential donors. The study provides insights into the Brazilian processes of organ donation and transplantation, helping to identify locations in need of resource allocation improvements. Given the scarcity of studies with a joint application of DEA and bootstrap techniques in this crucial health activity, we also intend to methodologically contribute to this type of benchmark analysis, emphasizing the importance of considering measurement errors, randomness, and bias at DEA models.


Antitumor agents. 16. Steroidal alpha-methylene-gamma-lactones.
Several novel steroidal alpha-methylene-gamma-lactones and related derivatives have been synthesized as potential steroid alkylating antitumor agents. The synthesis of these compounds involved the convenient Reformatsky-type reaction between ethyl-alpha-(bromomethyl)acrylate and the proper steroidal ketones. In vitro assay for the cytotoxicity of these compounds against the growth of tissue culture cells originating from human epidermoid carcinoma of the larynx (H.Ep.-2) has shown significant activity. Cytotoxicity was improved at least sixfold with the introduction of lipophilic steroidal character. Preliminary in vivo tumor assay also indicated that these compounds were active against Walker 256 carcinosarcoma in rats and were inactive against both L1210 lymphoid leukemia and Ehrlich ascites carcinoma in mice. However, the simple alpha-methylene-beta,beta-dicarbethoxy-gamma-butyrolactone significantly inhibited Ehrlich ascites tumor growth.


LED dynamic electro-optical responses and light-fidelity-application optimization.
Commercial light-emitting diodes (LEDs) from different manufacturers were studied by means of impedance measurements in the frequency range between 75 kHz and 10 MHz. Electrical characteristics of these LEDs, such as impedance and resistance, were proven to be strongly influenced by the applied frequencies, the bias values, and the alternating-signal amplitudes. Through these measurements, a specific bias value, which later could be of great importance, was pointed out. Coupled with the optical signal-to-noise ratio measurements, this frequency-, bias-, and alternating-signal-amplitude-dependent impedance shows a close correlation between optical and electrical responses of LEDs, which turns out to be useful for visible light communication. Hence, a new and simple method of light-fidelity optimization through impedance measurements is proposed in this article.


Finnish patients with inflammatory bowel disease have fewer symptoms and are more satisfied with their treatment than patients in the previous European survey.
Symptoms associated with inflammatory bowel diseases (IBD) have a negative impact on quality of life. The purpose of this study was to assess the quality of life in a large group of Finnish IBD patients and to compare it with that observed in a recent survey covering several other European countries. The European Federation of Crohn's and Ulcerative Colitis Associations (EFCCA) questionnaire, comprising questions about IBD symptoms, diagnosis, therapy, extraintestinal manifestations and their impact on patients' quality of life, was sent to 3852 members of the Finnish Crohn and Colitis Association. The response rate was 63%. IBD was diagnosed by a specialist in over 96% of cases and 94% of patients were continuously followed-up by a specialist. Fifty-eight percent of the patients had had IBD symptoms for over a year before consulting a specialist. The frequency of symptoms was lower in the Finnish patients and 93% of patients were satisfied with their current treatment compared with 76% in the European survey. For Crohn's disease, the rate of surgery was lower than that in the European survey (43% versus 52%). The patients reported improved quality of life after surgery, but 67% of patients with Crohn's disease and 34% with ulcerative colitis reported recurrence of symptoms. Comorbidity with ankylosing spondylitis was 22 times more common than in the general Finnish population and 49% of the patients suffered from joint pain. Finnish IBD patients are more satisfied with their treatment than those studied in the European survey. In Finland, gastroenterologists are usually responsible for the care, but the delay before the diagnosis remains long.


Mutation, Chemoprofiling, Dereplication, and Isolation of Natural Products from Penicillium oxalicum.
Diethyl sulfate (DES)-based chemical mutagenesis was applied on different fungal strains with the aim of diversifying the secondary metabolites. The mutant strain (VRE-MT1) of Penicillium oxalicum was subjected to dereplication (LCMS-based) and isolation of natural products, resulting in obtaining 10 molecules of bioactive potential. Metabolites, viz. tuckolide, methylpenicinoline, 2-acetyl-3,5-dihydroxy-4,6-dimethylbenzeneacetic acid, penicillixanthone A, brefeldin A 7-ketone, and antibiotic FD 549, were observed for the first time from P. oxalicum. The results of antimicrobial activity reveal that the compounds N-[2-(4-hydroxyphenyl)ethenyl]formamide, methylpenicinoline, and penipanoid A have potent antibacterial activity against Bacillus subtilis (ATCC 6633) with minimum inhibitory concentration (MIC) values of 16, 64, and 16 μM, respectively, and the compounds N-[2-(4-hydroxyphenyl)ethenyl]formamide, methylpenicinoline, and penipanoid A were found active against Escherichia coli (ATCC 25922), with MIC values of 16, 64, and 16 μM, respectively. Also, the metabolites N-[2-(4-hydroxyphenyl)ethenyl]formamide and tuckolide showed effective antioxidant activity in 2,2-diphenyl-1-picrylhydrazyl and 2,2'-azino-bis(3-ethylbenzothiazoline)-6-sulfonic acid scavenging assays. The mutant VRE-MT1 was found to have 8.34 times higher quantity of N-[2-(4-hydroxyphenyl)ethenyl]formamide as compared to the mother strain. The DES-based mutagenesis strategy has been found to be a potent tool to diversify the secondary metabolites in fungi.


Expression levels and clinical significance of hepsin and HMGB1 proteins in cervical carcinoma.
This study assessed the hypothesis that the protein levels of high mobility group box 1 (HMGB1) and hepsin can be used as markers for diagnosis and prognosis in cervical carcinoma. Seventy patients with cervical cancer who were hospitalized in Xuzhou Central Hospital from May 2008 to June 2010 and underwent surgical treatment were selected for the observation group. At the same time, 20 patients with cervical benign lesions who underwent tumor stripping or accessory resection were selected for the control group. Immunohistochemical (SP) detection methods were used to detect hepsin and HMGB1 protein levels in tissues. The positive rates of HMGB1 cells in normal, paracancerous and cancerous cervical tissues were 5.0% (1/20), 22.9% (16/70) and 95.7% (67/70) (F=24.581, P=0.001) respectively. The positive rates of hepsin in normal, paracancerous and cancerous cervical tissues were respectively 10% (2/20), 61% (43/70) and 90% (63/70) (F=11.538, P=0.001). The HMGB1 expression level was related to the degree of tumor differentiation, lymph node metastasis and TNM stage (P<0.05). While the level of hepsin expression was related to the degree of tumor differentiation, invasion depth, lymph node metastasis and TNM stage (P<0.05). Furthermore, a positive correlation between the levels of hepsin and HMGB1 was found (r=15.27, P<0.05). The overall 5-year survival rates of patients with high expression of HMGB1 (+++) and low expression of HMGB1 (+ to ++) were respectively 51.2 and 29.2% (HR=11.637, 95% CI=4.351-38.213; P=0.002). The overall 5-year survival rates of patients with high hepsin expression (+++) and low hepsin expression (+ to ++) were respectively 41.3 and 35.3% (HR=10.143, 95% CI=4.285-33.275; P=0.006). Based on our results, the higher the levels of expression of hepsin and HMGB1 in tissues the higher the degree of invasiveness of the cervical cancers, and the worse the prognoses for the patient.


Octreotide inhibits liver regeneration by suppressing regional estrogen receptor type a expression.
Liver regeneration involves a significant variety of growth and paracrine factors. Octreotide has long been shown to inhibit liver regeneration, although the exact mechanism of its action remains unclear. This paper aims to examine the effect of long-term octreotide administration on the expression of the estrogen receptor type alpha (Era) as a potential novel pathway via which liver regeneration may be hindered. Sixty adult male Wistar rats were submitted to 70% (extensive) hepatectomy and subsequently randomized to receive either a subcutaneous injection of 50grams/kg body weight octreotide diluted in 1mL of 0.9% normal saline (SS group) or simply 1mL of 0.9% normal saline (NS group). Animals were followed up to 168 or 1440h (1 week and 1 month, respectively) post-hepatectomy and subsequently sacrificed. Removed livers were weighted, diluted in paraformaldehyde, embedded in paraffin wax, sliced at 5 micrometer intervals and prepared for the immunohistochemical detection of ERa. The control group labeling indices for both hepatocytes and cholangiocytes at 168 and 1440h were higher at a statistically significant degree compared to age-matched SS group animals. Interestingly, ERa expression is significantly increased over time in control animals for both cell types examined, while this is not true for animals receiving octreotide. In conclusion, octreotide-mediated inhibition of liver regeneration involves the long-term down-regulation of ERa expression in hepatocytes and cholangiocytes. This hormonal cross-talk may be of particular significance to explain sex-specific differences in liver repair dynamics.


Theoretical characterization of the (H2O)21 cluster: application of an n-body decomposition procedure.
Two low-energy minima of (H2O)21 with very different H-bonding arrangements have been investigated with the B3LYP density functional and RIMP2 methods, as well as with the TIP4P, Dang-Chang, AMOEBA, and TTM2-F force fields. The AMOEBA and TTM2-F model potentials give an energy ordering that agrees with the results of the electronic structure calculations, while the TIP4P and Dang-Chang models give the opposite ordering. Insight into the role of many-body polarization for establishing the relative stability of the two isomers is provided by an n-body decomposition of the energies calculated using the various theoretical methods.


Loss of heterozygosity on chromosome 1p in thyroid adenoma and medullary carcinoma, but not in papillary carcinoma.
We analyzed 53 loci on 21 chromosomes other than chromosome 4 to detect possible loss of heterozygosity in 31 thyroid tumors using polymorphic DNA markers that detect allelic deletions at specific chromosomal loci. Loss of heterozygosity on chromosomes 1, 7 and 12 was detected in one follicular thyroid adenoma, and on chromosome 1 in two medullary thyroid carcinomas. However, no loss of heterozygosity was detected at any of the loci examined in papillary thyroid carcinomas. These results suggest that chromosomal loss detected in thyroid adenoma is one of the signals for risk of premalignant transformation, and that inactivation of unknown genes on chromosome 1p contributes to tumorigenesis of medullary thyroid carcinoma. Some genetic changes other than chromosomal losses may participate in the tumorigenesis of papillary thyroid carcinoma.