A retrospective analysis of quetiapine in the treatment of pervasive developmental disorders.
The purpose of this study was to examine the effectiveness and tolerability of quetiapine for aggression, hyperactivity, and self-injury in pervasive developmental disorders (PDDs). The medical records of all patients with PDDs diagnosed according to DSM-IV criteria and treated with quetiapine were retrospectively reviewed. Patients who received quetiapine for at least 4 weeks and who were not concurrently treated with another antipsychotic or mood stabilizer were included. Improvement was measured with the Clinical Global Impressions-Improvement scale (CGI-I), with response determined by ratings of "much improved" or "very much improved." Data were collected from May 15, 2003 through November 30, 2003. Of 857 records reviewed, 20 patients (16 male, 4 female) (mean +/- SD age = 12.1 +/- 6.7 years; range, 5-28 years) received a quetiapine trial (mean +/- SD dosage = 248.7 +/- 198.4 mg/day; range, 25-600 mg/day) over a mean duration of 59.8 +/- 55.1 weeks (range, 4-180 weeks). Eight (40%) of 20 patients were judged "responders" to quetiapine; the mean CGI-I score for the entire group was 3.0 +/- 1.1 (minimally improved). A statistically significant improvement (p = .002) was found between a mean pretrial CGI-Severity of Illness scale (CGI-S) score of 5.1 +/- 0.6 (markedly ill) and a posttrial CGI-S score of 4.2 +/- 1.1 (moderately ill). Adverse effects occurred in 50% (N = 10) of patients and led to drug discontinuation in 15% (N = 3) of patients. Quetiapine was modestly effective for maladaptive behavior in patients with a PDD. Controlled studies are needed to further assess these preliminary findings.


Evaluating differences in density estimation for central Iowa butterflies using two methodologies.
The Pollard-Yates transect is a widely used method for sampling butterflies. Data from these traditional transects are analyzed to produce density estimates, which are then used to make inferences about population status or trends. A key assumption of the Pollard-Yates transect is that detection probability is 1.0, or constant but unknown, out to a fixed distance (generally 2.5 m on either side of a transect line). However, species-specific estimates of detection probability would allow for sampling at farther distances, resulting in more detections of individuals. Our objectives were to (1) evaluate butterfly density estimates derived from Pollard-Yates line transects and distance sampling, (2) estimate how detection probabilities for butterflies vary across sampling distances and butterfly wing lengths, and (3) offer advice on future butterfly sampling techniques to estimate population density. We conducted Pollard-Yates transects and distance-sampling transects in central Iowa in 2014. For comparison to densities derived from Pollard-Yates transects, we used Program DISTANCE to model detection probability (p) and estimate density (D) for eight butterfly species representing a range of morphological characteristics. We found that detection probability among species varied beyond 2.5 m, with variation apparent even within 5 m of the line. Such variation correlated with wing size, where species with larger wing size generally had higher detection probabilities. Distance sampling estimated higher densities at the 5-m truncation for five of the eight species tested. At this truncation, detection probability was <0.8 for all species, and ranged from 0.53 to 0.79. With the exception of the little yellow (Pyrisitia lisa), species with median wing length <5.0 mm had the lowest detection probabilities. We recommend that researchers integrate distance sampling into butterfly sampling and monitoring, particularly for studies utilizing survey transects >5 m wide and when smaller species are targeted.


Insights into oxazaphosphorine resistance and possible approaches to its circumvention.
The oxazaphosphorines cyclophosphamide, ifosfamide and trofosfamide remain a clinically useful class of anticancer drugs with substantial antitumour activity against a variety of solid tumors and hematological malignancies. A major limitation to their use is tumour resistance, which is due to multiple mechanisms that include increased DNA repair, increased cellular thiol levels, glutathione S-transferase and aldehyde dehydrogenase activities, and altered cell-death response to DNA damage. These mechanisms have been recently re-examined with the aid of sensitive analytical techniques, high-throughput proteomic and genomic approaches, and powerful pharmacogenetic tools. Oxazaphosphorine resistance, together with dose-limiting toxicity (mainly neutropenia and neurotoxicity), significantly hinders chemotherapy in patients, and hence, there is compelling need to find ways to overcome it. Four major approaches are currently being explored in preclinical models, some also in patients: combination with agents that modulate cellular response and disposition of oxazaphosphorines; antisense oligonucleotides directed against specific target genes; introduction of an activating gene (CYP3A4) into tumor tissue; and modification of dosing regimens. Of these approaches, antisense oligonucleotides and gene therapy are perhaps more speculative, requiring detailed safety and efficacy studies in preclinical models and in patients. A fifth approach is the design of novel oxazaphosphorines that have favourable pharmacokinetic and pharmacodynamic properties and are less vulnerable to resistance. Oxazaphosphorines not requiring hepatic CYP-mediated activation (for example, NSC 613060 and mafosfamide) or having additional targets (for example, glufosfamide that also targets glucose transport) have been synthesized and are being evaluated for safety and efficacy. Characterization of the molecular targets associated with oxazaphosphorine resistance may lead to a deeper understanding of the factors critical to the optimal use of these agents in chemotherapy and may allow the development of strategies to overcome resistance.


Frequency response characteristics of a birefringent lens with off-axis aberrations.
We report the frequency response characteristics of an optical system consisting of a lens made of a uniaxial birefringent crystal sandwiched between two linear polarizers; the lens has prespecified off-axis aberrations such as primary astigmatism and primary coma. An analytical expression is obtained for the optical transfer function of the proposed system by use of the autocorrelation of the pupil function over the lens aperture. Some specific cases are computed and illustrated graphically. It has been shown that the proposed system has imaging characteristics distinctly different from those of an ordinary glass lens, and these may be advantageous for better balancing of aberrations in conventional imaging systems.


[Enzymatic hydrolysates of food proteins for specialized foods for therapeutic and prophylactic nutrition].
The review considers some issues of obtaining, as well as physic-chemical, organoleptic, immunochemical (residual antigenicity) characteristics of enzymatic hydrolysates from food proteins (EHFP) that are widely used in food products for various purposes, as well as assessing their biological activity. The results of experimental works and patents, which describe the most widely used approaches to the production of EHFP with desired properties (hydrolysates for therapeutic and prophylactic products), as well as assessments of biological activity and immunochemical properties are given. The use of various enzyme preparations (of bacterial, fungal and animal origin), as well as one- and two-stage hydrolysis schemes and options for instrumentation of fermentolysis processes are considered. It is concluded that in order to achieve the required reduction in antigenicity for hydrolysates used as part of therapeutic (hypoallergenic) foods (to values not higher than 10-5 relative to the antigenicity of the original protein) membrane ultrafiltration stages are necessary. The main disadvantage of such hydrolysates is their unsatisfactory organoleptic properties (bitterness and high osmolarity) that can be improved using a number of additional technological approaches. The use of partial hydrolysates (or hydrolysates with an average degree of hydrolysis, with a residual antigenicity of 10-4 to 10-5) with significantly better organoleptic properties compared with deep hydrolysates in therapeutic foods is considered. Of considerable interest are the issues of immunomodulatory, antioxidant and hypoallergenic properties of EHFP. It has been suggested that soybean and chicken egg hydrolysates may be promising as functional ingredients with antimicrobial, antihypertensive and immunomodulatory effects in various specialized foods, as well as in cases of food intolerance only to cow milk proteins.


Comparative studies on limb morphogenesis in mice and bats: a functional genetic approach towards a molecular understanding of diversity in organ formation.
The basis of species-specific morphogenesis has been a topic of fascination and speculation for centuries. In 1828, Karl Ernst von Baer noted that at the pharyngula stage of development all vertebrate embryos are morphologically very similar. Most subsequent hypotheses have proposed that the vertebrate body plan develops by a conserved mechanism, and that divergent forms develop by differential elaboration on this basic plan. Gene cloning and expression studies have largely confirmed that the genetic pathways of embryonic patterning are highly conserved. The finding that the proteins encoded by paralogous and orthologous genes within and between species can functionally replace each another is no longer novel; in most cases this is the expected result. How, then, does divergent morphology arise between species? One hypothesis that fits well with comparative data is that divergent morphogenesis arises from genetic differences in the timing, level and pattern of orthologous gene expression during development. This idea is being tested using a functional genetic approach comparing limb morphogenesis between the mouse and bat.


Tension hemothorax following endovascular thoracic aortic transection repair: case report.
Thoracic aortic transection (TAT) is the second commonest cause of death from blunt trauma surpassed only by head injury and is associated with a mortality of 80% to 90%. The injury site is typically anteromedial at the aortic isthmus where differential shear forces act during rapid deceleration. The authors report a lateral aortic laceration managed by endovascular repair that required open thoracotomy for tension hemothorax resulting from an endoleak.


The forced expiratory time as a measure of small airway resistance.
1. In five subjects, ten consecutive forced expiratory spirograms were recorded on each of 6 different days and the total forced expiratory time (FET) on each spirogram was measured. The mean overall coefficient of variation of the FET was 11.3% and of the ratio forced vital capacity (FVC)/FET was 8%. 2. Twenty-two subjects with probable small (less than 2 mm diameter) airway dysfunction as manifested by a reduced (less than 75% predicted) maximum mid-expiratory flow (MMEF) in the middle 50% of the FVC with normal FVC and FEV1 (greater than 80% predicted) were studied before and after bronchodilatation. There was no significant correlation between change in FET and change in MMEF (r = 0.36, P greater than 0.01), but between change in MMEF (deltaMMEF) and change in FVC/FET (deltaFVC/FET) there was a positive correlation (r = 0.78, P less than 0.001). 3. In six of these twenty-two subjects, the deltaFVC/FET and deltaMMEF on bronchodilatation correlated well with the change in residual volume (deltaRV). but neither measurement correlated well with the change in the 'closing volume' measurement expressed as the ratio of phase 4/VC(%). The deltaFET did not correlate well with either deltaRV or delta[phase 4/VC(%)]. 4. In eighty-one selected normal subjects (FVC, FEV1 and MMEF all greater than 80% predicted) there was better correlation of age with the FVC/FET (r = -0.676) than with the FET (r = +0.43); both correlations were significant (P less than 0.001). 5. These results do not support the use of the FET as a suitable test of small airway function; however, the mean flow rate expressed as FVC/FET may, in the presence of a normal FEV1/FVC ratio, be an adequate test of small airway function.


Public health implications of environmental pollution in urban Indonesia.
The current levels of environmental pollutant in Indonesian cities, especially in Jakarta and Surabaya, as well as other cities in Java island, already have the potential for public health impact. Of particular concern and surveillance value are atmospheric particulate matter, sulphur dioxide, nitrous oxide, carbon monoxide, heavy metals (lead, cadmium and mercury) and pesticide residuals. These are also entering the food and water supply with particular risk to the socio-economically disadvantaged. Control strategies for environmental pollution are needed and public health programs for high risk groups are a must.


cis-1,3,4,6,7,11b-Hexahydro-2-methyl-7-phenyl-2H-pyrazino[2,1-a] isoquinoline: a new atypical antidepressant.
Molecular modelling studies suggested the synthesis of cis-1,3,4,6,7, 11b-hexahydro-2-methyl-7-phenyl-2H-pyrazino[2,1-a]isoquinoline (7a) as a rigid analogue of the atypical antidepressant mianserin. Acylation of 2,2-diphenylethylamine with chloroacetyl chloride gives the chloroacetamide (2). Cyclization of 2 with P2O5 in xylene provides 1-(chloromethyl)-3,4-dihydro-4-phenylisoquinoline (3). Amination of 3, followed by reduction, gives the isomeric (aminomethyl)tetrahydroisoquinolines (4a and 5). Treatment of 4a with diethyl oxalate, followed by reduction of the diamide with borane, provides 7a. A variety of N-substituted, aromatic substituted, and optically resolved derivatives were prepared and evaluated for anticholinergic, antihistaminic, and antidepressant activity. In particular, the target cis isomer 7a as predicted from the modelling studies appears to possess excellent atypical antidepressant activity. This activity resides in the (+)-S,S optical isomer 10, which has the same absolute configuration as (+)-mianserin.


Preoperative serum pyridinoline cross-linked carboxy-terminal telopeptide of type I collagen level predicts postoperative distant metastasis in patients with non-small-cell lung cancer.
To examine the relationship between preoperative serum pyridinoline cross-linked carboxy-terminal telopeptide of type I collagen (I-CTP) levels and postoperative distant metastasis in patients with non-small-cell lung cancer (NSCLC). We retrospectively reviewed 143 patients in whom preoperative serum I-CTP level was measured from January 2006 to March 2011, including 91 males and 52 females with an average age of 70.1 ± 8.2 years. Histological subtypes included adenocarcinoma (n = 95), squamous cell carcinoma (n = 34) and other (n = 14). Preoperative serum carcinoembryonic antigen (CEA) and cytokeratin-19 fragment (CYFRA) levels were also measured. Patients with abnormal renal function or preoperative bone fractures were excluded. The mean preoperative serum I-CTP level was 4.1 ± 1.6 ng/ml, and the preoperative serum I-CTP level was elevated (>4.5 ng/ml) in 29 patients. Distant metastasis was detected in 21 patients during the 39 ± 18 (range 1-79) months of follow-up. The rate of distant metastasis was significantly higher in patients with elevated preoperative serum I-CTP levels than those with normal preoperative I-CTP levels (≤4.5 ng/ml) (P < 0.0001). The 5-year recurrence-free survival rate was lower in patients with elevated preoperative serum I-CTP levels than those with normal preoperative I-CTP levels (41.8 vs 92.9%; P < 0.0001). An elevated preoperative serum I-CTP level predicts postoperative distant metastasis in patients with NSCLC.


The C-terminal extension of the beta7 subunit and activator complexes stabilize nascent 20 S proteasomes and promote their maturation.
The eukaryotic 20 S proteasome is formed by dimerization of two precursor complexes containing the maturation factor Ump1. Beta7/Pre4 is the only one of the 14 subunits forming the 20 S proteasome that is absent from these precursor complexes in Saccharomyces cerevisiae. Increased expression of Pre4 leads to a reduction in the level of precursor complex, indicating that Pre4 incorporation into these complexes is rate-limiting for their dimerization. When we purified these precursor complexes, we observed co-purification of Blm10, a large protein known to attach to the alpha ring surface of proteasomes. In contrast to single mutants lacking either Blm10 or the C-terminal extension of Pre4, a mutant lacking both grew extremely poorly, accumulated very high levels of precursor complexes, and was impaired in beta subunit maturation. The effect of blm10Delta on proteasome biogenesis is modest, apparently because the 19 S regulatory particle is capable of substituting for Blm10, as long as precursor complex dimers are stabilized by the Pre4 C terminus. We found that a mutation (sen3/rpn2) affecting the Rpn2 subunit inhibits attachment of the 19 S activator to the 20 S particle or its precursors. Although the sen3 mutation alone had no apparent effect on precursor complex dimerization and active site maturation, the sen3 blm10 double mutant was impaired in these processes. Together these data demonstrate that Blm10 and the 19 S activator have a partially redundant function in stabilizing nascent 20 S proteasomes and in promoting their activation.


OASIS voice mailbox inservices.
Assuring accuracy and reliability in OASIS data collection is more than just a one-time orientation. This article describes a lively ongoing OASIS educational program creatively using the agency's voice mail system. The article presents basic OASIS information and is a required reading for clinicians and managers who are interested in accurately collecting OASIS data.


Enhancing adenovirus-mediated gene transfer in vitro and in vivo by addition of protamine and hydrocortisone.
Inclusion of positively charged polymers such as protamine in adenovector formulations has been reported to improve the efficiency of adenovirus-mediated gene transfer in vitro and in vivo. On the other hand, corticosteroids are known to inhibit inflammation and thus might be useful in minimizing vector-related toxicity. In this study, we evaluated the combined effect of protamine sulfate and hydrocortisone on the efficiency of adenovirus-mediated gene transfer in vitro and in vivo. Protamine and hydrocortisone at different concentrations were added to adenovector formulations. In vitro transgene expression with or without inclusion of protamine and hydrocortisone was evaluated in the breast cancer cell lines MDA-MB-231 and MCF7 and the lung cancer cell lines A549 and H460. In vivo transgene expression in the mouse lung was determined after aerosolized vector delivery. The combination of 2 micro g/ml protamine and 125 ng/ml hydrocortisone significantly increased transgene expression in vitro in all the cell lines tested. Protamine is only effective when it is added to cells before or together with adenovectors, whereas hydrocortisone is effective when it is added to cells before, together with, or after adenovectors. Inclusion of protamine and hydrocortisone also augmented apoptosis induction caused by adenovectors expressing proapoptotic genes in cancer cells. Moreover, protamine and hydrocortisone dramatically enhanced transgene expression in the mouse lung after aerosolized vector delivery. Inclusion of protamine and hydrocortisone in adenovector formulations can improve adenovector-mediated gene expression and may be useful for clinical applications of current adenovirus-mediated gene therapy.


The peripheral metabolism of triiodothyronine in normal subjects and in patients with hyperthyroidism.
In order to assess the contribution of 3.3',5-triiodo-L-thyronine (T(3)) to overall thyroid hormone economy, conjoint measurements of the kinetics of peripheral T(3) metabolism and the total concentration of T(3) in serum were made in a group of normal subjects and in a group of patients with hyperthyroid Graves' disease. As judged from the disappearance of trichloroacetic acid-precipitable (131)I from serum after a single intravenous dose of labeled T(3), the following mean values were obtained in the normal subjects: volume of distribution, 43 liters or 0.62 liter/kg; fractional turnover rate. 52% per 24 hr: clearance rate, 22.3 liters/24 hr: and absolute disposal rate, 60 mug/24 hr. In the patients with untreated hyperthyroidism, values for all these functions were greatly increased. After treatment, the volume of T(3) distribution returned to normal but the fractional turnover rate remained abnormally rapid.


Role of the disulfide bond in stabilizing and folding of the fimbrial protein DraE from uropathogenic Escherichia coli.
Dr fimbriae are homopolymeric adhesive organelles of uropathogenic Escherichia coli composed of DraE subunits, responsible for the attachment to host cells. These structures are characterized by enormously high stability resulting from the structural properties of an Ig-like fold of DraE. One feature of DraE and other fimbrial subunits that makes them peculiar among Ig-like domain-containing proteins is a conserved disulfide bond that joins their A and B strands. Here, we investigated how this disulfide bond affects the stability and folding/unfolding pathway of DraE. We found that the disulfide bond stabilizes self-complemented DraE (DraE-sc) by ∼50 kJ mol-1 in an exclusively thermodynamic manner, i.e. by lowering the free energy of the native state and with almost no effect on the free energy of the transition state. This finding was confirmed by experimentally determined folding and unfolding rate constants of DraE-sc and a disulfide bond-lacking DraE-sc variant. Although the folding of both proteins exhibited similar kinetics, the unfolding rate constant changed upon deletion of the disulfide bond by 10 orders of magnitude, from ∼10-17 s-1 to 10-7 s-1 Molecular simulations revealed that unfolding of the disulfide bond-lacking variant is initiated by strands A or G and that disulfide bond-mediated joining of strand A to the core strand B cooperatively stabilizes the whole protein. We also show that the disulfide bond in DraE is recognized by the DraB chaperone, indicating a mechanism that precludes the incorporation of less stable, non-oxidized DraE forms into the fimbriae.


PTSD and loss: preliminary findings from a territory-wide epidemiology study in Hong Kong.
The study examined the prevalence of trauma and posttraumatic stress disorder (PTSD) symptoms among community dwelling Chinese adults in Hong Kong. The relationship of traumatic life events (including loss) and mental health has been investigated. The sampling of the collaborative study (HKMMS: Hong Kong Mental Morbidity Survey) adopts a multi-stage stratification approach with the distribution of residential premises in different geographical districts and the relative proportion of private versus public housing units taken into consideration. In Phase I of this study, 4,644 adults were screened for PTSD with the Trauma Screening Questionnaire (TSQ) and Life Event Checklist (LEC), Beck's scales and CIS-R (Revised Clinical Interview Schedule). In Phase II of the study, clinical psychologists conducted the Structured Clinical Interview for DSM Disorders (SCID) for 92 participants (results not reported here). Among Phase I participants, 65% reported traumatic experience (including 18% who reported personal experience of sudden death of significant others). Age and gender make a difference in traumatic experience. When compared to participants who reported no traumatic experience in the past, participants who reported to have personal experience of sudden death of significant others or other traumatic experiences were found to have higher TSQ scores, higher psychological distress, lower social support (PSS: Multidimensional Scale of Perceived Social Support), and lower life functioning (SOFAS: Social and Occupational Functioning Assessment Scale), p<0.001. Findings of hierarchical regression showed that type of trauma (i.e., loss, other trauma, or no trauma) contributed significantly to the prediction of all the mental health indices after demographic and social variables were controlled. Public education on the association of traumatic experience and psychological health, as well as the monitoring of mental health for at-risk individuals are suggested for early identification of people in need of mental health services.


Pheromonal control of aggressive display in siamese fighting fish (Betta splendens).
Male Siamese fighting fish displayed and respirated from the surface more frequently in water containing secretions collected from non-displaying male conspecifics than they did in clean water. Secretions collected from males given the opportunity to display to a mirror for 16, 30, or 45 min. did not affect display activity. However, secretions collected from males allowed to display to a mirror for 16 min. produced an increase in respiration rates. Secretions collected from males which had been stressed by electric shock resulted in decrements in aggressive display. Taken together, results of these experiments suggest that male Siamese fighting fish secrete substances which affect mirror-induced aggression and respiration rates.


Seasonal patterns of luteal cyclicity in young red deer (Cervus elaphus) and sambar deer (Cervus unicolor).
Seasonal onset of pubertal ovulation and incidence of luteal cyclicity was assessed from plasma progesterone profiles over 15 months for tame red deer (n = 7) and sambar deer (n = 7) hinds. Seasonal responses to photoperiod were determined from plasma prolactin profiles. All red deer attained puberty at 17-18 months of age in May-June and expressed 3-6 luteal cycles of length 20.0+/-10.4 days (mean+/-s.e.m.) over 52-102 days. Six sambar deer attained puberty at 7-19 months of age, between August and December. Duration of luteal cyclicity was variable. While one animal remained continuously cyclic for 13 months, most entered anoestrus between November and February. The mean length of the luteal cycle was 17.2+/-0.3 days. While red deer exhibited strongly seasonal patterns of prolactin secretion, sambar deer showed no such seasonal trends. The data collectively indicate that young sambar hinds at temperate latitudes exhibit loosely defined patterns of reproductive seasonality that are 4-6 months out of phase with those of red deer, although some individuals may be non-seasonal. Failure to express seasonal patterns of prolactin secretion indicates that sambar deer may not perceive photoperiodic cues to the same extent as do red deer.


Genetic data and the listing of species under the U.S. Endangered Species Act.
Genetic information is becoming an influential factor in determining whether species, subspecies, and distinct population segments qualify for protection under the U.S. Endangered Species Act. Nevertheless, there are currently no standards or guidelines that define how genetic information should be used by the federal agencies that administer the act. I examined listing decisions made over a 10-year period (February 1996-February 2006) that relied on genetic information. There was wide variation in the genetic data used to inform listing decisions in terms of which genomes (mitochondrial vs. nuclear) were sampled and the number of markers (or genetic techniques) and loci evaluated. In general, whether the federal agencies identified genetic distinctions between putative taxonomic units or populations depended on the type and amount of genetic data. Studies that relied on multiple genetic markers were more likely to detect distinctions, and those organisms were more likely to receive protection than studies that relied on a single genetic marker. Although the results may, in part, reflect the corresponding availability of genetic techniques over the given time frame, the variable use of genetic information for listing decisions has the potential to misguide conservation actions. Future management policy would benefit from guidelines for the critical evaluation of genetic information to list or delist organisms under the Endangered Species Act.


Massive hemothorax after removal of subclavian vein catheter: a very unusual complication.
A case of massive hemothorax developing a few minutes after removal of a central venous catheter is described in a 51-yr-old woman, who had undergone a renal transplant. The patient had an arteriovenous fistula for hemodialysis on the same side as the central catheter. The mechanism of the onset of this complication is discussed. We recommend avoiding positioning a central catheter on the same side as an arm arteriovenous fistula. Furthermore, we think it is necessary to monitor patients after removal, as is usually done after positioning, to detect this potentially fatal complication.


Evidence of loss of heterozygosity of the PTCH gene in orthokeratinized odontogenic cyst.
The orthokeratinized odontogenic cyst (OOC) is an odontogenic cyst of unknown etiology. Clinical, histological, and biological differences are reported between keratocystic odontogenic tumor (KOT) and OOC. PTCH is a tumor suppressor gene related to sonic hedgehog (SHH) pathway important in embryological development. Considering that alterations in this pathway have been described in sporadic and nevoid basal cell syndrome-associated KOT, we tested the hypothesis that OOC is also associated with loss of heterozygosity (LOH) of the PTCH gene. Seven samples of OOC and seven of KOT were included in the study. D9S287, D9S196, and D9S127 microsatellite markers located in the region of PTCH gene, at chromosome 9q, were investigated for LOH. There was loss in at least one locus in 5/7 KOT and in 4/7 OOC samples. The present finding demonstrates that, despite the existence of clinical, morphological, immunohistochemical, and biological behavior differences between OOC and KOT, both harbor similar genetic alterations at 9q.


Ultrasonographic evaluation of salivary gland diseases.
Ultrasonography is an imaging modality in which the high frequency sound waves are sent into the tissues and the acoustic impedence of the tissues are received, amplified and imaged. The echoes of the tissues vary according to their densities. Ultrasonography is applied in the field of medicine, in the evaluation of soft tissues, to record their movements and to assess their vascularity. In the oro-facial region, ultrasonography is employed in the evaluation of salivary glands, cervical lymph nodes, in soft tissues and post-operative swellings. Ten interesting cases of salivary gland diseases are presented here, each case showing a characteristic sonographic feature and providing a useful diagnostic clue in the identification of the disease.


Charge Transfer in Iridate-Manganite Superlattices.
Charge transfer in superlattices consisting of SrIrO3 and SrMnO3 is investigated using density functional theory. Despite the nearly identical work function and nonpolar interfaces between SrIrO3 and SrMnO3, rather large charge transfer was experimentally reported at the interface between them. Here, we report a microscopic model that captures the mechanism behind this phenomenon, providing a qualitative understanding of the experimental observation. This leads to unique strain dependence of such charge transfer in iridate-manganite superlattices. The predicted behavior is consistently verified by experiment with soft X-ray and optical spectroscopy. Our work thus demonstrates a new route to control electronic states in nonpolar oxide heterostructures.


Distinguishing between a power law and a Pareto distribution.
This paper introduces the location Pareto distribution as a natural extension of the power law distribution and gives a likelihood ratio test for choosing between the two models. Some properties of the distribution and test are thoroughly investigated, and applications to real data are provided. For large values of the observations the two models perform similarly; this explains why some classical approaches are very insensitive to the differentiation between them. The likelihood ratio test between the two models is simple to use and has a high level of discrimination power. It is recommended when the complementary cumulative distribution function exhibits linearity on a log-log scale.


ACOG Committee Opinion No. 422: at-risk drinking and illicit drug use: ethical issues in obstetric and gynecologic practice.
Drug and alcohol abuse is a major health problem for American women regardless of their socioeconomic status, race, ethnicity, and age. It is costly to individuals and to society. Obstetrician-gynecologists have an ethical obligation to learn and use a protocol for universal screening questions, brief intervention, and referral to treatment in order to provide patients and their families with medical care that is state-of-the-art, comprehensive, and effective. In this Committee Opinion, the American College of Obstetricians and Gynecologists' Committee on Ethics proposes an ethical rationale for this protocol in both obstetric and gynecologic practice, offers a practical aid for incorporating such care, and provides guidelines for resolving common ethical dilemmas related to drug and alcohol use that arise in the clinical setting.


Anomalous diffusion of fatty acid vesicles driven by adhesion gradients.
The motion of fatty acid vesicles driven by adhesion gradients of a liquid substrate (Langmuir monolayer) has been investigated. Trajectories of the vesicle motion reveal not only heterogeneity among vesicles in different regions of the monolayer but also heterogeneity within single-vesicle trajectories. Trajectories often exhibit complex behaviors such as circular and oscillating ones. Some vesicles exhibit intermittent dynamics that results in jump diffusion trajectories. In many vesicles their mean square displacements and effective diffusion coefficients exhibit a wide range of behaviors: (i) simple Brownian, (ii) subdiffusive, (iii) superdiffusive, and (iv) their combined motions. Even in the resting regime that the vesicle does not move substantially it exhibits active fluctuations due to spatio-temporal variations of the adhesion gradients of the monolayer. The results are compared with those in motor protein-driven transport of micrometer-sized particles bound to the cytoskeletal network and polymerization motor transport in the cell previously reported.


Role of manual therapy with exercise regime versus exercise regime alone in the management of non-specific chronic neck pain.
To evaluate the role of manual therapy with exercise regime versus exercise regime alone in the management of non-specific chronic neck pain. In this 62 subjects randomized controlled trial 31 subjects in group A received manual therapy (manipulation) with supervised exercise regime whilst 31 subjects in group B performed only supervised exercise regime for the period of 3 weeks. Both groups had a home exercise program consisted of strengthening exercises for neck/scapuluar stability, stretching and general range of motion exercises for neck with advice regarding posture awareness and correction for 3 months. The results suggested significant reduction in pain intensity level in both groups; over 3 weeks and 12 weeks' time period in relation to baseline on visual analog scale (p=0.001). Similarly, statistically significant improvements noticed in Neck Disability Index (NDI) (p=0.0001) in both groups while looking at baseline data with reference to 12 weeks' time period. On closer inspection, the manual therapy (manipulation) with exercise regime appeared as a favorable treatment preference compared with exercise regime alone.


The combination of oxalic acid with power ultrasound fully degrades chrysotile asbestos fibres.
The simultaneous action of power ultrasound and oxalic acid, as a chelating agent, rapidly converts chrysotile asbestos into water soluble material and a non-asbestos debris, not classifiable as hazardous under worldwide safety regulations.


Cardiac Autonomic Neuropathy in Prediabetes: A Case-Control Study.
Early detection and diagnosis of diabetic autonomic neuropathy, especially cardiac autonomic neuropathy (CAN), have gained attention recently because of their elevated cardiovascular mortality risk. Although the connection between type 2 diabetes mellitus and autonomic neuropathy is well established, evidence is emerging that the association might predate the stage of prediabetes. The present study was undertaken to compare the prevalence of CAN in prediabetes versus that in normoglycemic controls. The study population was selected by purposive sampling from individuals attending a tertiary care hospital from January 2018 to June 2019. Fifty individuals with prediabetes diagnosed by the American Diabetes Association's glycated haemoglobin criteria and 50 age- and gender-matched healthy controls were recruited. CAN was assessed by standard cardiovascular reflex tests, as described by Ewing and Clarke. Changes in R-R with deep breathing, Valsalva manoeuver, and changes in blood pressure (BP) in response to standing and sustained handgrip were evaluated. Three-time domains [standard deviation of normal-to-normal intervals (SDNN), root mean square of successive RR intervals (rMSSD) and percentage of successive normal to normal R-R (NN) intervals that differ by more than 50 ms (pNN50)] and four frequency domain indices [very low-frequency band (VLF), low-frequency band (LF), high-frequency band (HF), LF/HF ratio) of heart rate variability (HRV)] were examined. The mean heart rate was 71.37 ± 7.94 and 65.59 ± 8.73 beats/min in patients with prediabetes and controls, respectively (P < 0.05). All three-time-domain indices of HRV were significantly lower in persons with prediabetes compared to controls. The peak frequency of LF, peak power of LF, normalised unit of LF, and LF/HF ratio was significantly lower in subjects with prediabetes than in controls. There was no difference in the traditional cardiovascular autonomic reflex testing. Our study demonstrates the presence of subclinical autonomic dysfunction in persons with prediabetes. Early detection of CAN in prediabetes can have future implications for cardiovascular risk reduction.


Oral bacterial DNA findings in pericardial fluid.
We recently reported that large amounts of oral bacterial DNA can be found in thrombus aspirates of myocardial infarction patients. Some case reports describe bacterial findings in pericardial fluid, mostly done with conventional culturing and a few with PCR; in purulent pericarditis, nevertheless, bacterial PCR has not been used as a diagnostic method before. To find out whether bacterial DNA can be measured in the pericardial fluid and if it correlates with pathologic-anatomic findings linked to cardiovascular diseases. Twenty-two pericardial aspirates were collected aseptically prior to forensic autopsy at Tampere University Hospital during 2009-2010. Of the autopsies, 10 (45.5%) were free of coronary artery disease (CAD), 7 (31.8%) had mild and 5 (22.7%) had severe CAD. Bacterial DNA amounts were determined using real-time quantitative PCR with specific primers and probes for all bacterial strains associated with endodontic disease (Streptococcus mitis group, Streptococcus anginosus group, Staphylococcus aureus/Staphylococcus epidermidis, Prevotella intermedia, Parvimonas micra) and periodontal disease (Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, Treponema denticola, Fusobacterium nucleatus, and Dialister pneumosintes). Of 22 cases, 14 (63.6%) were positive for endodontic and 8 (36.4%) for periodontal-disease-associated bacteria. Only one case was positive for bacterial culturing. There was a statistically significant association between the relative amount of bacterial DNA in the pericardial fluid and the severity of CAD (p=0.035). Oral bacterial DNA was detectable in pericardial fluid and an association between the severity of CAD and the total amount of bacterial DNA in pericardial fluid was found, suggesting that this kind of measurement might be useful for clinical purposes.


Cyclooxygenase-2 biology.
In mammalian cells, eicosanoid biosynthesis is usually initiated by the activation of phospholipase A(2) and the release of arachidonic acid from membrane phospholipids in response to the interaction of a stimulus with a receptor on the cell surface. Arachidonic acid is subsequently transformed by the enzyme cyclooxygenase (COX) to prostaglandins (PGs) and thromboxane (TX). The COX pathway is of particular clinical relevance because it is the major target for non-steroidal anti-inflammatory drugs, which are commonly used for relieving inflammation, pain and fever. In 1991, it was disclosed that COX exists in two distinct isozymes (COX-1 and COX-2), one of which, COX-2, is primarily responsible for inflammation but apparently not for gastrointestinal integrity or platelet aggregation. For this reason, in recent years, novel compounds that are selective for this isozyme, the so-called selective COX-2 inhibitors or COXIBs, which retain anti-inflammatory activity but minimize the risk of gastrointestinal toxicity and bleeding, have been developed. This review article provides an overview and an update on the progress achieved in the area of COX-2 and PG biosynthesis and describes the role of COX-2 in health and disease. It also discusses some unresolved issues related to the use of selective COX-2 inhibitors as a safe and promising therapeutic option not only for the treatment of inflammatory states but also for cancer.


Area-based variations in obesity are more than a function of the food and physical activity environment : area-based variations in obesity.
This study examines the area-based variations in obesity from a community-based epidemiologic survey of Boston, MA, USA, using a geographic information system and multilevel modeling techniques. A combination of quantitative and qualitative methods was used to assess whether a function of the food and the physical activity (PA) environment can explain the body weight of residents. First, a series of multilevel analyses was conducted after accounting for the well-established individual determinants and capturing a wide range of environmental attributes to represent a more realistic portrayal of urban typology. Second, the results of multilevel analysis were framed into the theoretical model of area-based variations in obesity to qualitatively summarize the association of contextual factors with the body weight of residents. Based on the overall correlation, the area-based variations defined by a function of the food and PA environment seem to be insufficient in explaining the body weight of residents. By testing the cross-level interactions of gender and race/ethnicity with contextual factors, the results suggest that the concept of area-based variations in obesity will have to consider how residents behave differently within a given environment. More research is needed to better understand the contextual determinants of obesity so as to put forth population-wide interventions.


Fluorescence polarisation activity-based protein profiling for the identification of deoxynojirimycin-type inhibitors selective for lysosomal retaining alpha- and beta-glucosidases.
Lysosomal exoglycosidases are responsible for processing endocytosed glycans from the non-reducing end to produce the corresponding monosaccharides. Genetic mutations in a particular lysosomal glycosidase may result in accumulation of its particular substrate, which may cause diverse lysosomal storage disorders. The identification of effective therapeutic modalities to treat these diseases is a major yet poorly realised objective in biomedicine. One common strategy comprises the identification of effective and selective competitive inhibitors that may serve to stabilize the proper folding of the mutated enzyme, either during maturation and trafficking to, or residence in, endo-lysosomal compartments. The discovery of such inhibitors is greatly aided by effective screening assays, the development of which is the focus of the here-presented work. We developed and applied fluorescent activity-based probes reporting on either human GH30 lysosomal glucosylceramidase (GBA1, a retaining β-glucosidase) or GH31 lysosomal retaining α-glucosidase (GAA). FluoPol-ABPP screening of our in-house 358-member iminosugar library yielded compound classes selective for either of these enzymes. In particular, we identified a class of N-alkyldeoxynojirimycins that inhibit GAA, but not GBA1, and that may form the starting point for the development of pharmacological chaperone therapeutics for the lysosomal glycogen storage disease that results from genetic deficiency in GAA: Pompe disease.


Substance P theory: a unique focus on the painful and painless phenomena of cluster headache.
These studies of cluster headache (CH) focus on two key features of pain transmission: a) sensory nerves when stimulated, as well as the expected afferent transmission, also display an efferent function which affects capillaries, glands, and smooth muscle (of the iris in CH); substance P (SP) and allied transmitters such as Vasoactive Intestinal Peptide (VIP) and Calcitonin Gene-Related Peptide (CGRP) are the main agonists of this dual afferent-efferent function; b) impaired pain transmission (deafferentation-like condition) provokes a rostral spread of neuronal irritability and automatic firing ("quasi epileptic foci") producing a clinical predilection for pain with the generation of "spontaneous" pains along the sensory pathways. The substrates studied in the present experiments are the iris, salivary glands, and nasal mucosa. 1) Iris: the conjunctival instillation of SP induces isocoric miosis both in CH sufferers and in normals, thus excluding gross SP receptoral dysfunction of the iris muscle in CH. Electrical stimulation of extraocular (infratrochlear) endings of the first branch of the trigeminal nerve provokes a miosis, which is significantly less in the symptomatic eye than in the contralateral one. This miosis is ascribed to a retrograde release of SP, induced by electrical stimulation of the trigeminal ophthalmic branch. The relatively poor miosis in the painful eye could correlate with a deficient release of SP from the sensory terminals in the iris. 2) Salivary glands: an increase of substance P-like immunoreactivity is found in the saliva taken from the asymptomatic side, but not from the painful side during a cluster headache attack, thus showing at this level also an asymmetry as previously shown in other head structures. 3) Nasal mucosa: intranasal application of capsaicin, a powerful releaser of SP from sensory terminals, evokes an immediate burning pain in the ipsilateral nasal, ocular, and temporal areas, as well as lacrimation and rhinorrhea. A gradual decrease (tachyphylaxis) of these phenomena is consistently observed after few days of daily nasal administration of capsaicin. When this treatment is applied to CH patients, a rapid decrease in the number and intensity of attacks, and even disappearance of symptoms accompanies the decline of the capsaicin-induced manifestations. Local (nasal) capsaicin, in spite of evoking immediately the same vegetative (rhinorrhea, lacrimation, conjunctival congestion) and in part nociceptive (transient nasal, ocular, temporal burning) phenomena of CH, never has been able to provoke delayed spontaneous-CH like attacks. Such delayed provoked attacks, one of the most pregnant phenomena in CH investigations, are almost constantly evoked by systemic stimuli.(ABSTRACT TRUNCATED AT 400 WORDS)


An Overview of Helicobacter pylori VacA Toxin Biology.
The VacA toxin secreted by Helicobacter pylori enhances the ability of the bacteria to colonize the stomach and contributes to the pathogenesis of gastric adenocarcinoma and peptic ulcer disease. The amino acid sequence and structure of VacA are unrelated to corresponding features of other known bacterial toxins. VacA is classified as a pore-forming toxin, and many of its effects on host cells are attributed to formation of channels in intracellular sites. The most extensively studied VacA activity is its capacity to stimulate vacuole formation, but the toxin has many additional effects on host cells. Multiple cell types are susceptible to VacA, including gastric epithelial cells, parietal cells, T cells, and other types of immune cells. This review focuses on the wide range of VacA actions that are detectable in vitro, as well as actions of VacA in vivo that are relevant for H. pylori colonization of the stomach and development of gastric disease.


Setup error assessment based on "Sphere-Mask" Optical Positioning System: Results from a multicenter study.
The setup accuracy plays an extremely important role in the local control of tumors. The purpose of this study is to verify the feasibility of "Sphere-Mask" Optical Positioning System (S-M_OPS) for fast and accurate setup. From 2016 to 2021, we used S-M_OPS to supervise 15441 fractions in 1981patients (with the cancer in intracalvarium, nasopharynx, esophagus, lung, liver, abdomen or cervix) undergoing intensity-modulated radiation therapy (IMRT), and recorded the data such as registration time and mask deformation. Then, we used S-M_OPS, laser line and cone beam computed tomography (CBCT) for co-setup in 277 fractions, and recorded laser line-guided setup errors and S-M_OPS-guided setup errors with CBCT-guided setup result as the standard. S-M_OPS supervision results: The average time for laser line-guided setup was 31.75s. 12.8% of the reference points had an average deviation of more than 2 mm and 5.2% of the reference points had an average deviation of more than 3 mm. Co-setup results: The average time for S-M_OPS-guided setup was 7.47s, and average time for CBCT-guided setup was 228.84s (including time for CBCT scan and manual verification). In the LAT (left/right), VRT (superior/inferior) and LNG (anterior/posterior) directions, laser line-guided setup errors (mean±SD) were -0.21±3.13mm, 1.02±2.76mm and 2.22±4.26mm respectively; the 95% confidence intervals (95% CIs) of laser line-guided setup errors were -6.35 to 5.93mm, -4.39 to 6.43mm and -6.14 to 10.58mm respectively; S-M_OPS-guided setup errors were 0.12±1.91mm, 1.02±1.81mm and -0.10±2.25mm respectively; the 95% CIs of S-M_OPS-guided setup errors were -3.86 to 3.62mm, -2.53 to 4.57mm and -4.51 to 4.31mm respectively. S-M_OPS can greatly improve setup accuracy and stability compared with laser line-guided setup. Furthermore, S-M_OPS can provide comparable setup accuracy to CBCT in less setup time.


Is it possible to achieve functional recovery in schizophrenia? A qualitative and quantitative analysis of psychiatrist´s opinion.
Psychiatrist´s opinion on functional recovery (FR) of patients with schizophrenia may modulate the therapeutic expectations and how to manage the disease. This study aims to know the opinion of psychiatrists on FR, and to analyze the relationship between functioning and symptoms. A qualitative and quantitative, descriptive and exploratory study. Two data collection techniques were used: a) a written survey consisting of 12 questions, directly, anonymously and confidentially answered by 132 psychiatrists; b) 5 focus group discussions involving 42 psychiatrists. 69.8% of psychiatrists considered realistic to get FR in schizophrenia and another 30.1% chose an intermediate response. The clinical priority for the 94% is to optimize the functional outcome of their patients, but only 14.4% commonly use rating scales. 91.7 % believed that there are differences between typical and atypical antipsychotics in terms of FR, and 83.3% believed essential to implement psychosocial interventions to achieve this goal. According to psychiatrists, FR is a complex concept and a primary therapeutic goal. Negative and cognitive symptoms are the strongest predictors of poor functioning. The low functioning of a patient, even in symptomatic stability, usually requires a re-evaluation of treatment. For psychiatrists, FR is a useful concept and a clinical priority, although there are doubts about how to achieve it.


Seven possible mechanisms for Escherichia coli diarrhea.
Escherichia coli has long been recognized as a potential enteric pathogen. This versatile organism has taught us much about the virulence traits responsible for a wide range of types of diarrheal diseases and their pathogenesis. Seven possible mechanisms for E. coli diarrhea are presented in this article.


Surgical treatment of duodenal ulcer.
This paper reviews the pathophysiology of peptic ulcer disease, the role of the vagus and gastrin in the control of gastric acid secretion and motility and the rationale for modern operations for peptic ulcer. The importance of arriving at a balanced decision before recommending surgery for a peptic ulcer is discussed. The indications for surgery in elective and emergency cases are defined and the results reviewed critically and compared with medical treatment. Novel operative procedures are mentioned but still await validation follow-up studies before their final assessment. Well tried operations should not be dismissed lightly and the importance of prospective randomized trials to evaluate new procedures is emphasized.


Improving the heterointerface in hybrid organic-inorganic perovskite solar cells by surface engineering: Insights from periodic hybrid density functional theory calculations.
A periodic hybrid density functional theory computational strategy is presented to model the heterointerface between the methylammonium lead iodide (MAPI) perovskite and titanium dioxide (TiO2 ), as found in perovskite solar cells (PSC), where the 4-chlorobenzoic acid (CBA) ligand is used to improve the stability and the band alignment at the interface. The CBA ligand acts as a bifunctional linker to efficiently connect the perovskite and the oxide moieties, ensuring the stability of the interface through Ti-O and Pb-Cl interactions. The computed density of states reveals that the perovskite contributes to the top of the valence band while the oxide contributes to the bottom of the conduction band with a direct bandgap of 2.16 eV, indicating a possible electron transfer from MAPI to TiO2 . Dipole moment analysis additionally reveals that the CBA ligand can induce a favorable effect to improve band alignment and thus electron transfer from MAPI to TiO2 . This latter has been quantified by calculation of the spin density of the reduced MAPI/CBA/TiO2 system and indicates an almost quantitative (99.94%) electron transfer from MAPI to TiO2 for the surface engineered system, together with an ultrafast electron injection time in the femtosecond timescale. Overall, the proposed DFT-based computational protocol therefore indicates that surface engineering and the use of a bifunctional linker can lead to a better stability, together with improved band alignment and electron injection in PSC systems.


Changes in PAF (platelet-activating factor) production during cell cycle of yeast Saccharomyces cerevisiae.
Yeast Saccharomyces cerevisiae cells were cultured synchronously and the change of platelet-activating factor (PAF) production during the cell cycle was investigated at each phase of the cycle. The basal PAF contents of diploid AKU4103 cells in G1 and M phases were higher than those of cells in S phase. Both diploid and haploid strains showed the same level of PAF production in response to the calcium ionophore A23187. A23187-stimulated PAF productions of cells in G1 and M phases were about 20 times higher than that of cells in S phase. The contents of PAF precursor in G1 and M phases cells of AKU4103 were higher than those in S phase cells, and the ratio of A23187-stimulated PAF to the precursor was highest in G1 phase cells. We also examined the change in a PAF-synthesizing enzyme, acetyltransferase, activity during the cell cycle using a microsomal fraction. Specific activity was the highest at G1 phase, and total activity was higher at M phase. The enzyme activities of cells in S phase of strains AKU4103 and RAY-3Aa were one-third and one-tenth of those in G1 phase of corresponding cells, respectively. These results suggest that PAF production was higher at G1 and M phases and lower at S phase, and changes in PAF productivity during cell cycle were related to the precursor contents and the synthesizing enzyme activities in those cells. These data suggest that PAF may control the cell cycle phase in budding yeast.


HBIG prophylaxis for perinatal HBV infections--final report of the Taiwan trial.
A randomized double blind placebo controlled efficacy trial of hepatitis B immunoglobulin (HBIG) for prevention of the mother to infant transmitted HBsAg carrier state was conducted in Taiwan where the carrier rate in the general population is 15% to 20%. HBIG was given immediately after birth to infants of e antigen positive HBsAg carrier mothers and all infants were followed for at least 15 months. Among 61 placebo recipients the carrier rate was 92%; compared with 26% among 57 infants who received 0.5 ml HBIG at birth, three months and six months and 54% among 67 infants who received a single 1.0 ml dose of HBIG at birth only. Efficacy was 71% and 42% respectively for the two treatment schedules. The most common response of HBIG-treated infants was passive-active immunization which was 27% in single dose group and 61% in three doses group. Some of the infants who became carriers were probably infected as HBIG protection waned and we expect that higher efficacy can be achieved by HB vaccine in conjunction with HBIG.


The clever fetus: responding to inflammation to minimize lung injury.
Clinical and experimental information indicate that fetal exposure to inflammation can induce lung maturation. This inflammation may be chronic and indolent. We present clinical and experimental information that challenge assumptions about chorioamnionitis associated infection/inflammatory exposures to the fetus. We question the assumption that the fetal compartment is sterile, and that delivery is inevitable if chronic infection/inflammation is present. We demonstrate that the preterm fetus can develop a brisk and adequate inflammatory response, and the fetus also can quickly modulate and downregulate inflammation to prevent injury. The fetus at risk of early preterm delivery may be exposed to both chorioamnionitis and glucocorticoids. Both exposures can either increase or decrease fetal inflammatory responses depending on the timing of the exposures. The immunomodulatory ability of the fetus to fetal exposures remains an unexplored research field.


Modified approach for keratinized tissue augmentation in multiple teeth.
This case report demonstrated a modified technique of free gingival graft (FGG) aiming to increase keratinized attached tissue in large recipient areas. A FGG to increase the amount of attached gingival tissue, facilitate oral hygiene, and prevent further clinical attachment loss was realized in two patients. Because the extensive recipient area, a modified technique was performed to obtain a smaller graft of the donor area. A template of the graft was made about 25%-30% smaller than the total recipient area. After graft removal, interspersed incisions were made in the upper and lower edges of it. After 9-24 months of follow-up, the final width of the keratinized tissue was 4.0-4.4 times larger in comparison to initial clinical condition. In conclusion, this FGG technique can be considered an alternative to gain sufficient amount of keratinized gingival tissue using a smaller graft.


Emergencies of the biliary tract.
The traditional approach to urgent therapy of biliary tract disease has undergone significant change. Technologic advances now permit a nonoperative approach to acute cholangitis, acute gallstone pancreatitis and hemobilia. Acute cholecystitis continues to be treated surgically in most cases. The clinical use of such nonoperative therapy has been guided mainly by retrospective data. The precise indications and optimal timing for endoscopic and radiologic therapy and their relationship to traditional surgical therapy remains to be defined by careful prospective evaluation.


Nitric oxide isotopic analyzer based on a compact dual-modulation Faraday rotation spectrometer.
We have developed a transportable spectroscopic nitrogen isotopic analyzer. The spectrometer is based on dual-modulation Faraday rotation spectroscopy of nitric oxide isotopologues with near shot-noise limited performance and baseline-free operation. Noise analysis indicates minor isotope ((15)NO) detection sensitivity of 0.36 ppbv·Hz(-1/2), corresponding to noise-equivalent Faraday rotation angle (NEA) of 1.31 × 10(-8) rad·Hz(-1/2) and noise-equivalent absorbance (αL)min of 6.27 × 10(-8) Hz(-1/2). White-noise limited performance at 2.8× the shot-noise limit is observed up to ~1000 s, allowing reliable calibration and sample measurement within the drift-free interval of the spectrometer. Integration with wet-chemistry based on acidic vanadium(III) enables conversion of aqueous nitrate/nitrite samples to gaseous NO for total nitrogen isotope analysis. Isotopic ratiometry is accomplished via time-multiplexed measurements of two NO isotope transitions. For 5 μmol potassium nitrate samples, the instrument consistently yields ratiometric precision below 0.3‰, thus demonstrating potential as an in situ diagnostic tool for environmental nitrogen cycle studies.


Anger suppression predicts pain, emotional, and cardiovascular responses to the cold pressor.
Manipulated anger suppression has been shown to heighten pain and anger responses to pain. We examined whether individual differences in self-reported anger suppression predicted pain, anger, and blood pressure responses to acute pain. Healthy participants (N = 47) underwent an anger-provoking speech task followed by a cold pressor pain task. Participants reported their degree of suppression of thoughts and feelings related to the speech. Pain intensity ratings were obtained throughout the cold pressor. Self-reported anger, anxiety and positive emotion, as well as ratings of sensory, general distress, and anger-specific elements of pain were obtained following the cold pressor. Systolic blood pressure (SBP), diastolic blood pressure (DBP), and heart rate (HR) were recorded throughout. Self-reported suppression predicted greater pain intensity ratings, perception of sensory and anger-specific elements of pain, and self-reported anger in response to the cold pressor. Associations between self-reported suppression and pain intensity and ratings of anger-specific elements of pain were statistically mediated by pain-induced changes in self-reported anger, whereas the effect of suppression on sensory pain ratings was not. Self-reported suppression was also correlated inversely with SBP responses to the cold pressor. Consistent with an ironic process model and prior studies involving experimental manipulation of suppression, self-reported suppression of anger predicted greater pain intensity and perception of the anger-specific element of pain. Findings also suggest that suppression might attenuate homeostatic pressor responses to acute pain.


A Smartphone Camera-Based Indoor Positioning Algorithm of Crowded Scenarios with the Assistance of Deep CNN.
Considering the installation cost and coverage, the received signal strength indicator (RSSI)-based indoor positioning system is widely used across the world. However, the indoor positioning performance, due to the interference of wireless signals that are caused by the complex indoor environment that includes a crowded population, cannot achieve the demands of indoor location-based services. In this paper, we focus on increasing the signal strength estimation accuracy considering the population density, which is different to the other RSSI-based indoor positioning methods. Therefore, we propose a new wireless signal compensation model considering the population density, distance, and frequency. First of all, the number of individuals in an indoor crowded scenario can be calculated by our convolutional neural network (CNN)-based human detection approach. Then, the relationship between the population density and the signal attenuation is described in our model. Finally, we use the trilateral positioning principle to realize the pedestrian location. According to the simulation and tests in the crowded scenarios, the proposed model increases the accuracy of the signal strength estimation by 1.53 times compared to that without considering the human body. Therefore, the localization accuracy is less than 1.37 m, which indicates that our algorithm can improve the indoor positioning performance and is superior to other RSSI models.


GC/MS Profiling, Antibacterial, Anti-Quorum Sensing, and Antibiofilm Properties of Anethum graveolens L. Essential Oil: Molecular Docking Study and In-Silico ADME Profiling.
Anethum graveolens L. has been known as an aromatic, medicinal, and culinary herb since ancient times. The main purpose of this study was to determine the chemical composition, antibacterial, antibiofilm, and anti-quorum sensing activities of the essential oil (EO) obtained by hydro-distillation of the aerial parts. Twelve components were identified, representing 92.55% of the analyzed essential oil. Limonene (48.05%), carvone (37.94%), cis-dihydrocarvone (3.5%), and trans-carvone (1.07%) were the main identified constituents. Results showed that the obtained EO was effective against eight bacterial strains at different degrees. Concerning the antibiofilm activity, limonene was more effective against biofilm formation than the essential oil when tested using sub-inhibitory concentrations. The results of anti-swarming activity tested against P. aeruginosa PAO1 revealed that A. graveolens induced more potent inhibitory effects in the swarming behavior of the PAO1 strain when compared to limonene, with a percentage reaching 33.33% at a concentration of 100 µg/mL. The ADME profiling of the identified phytocompounds confirms their important pharmacokinetic and drug-like properties. The in-silico study using molecular docking approaches reveals a high binding score between the identified compounds and known target enzymes involved in antibacterial and anti-quorum sensing (QS) activities. Overall, the obtained results highlight the possible use of A. graveolens EO to prevent food contamination with foodborne pathogenic bacteria.


A Two-Step Haploidentical Versus a Two-Step Matched Related Allogeneic Myeloablative Peripheral Blood Stem Cell Transplantation.
Haploidentical stem cell transplantation (SCT) offers a transplantation option to patients who lack an HLA-matched donor. We developed a 2-step approach to myeloablative allogeneic hematopoietic stem cell transplantation for patients with haploidentical or matched related (MR) donors. In this approach, the lymphoid and myeloid portions of the graft are administered in 2 separate steps to allow fixed T cell dosing. Cyclophosphamide is used for T cell tolerization. Given a uniform conditioning regimen, graft T cell dose, and graft-versus-host disease (GVHD) prophylaxis strategy, we compared immune reconstitution and clinical outcomes in patients undergoing 2-step haploidentical versus 2-step MR SCT. We retrospectively compared data on patients undergoing a 2-step haploidentical (n = 50) or MR (n = 27) peripheral blood SCT for high-risk hematological malignancies and aplastic anemia. Both groups received myeloablative total body irradiation conditioning. Immune reconstitution data included flow cytometric assessment of T cell subsets at day 28 and 90 after SCT. Both groups showed comparable early immune recovery in all assessed T cell subsets except for the median CD3/CD8 cell count, which was higher in the MR group at day 28 compared with that in the haploidentical group. The 3-year probability of overall survival was 70% in the haploidentical group and 71% in the MR group (P = .81), while the 3-year progression-free survival was 68% in the haploidentical group and 70% in the MR group (P = .97). The 3-year cumulative incidence of nonrelapse mortality was 10% in the haploidentical group and 4% in the MR group (P = .34). The 3-year cumulative incidence of relapse was 21% in the haploidentical group and 27% in the MR group (P = .93). The 100-day cumulative incidence of overall grades II to IV acute GVHD was higher in the haploidentical group compared with that in the MR group (40% versus 8%, P < .001), whereas the grades III and IV acute GVHD was not statistically different between both groups (haploidentical, 6%; MR, 4%; P = .49). The cumulative incidence of cytomegalovirus reactivation was also higher in the haploidentical group compared to the MR group (haploidentical, 68%; MR, 19%; P < .001). There were no deaths from GVHD in either group. Using an identical conditioning regimen, graft T cell dose, and GVHD prophylaxis strategy, comparable early immune recovery and clinical outcomes were observed in the 2-step haploidentical and MR SCT recipients.


[Monstrous epithelium in the seminal vesicles and epididymis].
Monstrous epithelial cells in seminal vesicles, causing diagnostical embarrassment , occur sometimes in fine needle-aspirates of prostate gland. Their frequency was studied in a group of autopsies (6 boys of the age from 6 hours to 10 years, mean age 3,1 years and 34 adult men of the age from 42 to 91 years, mean age 68,4 years). Monstrous cells did not occur in boys but were found in 73,5% of adults. There were similar epithelial monstrosities in epididymis simultaneously. Most of them were found in efferent ductuli (in 76,4%). Big monstrous epithelial cells with conspicuous irregular hyperchromatic nuclei are to be distinguished cautiously from the neoplastic ones. They may be caused by ageing and hormonal influence above all (in analogy to Arias-Stella phenomenon in women).


Action-potential-encoded second-harmonic generation as an ultrafast local probe for nonintrusive membrane diagnostics.
The Hodgkin-Huxley treatment of the dynamics of a nerve impulse on a cell membrane is combined with a phenomenological description of molecular hyperpolarizabilities to develop a closed-form model of an action-potential-sensitive second-harmonic response of membrane-bound chromophores. This model is employed to understand the key properties of the map between the action potential and modulation of the second harmonic from a cell membrane stained with hyperpolarizable chromophore molecules.


Pediatric surgical patients' and parents' stress responses and adjustment as a function of psychologic preparation and stress-point nursing care.
The purpose of this study was to test the hypotheses that children who receive systematic psychologic preparation and continued supportive care, in contrast to those who do not, would show less upset behavior and more cooperation in the hospital and fewer post-hospital adjustment problems and that their parents would be less anxious and more satisfied with information and care received. Eighty children scheduled for minor surgery and their parents were randomly assigned to experimental and control conditions. The experimental intervention consisted of accurate information about sequences of events, sensory experiences, role expectations and appropriate responses, previews of procedures through play techniques, and supportive care given at critical points pre- and postoperatively. Significant differences between experimental and control children and parents on ratings of upset behavior, cooperation with procedures, pulse before and after painful procedures, resistance to induction, time to first voiding, posthospital adjustment, and parental anxiety and satisfaction with information and care consistently supported the hypotheses. Results were also analyzed in relation to the age and sex of the children and whether parents roomed with the children.


A high precision, fast response, and low power consumption in situ optical fiber chemical pCO2 sensor.
A sensor system suitable for monitoring changes in partial pressure of carbon dioxide (pCO(2)) in surface seawater or in the atmosphere has been developed. Surface seawater samples are pumped into a PVC tube enclosing an inner Teflon AF tube, which served as a long pathlength gas-permeable liquid-core waveguide for spectrophotometry. The Teflon cell contains a pH-sensitive indicator-buffer solution consisting of bromothymol blue (BTB) and sodium carbonate. Carbon dioxide in the sample diffuses into the indicator-buffer solution to reach equilibrium, resulting in pH changes, which are detected by changes in the absorbance of BTB at wavelengths of 620 and 434 nm. The pCO(2) in the sample is then derived from the pH change. The sensor has a response time of 2 min at the 95% equilibrium value and a measurement precision of 0.26-0.37% in the range 200-800 microatm pCO(2). This chemical sensor takes advantage of a combination of long pathlength, multiple wavelength detection, indicator solution renewal, and in situ automatic control technology, and has the feature of low power consumption (the average being approximately 4 W with a peak of approximately 8 W).


Ziprasidone in treatment-resistant schizophrenia: a 52-week, open-label continuation study.
To evaluate the efficacy, safety, and tolerability of long-term ziprasidone therapy in treatment-resistant schizophrenia. This prospective, 1-year, open-label study of ziprasidone (40-160 mg/day) was conducted in subjects who had participated in a previous randomized 12-week comparison of ziprasi-done and chlorpromazine in treatment-resistant schizophrenia (DSM-III-R criteria). The clinical response of 62 subjects was evaluated (32 subjects had been on ziprasidone treatment and 30 had been on chlorpromazine treatment prior to enrollment in the continuation study). Assessments included the Positive and Negative Syndrome Scale total and subscale scores, movement disorder scales, body weight, and laboratory measures. This study was conducted from May 2000 to April 2002. Thirty-three subjects (53%) completed 1 year of open-label ziprasidone therapy. Ziprasidone maintained clinical improvement (no significant symptom exacerbation) in 30 of 41 subjects (73%) who responded to the initial 12-week double-blind treatment with either ziprasidone or chlorpromazine. Ziprasidone did not increase body weight and was associated with a favorable metabolic profile during the continuation study period. There were no significant changes in standard movement disorder measures from the core study baseline during long-term ziprasidone treatment. Ziprasidone was effective and well tolerated in the long-term therapy of patients with treatment-resistant schizophrenia.


Abdominal actinomycosis in the last 10 years and risk factors for appendiceal actinomycosis: review of the literature.
Actinomycosis is a granulomatous disease caused by filamentous, gram-positive, anaerobic bacteria. Actinomycetes are commensal inhabitants of the oral cavity and intestinal tract but acquire pathogenicity through invasion of breached or necrotic tissue.1397645907In abdominal actinomycosis (AA), the appendix and ileocecal region are usually involved. The aim of this study was to characterize patients diagnosed with AA and to establish the risk factors for appendiceal actinomycosis, including a short review of the literature. We conducted a prospective cohort study of all patients diagnosed with AA in the University Hospital Marques de Valdecilla (Santander-Cantabria) from January 2003 to October 2013. We also conducted a short review of the literature. We characterized the epidemiological features of patients diagnosed with AA and risk factors for the involvement of the appendix, as most of the cases were misdiagnosed as appendicitis. Risk factors for appendiceal actinomycosis are no antecedents of carcinoma (P = 0.034) and previous incorrect diagnosis (P = 0.006). AA is a rare and chronic infection. It is only reported in case reports in the literature. We present the largest series of patients diagnosed with AA. Half of the patients had morbidities, mostly carcinoma, and penicillin was the preferred treatment. More studies are needed to characterize patients affected with AA and to establish the correct treatment.


A potato mitochondrial isoleucine tRNA is coded for by a mitochondrial gene possessing a methionine anticodon.
The nucleotide sequence of a potato mitochondrial tRNA(Ile) has been determined. This tRNA has a lysidine-like minor nucleotide in the first position of the anticodon (position 34). The corresponding mitochondrial gene has been cloned and sequenced. This gene has a CAT anticodon which corresponds to methionine. The C residue in the anticodon must therefore be post-transcriptionally modified. The mature tRNA has isoleucine-accepting activity but no methionine-accepting activity. This is the first report showing that in plant mitochondria a post-transcriptional modification could change the amino-acid specificity of a tRNA, as compared to that of the corresponding gene.


[Quality of life with genital herpes].
Health related quality of life (HRQOL) indicators take into account the personal perception of health, and are proposed as an alternative for efficacy indicators in medical and therapeutic decision-making. They provide, after elaboration and validation of a questionnaire, a standardized assessment of the health status perception. The authors had for aim to review of a variety of HRQOL instruments developed for patients presenting with genital herpes infection. Generic instruments are designed to be applicable in general population and disease-targeted instrument are potentially more sensitive to the characteristics of a specific population. Among HRQOL instruments, we found 4 specific disease-targeted questionnaires developed for patients presenting with genital herpes infection: Genital herpes questionnaire, Herpes research center questionnaire, quality of life with herpes (QLH) scale, and recurrent genital herpes quality of life (RGHQoL).


[The intensive care gallbladder as shock organ: symptoms and therapy].
Acute acalculous cholecystitis (AAC) represents a severe disease in critically ill patients. The pathogenesis of acute necroinflammatory gallbladder disease is multifactorial and intensive care unit (ICU) patients show multiple risk factors. In addition AAC is difficult to diagnose because of the vague physical and non-specific technical findings. Only the combination of clinical and technical findings including the challenging physical examination of critically ill patients, laboratory results and ultrasound or computed tomography (CT) scan, will lead to the diagnosis. The condition of AAC has a rapid progress to gallbladder necrosis, gangrene and perforation and these complications are reflected in the high morbidity and mortality rates, therefore, therapy should be promptly initiated. If there are no clinical contraindications for an operative approach cholecystectomy is the definitive treatment and both open and laparoscopic procedures have been used. In unstable, critically ill patients percutaneous cholecystostomy should be immediately performed. In addition, transpapillary endoscopic drainage is also possible if there are contraindications for percutaneous cholecystostomy. Patients who fail to improve or deteriorate following interventional drainage should be reconsidered for cholecystectomy. Due to the fact that more than 90 % of patients treated with percutaneous cholecystostomy showed no recurrence of symptoms during a period of more than 1 year, it is still unclear if percutaneous cholecystostomy is the definitive treatment of AAC for unstable patients or if delayed cholecystectomy is still necessary.


High-level iron mitigates fusaricidin-induced membrane damage and reduces membrane fluidity leading to enhanced drug resistance in Bacillus subtilis.
Fusaricidins are a class of cyclic lipopeptide antibiotics that have strong antifungal activities against plant pathogenic fungi and excellent bactericidal activities against Gram-positive bacteria. The mechanism through which fusaricidin exerts its action is not yet entirely clear. To investigate the mode of action of fusaricidin, we determined the physiological and transcriptional responses of Bacillus subtilis to fusaricidin treatment by using a systems-level approach. Our data show that fusaricidin rapidly induced the expression of σ(W) regulon and caused membrane damage in B. subtilis. We further demonstrated that ferric ions play multiple roles in the action of fusaricidin on B. subtilis. Iron deprivation blocked the formation of hydroxyl radical in the cells and significantly inhibited the bactericidal activity of fusaricidin. Conversely, high levels of iron (>2 mM) repressed the expression of BkdR regulon, resulting in a smaller cellular pool of branched-chain precursors for iso- and anteiso-branched fatty acids, which in turn led to a decrease in the proportion of branched-chain fatty acids in the membrane of B. subtilis. This change in membrane composition reduced its bilayer fluidity and increased its resistance to antimicrobial agents. In conclusion, our experiments uncovered some novel interactions and a synergism between cellular iron levels and drug resistance in Gram-positive bacteria.


[Cerebral edema: intra-cellular or extra-cellular mechanisms?].
Many cerebral pathological processes are attended by edema defined as an increase in brain volume associated with an increase in brain water and sodium contents. The aggravation of lesions induced by this edema warrants a pharmacological and therapeutic approach based on a detailed knowledge of its physiopathological mechanisms. Experimental models and in vitro studies have shown that the fundamental mechanisms leading to edema are: cold, acute hypoxia, ischaemia, arachidonic acid, toxic substances and plasma hypo-osmolarity. To the various types of edema described (vasogenic, cytotoxic, hydrocephalic) correspond different mechanisms. Vasogenic edema essentially depends on osmotic and hydrodynamic factors; cytotoxic edema results from perturbations in energy-dependent cellular osmoregulation. The underlying biochemical disorders have now been demonstrated, mostly in ischaemic edema; they include, during the revascularization phase, disruption of the blood-brain barrier (vasogenic component) and changes in ion concentrations, neurotransmitters and energetic mechanisms. Key factors in the development of edema are cyclic AMP, serotonin and Na-K-ATPase.


Fabrication of volcano-shaped nano-patterned sapphire substrates using colloidal self-assembly and wet chemical etching.
Patterned sapphire substrates (PSS) have been widely used to enhance the light output power in GaN-based light emitting diodes. The shape and feature size of the pattern in a PSS affect its enhancement efficiency to a great degree. In this work we demonstrate the nanoscale fabrication of volcano-shaped PSS using a wet chemical etching approach in combination with a colloidal monolayer templating strategy. Detailed analysis by scanning electron microscopy reveals that the unique pattern shape is a result of the different corrosion-resistant abilities of silica masks of different effective heights during wet chemical etching. The formation of silica etching masks of different effective heights has been ascribed to the silica precursor solution in the interstice of the colloidal monolayer template being distributed unevenly after infiltration. In the subsequent wet chemical etching process, the active reaction sites altered as etching duration was prolonged, resulting in the formation of volcano-shaped nano-patterned sapphire substrates.


A Developmental Perspective on Peer Rejection, Deviant Peer Affiliation, and Conduct Problems Among Youth.
Peer rejection and deviant peer affiliation are linked consistently to the development and maintenance of conduct problems. Two proposed models may account for longitudinal relations among these peer processes and conduct problems: the (a) sequential mediation model, in which peer rejection in childhood and deviant peer affiliation in adolescence mediate the link between early externalizing behaviors and more serious adolescent conduct problems; and (b) parallel process model, in which peer rejection and deviant peer affiliation are considered independent processes that operate simultaneously to increment risk for conduct problems. In this review, we evaluate theoretical models and evidence for associations among conduct problems and (a) peer rejection and (b) deviant peer affiliation. We then consider support for the sequential mediation and parallel process models. Next, we propose an integrated model incorporating both the sequential mediation and parallel process models. Future research directions and implications for prevention and intervention efforts are discussed.


Comparison of Measured and Monte Carlo Calculated Dose Distributions from Indigenously Developed 6 MV Flattening Filter Free Medical Linear Accelerator.
Monte Carlo simulation was carried out for a 6 MV flattening filter-free (FFF) indigenously developed linear accelerator (linac) using the BEAMnrc user-code of the EGSnrc code system. The model was benchmarked against the measurements. A Gaussian distributed electron beam of kinetic energy 6.2 MeV with full-width half maximum of 1 mm was used in this study. The simulation of indigenously developed linac unit has been carried out by using the Monte Carlo-based BEAMnrc user-code of the EGSnrc code system. Using the simulated model, depth and lateral dose profiles were studied using the DOSXYZnrc user-code. The calculated dose data were compared against the measurements using an RFA dosimertic system made by PTW, Germany (water tank MP3-M and 0.125 cm3 ion chamber). The BEAMDP code was used to analyze photon fluence spectra, mean energy distribution, and electron contamination fluence spectra. Percentage depth dose (PDD) and beam profiles (along both X and Y directions) were calculated for the field sizes 5 cm × 5 cm - 25 cm × 25 cm. The dose difference between the calculated and measured PDD and profile values were under 1%, except for the penumbra region where the maximum deviation was found to be around 3%. A Monte Carlo model of indigenous FFF linac (6 MV) has been developed and benchmarked against the measured data.


Use of implantable cardioverter-defibrillators in pediatric patients.
Automatic implantable cardioverter-defibrillator use has become widespread in the prevention of sudden death in at-risk populations. The compelling safety and efficacy data in numerous large, blinded trials on adult patients have led to increasing use of these devices in pediatric patients. Although there are no prospective data to support device therapy in pediatric patients, several large, retrospective studies suggest that pediatric patients are likely to enjoy the same reduction in mortality as adult patients, with a slightly higher rate of complications from the device implant. Data on the use of these devices in pediatric patients for several different indications exist but are limited to retrospective reviews with small numbers and short follow-up. Large prospective trials are needed to assess the safety and efficacy of these devices in children and the influence of implant technique, patient growth, and programmed parameters on overall outcome.


Surgical treatment of vertigo.
Surgical therapy for disabling vertigo usually comes in at a late stage in the course of treatment for this patient group. The surgical procedures can be divided into two categories: non-destructive and destructive surgery. The former constitutes primarily procedures directed against the endolymphatic sac such as endolymphatic sac shunt procedures or decompression procedures. Peri-endolymphatic shunt procedures have also been proposed by some surgeons. None of these latter procedures have, however, gained widespread clinical acceptance. Destructive surgery is aimed against the end-organ itself or the vestibular nerve. Labyrinthectomy entails ablation of the vestibular end organs. This procedure is advocated in patients with disabling vertigo and a severe hearing loss or total deafness in the affected ear. Vestibular neurectomy can be performed at different levels. The middle fossa approach allows visualization of the vestibular nerve inside the internal auditory canal, whereas the retrolabyrinthine approach reveals the course of the nerves in the posterior cranial fossa. Vestibular neurectomy offers good results in the hands of a trained otoneurosurgeon.


Treatment and management of liver diseases by Khmer traditional healers practicing in Phnom Penh area, Cambodia.
Liver disorders are a major health problem in Cambodia, where some patients prefer to seek treatment from traditional healers. The aim of the study was to document the knowledge and practices of these healers in four Southern Cambodian provinces. An ethnopharmacological survey was carried out from September 2015 to January 2016 in Cambodian urban and rural areas. Thirty-three Khmer traditional healers (KTH) were interviewed using a semi-structured questionnaire including socio-demographic data, healer's formation and their professional practice conditions, perception of liver diseases (types and causes of liver disorders, diagnostic methods and symptoms of liver problems), dietary recommendations given to patients, and herbal remedies used to treat them. For each medicinal plant mentioned in herbal remedies, the local name, part of the plant, mode of preparation and administration, and their properties, according to the healers, were recorded. The plants mentioned by the traditional therapists were collected and later identified by specialists. Different types of liver disease are identified by the healers, and diagnosis was mostly based on reading medical records, and by observing the yellow discoloration of the skin and eyes. A total of 42 herbal remedies including 83 medicinal plants belonging to 40 families were mentioned for treating liver disorders. The most predominant families were Leguminosae and Poaceae. Among the plants reported, Cananga latifolia, Andrographis paniculata, Smilax aff. glabra, Gomphrena celosioides, Passiflora foetida and Physalis minima were the most cited species. A large part of the herbal remedies used were multi-ingredient recipes, and were prepared mainly by a decoction administered orally. Plants are combined in multi-ingredient recipes, and selected on the basis of their properties (trocheak, psah, somrap mé rok, ktchol) which originate from Khmer medical concepts. Most of the plants used by healers have a wide ethnobotanical use for liver disorders, and have been studied for their hepatoprotective activity and related activities on the liver. In the diagnosis and treatment of liver diseases, KTH have incorporated biomedical concepts and new practices, which suggest that they could be defined as neotraditional healers. Medicinal plants constitute the core of traditional medicine practice by these healers, and these plants play a very important role in the health care of people with liver problems in Cambodia. Therefore, more attention should be paid to the integration of healers in national health care programs for the development of combined therapies. Furthermore, two plant species (i.e. Cananga latifolia and Willughbeia edulis) were found to be widely used for treating liver disorders in our survey, and should be studied for their pharmacological potential for liver problems.


Challenges and demands in the population-based work of public health nurses.
Government programs and the Norwegian Directorate of Health give public health nurses in Norway an explicit role in population-based health promotion and disease-prevention work. The aim of this paper is to explore Norwegian public health nurses' experiences with population-based work. A phenomenological hermeneutic approach was adopted, involving face-to-face interviews with a purposeful sample of 23 public health nurses from urban and rural districts in two counties in Norway. Three themes were identified: the predominance of work at the individual level, a lack of resources, and adherence to administrative directives. The interviews revealed that the public health nurses were mostly occupied with individual problem-solving activities. Population-based work was hardly prioritized, mostly because of a lack of resources and a lack of recognition of the population-based role of public health nurses. The study indicates contradictions between the public health nursing practice related to population-based work and the direction outlined by the government and the public health nursing curriculum, which may mean that the public health nursing role is not sufficiently clarified. The implementation of practice models and administrative directives and resources, as well as an explicit emphasis on population health in public health nursing education, can contribute to increased population-based interventions. Greater knowledge of and emphasis on population-based work in public health nursing are needed.


High risk prostate cancer: evolving definition and approach to management.
Advances in the early detection and treatment of prostate cancer have progressed far beyond our ability to identify patients with high risk prostate cancer. In general, designation of high risk prostate cancer implies the presence of disease that is likely become progressive or lethal if not managed aggressively. Without proper risk stratification, there is a significant likelihood of both overtreatments of men with low risk disease and undertreatment for men with high risk cancer. The major issues surrounding the clinical management of high risk prostate cancer revolve around the definition of high risk disease as well as the benefits of multiple modality therapy. Over the years, numerous attempts have been made to develop risk assessment tools such as risk categories, scoring systems and nomograms, but a widely accepted definition is yet to be determined. The benefits of routine clinical utility of these risk assessment tools remain somewhat difficult to ascertain. We will discuss several multimodality therapeutic approaches, especially in combination with androgen ablation, to improve the outlook for men with high risk or locally advanced prostate cancer. This review focuses on the potential limitations of the risk assessment tools available to the clinicians and the approach to management of high risk prostate cancer.


Serum interleukin-4 is elevated in clinical drug-induced liver injury.
Drug-induced liver injury (DILI) remains a challenging diagnosis due to an absence of specific biomarkers. DILI due to volatile anaesthetics (VA-DILI) is characterised by trifluoroacetyl and CYP2E1 antibodies, but may not be seen for weeks after injury. Interleukin-4 (IL-4) may be involved in the production of these antibodies and may serve as a clinically useful early biomarker of VA-DILI. To prospectively compare serum IL-4 levels between patients who develop VA-DILI and controls following exposure to the volatile anaesthetic. A nested case-control study of patients exposed to VA during surgery was conducted. Thirteen DILI cases were identified from the original cohort, and 26 controls were matched according to age, sex and VA agent. Serum samples were collected before and 48-96 h after VA exposure, and analysed for IL-4 using quantitative enzyme-linked immunosorbent assay techniques. There was a statistically significant difference in serum IL-4 in post-VA samples between DILI cases and controls (control: 0.030 pg/mL, IQR: 0.030 - 0.030 pg/mL vs DILI: 0.044 pg/mL, IQR: 0.030 - 0.061 pg/mL; p = 0.039). A greater proportion of DILI cases had post-VA IL-4 levels above the assay lower limit of detection compared to controls (control: 23% vs DILI: 69%; p = 0.013). IL-4 is a potential biomarker of DILI. Clinical diagnosis and understanding of DILI disease mechanisms may be improved by further investigation of novel biomarkers, and this IL-4 signal in serum is important as proof of concept for prospective study designs.


Spin Hall and spin Nernst effects due to intrinsic spin-orbit coupling in monolayer and bilayer graphene.
We consider intrinsic contributions to the spin Hall and spin Nernst effects in monolayer and bilayer graphene. The spin Hall (Nernst) effect consists in the generation of transverse spin current by longitudinal electric field (temperature gradient). The relevant electronic spectrum for monolayer and bilayer graphene has been obtained from the corresponding effective Hamiltonians. Both spin Hall and spin Nernst conductivities have been determined within the linear response theory and Green function formalism. The influence of an external vertical voltage between the two atomic sheets in the case of a bilayer graphene is also analyzed and discussed. This voltage can generally lead to a phase transition between the topological insulator phase and conventional insulator. In the case of bilayer graphene, the main focuss is on an asymmetrical case, with different spin-orbit parameters in the two atomic sheets. Such a difference may be generated by different atomic planes adjacent to bilayer graphene on its both sides.