Corrigenda to Gil-Santana, H.R. 2018. A new species of Phasmatocoris from French Guiana, with short taxonomic notes on two described species and an updated key (Hemiptera: Heteroptera: Reduviidae: Emesinae). Zootaxa 4413 (3): 491-506.
An intraspecific variation of the male genitalia of Phasmatocoris papei Gil-Santana, 2018 (Hemiptera: Heteroptera: Reduviidae: Emesinae: Emesini), i.e., the absence (holotype) / presence (paratype) of the sclerotization of approximately basal two thirds of the ventral wall of phallosoma, reported by Gil-Santana (2018), was found to be incorrect. A subsequent reexamination of the specimens revealed that the misjudgement was based on a breakage of this structure in the phallus of the holotype. In fact, the ventral wall of phallosoma was completely sclerotized at its basal two-thirds in both specimens and should be considered as a species level character of Ph. papei.


Distribution of peripheral blood cells after splenectomy in immune thrombocytopenia patients.
There are some difficulties regarding the evaluation of the post-splenectomy state. The objective of the study is to compare the post-splenectomy blood changes of immune thrombocytopenia (ITP) patients with those of trauma patients, 1 month and ≥ 6 months after surgery. Medical records of patients, who had undergone total splenectomy for ITP and trauma at a tertiary center between January 2009 and December 2019, were retrospectively reviewed. The current study included 52 patients, who had undergone splenectomy for ITP (57.7%), and trauma (42.3%). Splenectomy, irrespective of the indications, resulted in an increase in hemoglobin concentration, hematocrit, and platelet levels. Neutrophils were responsible for the preoperative leukocytosis in ITP patients, and neutrophilia was ameliorated by splenectomy and also withdrawal of the steroid therapy in some patients. Decreased neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio supported the finding that splenectomy ameliorated inflammation in ITP patients. Splenectomy resulted in a change in percentages of leukocytes in favor of basophils in ITP patients. Splenectomy, irrespective of the indications, resulted in an increase in hemoglobin concentration, hematocrit and platelet levels, lymphocyte, monocyte, and eosinophil counts. Splenectomy ameliorated inflammation in ITP patients and resulted in a change in percentages of leukocytes in favor of basophils.


Opinions of constraint-induced movement therapy among therapists in southwestern Ohio.
To determine the opinions of therapists about constraint-induced movement therapy (CIMT). A convenience sample of 92 therapists with at least 1 year of clinical experience working in outpatient and inpatient hospital and clinical neurorehabilitation settings was surveyed. Subjects completed a self-report questionnaire discerning their opinions of CIMT during their clinical staff meetings. The questionnaire described CIMT to participants using excerpts from a recently published trial of CIMT. Subjects then responded to various statements concerning their opinions of the protocol and supplied the rationale for their opinions. Seventy-five percent of participants reported that it would be very difficult or difficult to administer CIMT in their clinics, and 83% felt that most clinics would not have the resources to implement CIMT. Additionally, more than 61% of respondents stated that managed care payers were either somewhat unlikely or very unlikely to reimburse for CIMT, and no respondent believed that it was very likely that managed care would fund CIMT. Most respondents felt that patients would experience great difficulty with the clinical session and restrictive device durations. There were 78.3% of participants who were not aware that an efficacious modified CIMT regimen was available that could overcome the aforementioned challenges. Findings were consistent with CIMT trials and surveys regarding client compliance difficulties and therapist misgivings. Findings argue for continued refinement of modified CIMT regimens as well as greater educational efforts regarding CIMT for therapists.


L-Selectin/CD62L is a Key Driver of Non-Alcoholic Steatohepatitis in Mice and Men.
CD62L (L-Selectin) dependent lymphocyte infiltration is known to induce inflammatory bowel disease (IBD), while its function in the liver, especially in non-alcoholic steatohepatitis (NASH), remains unclear. We here investigated the functional role of CD62L in NASH in humans as well as in two mouse models of steatohepatitis. Hepatic expression of a soluble form of CD62L (sCD62L) was measured in patients with steatosis and NASH. Furthermore, CD62L-/- mice were fed with a methionine and choline deficient (MCD) diet for 4 weeks or with a high fat diet (HFD) for 24 weeks. Patients with NASH displayed increased serum levels of sCD62L. Hepatic CD62L expression was higher in patients with steatosis and increased dramatically in NASH patients. Interestingly, compared to wild type (WT) mice, MCD and HFD-treated CD62L-/- mice were protected from diet-induced steatohepatitis. This was reflected by less fat accumulation in hepatocytes and a dampened manifestation of the metabolic syndrome with an improved insulin resistance and decreased cholesterol and triglyceride levels. Consistent with ameliorated disease, CD62L-/- animals exhibited an enhanced hepatic infiltration of Treg cells and a strong activation of an anti-oxidative stress response. Those changes finally resulted in less fibrosis in CD62L-/- mice. Additionally, this effect could be reproduced in a therapeutic setting by administrating an anti-CD62L blocking antibody. CD62L expression in humans and mice correlates with disease activity of steatohepatitis. CD62L knockout and anti-CD62L-treated mice are protected from diet-induced steatohepatitis suggesting that CD62L is a promising target for therapeutic interventions in NASH.


The nuclear PP1 interacting protein ZAP3 (ZAP) is a putative nucleoside kinase that complexes with SAM68, CIA, NF110/45, and HNRNP-G.
The targeting of protein kinases and phosphatases is fundamental to their roles as cellular regulators. The type one serine/threonine protein phosphatase (PP1) is enriched in the nucleus, yet few nuclear PP1 targeting subunits have been described and characterized. Here we show that the human protein, ZAP3 (also known as ZAP), is localized to the nucleus, that it is expressed in all mammalian tissues examined, and docks to PP1 through an RVRW motif located in its highly conserved carboxy-terminus. Proteomic analysis of a ZAP3 complex revealed that in addition to binding PP1, ZAP3 complexes with CIA (or nuclear receptor co-activator 5) and the RNA binding proteins hnRNP-G, SAM68 and NF110/45, but loses affinity for SAM68 and hnRNP-G upon digestion of endogenous nucleic acid. Bioinformatics has revealed that the conserved carboxy-terminus is orthologous to T4- and mammalian polynucleotide kinases with residues necessary for kinase activity maintained throughout evolution. Furthermore, the substrate binding pocket of uridine-cytidine kinase (or uridine kinase) has localized sequence similarity with ZAP3, suggesting uridine or cytidine as possible ZAP3 substrates. Most polynucleotide kinases have a phosphohydrolase domain in conjunction with their kinase domain. In ZAP3, although this domain is present, it now appears degenerate and functions to bind PP1 through an RVRW docking site located within the domain.


Long Noncoding RNAs in Neurodegenerative Diseases: Pathogenesis and Potential Implications as Clinical Biomarkers.
Neurodegenerative diseases (NDDs), including Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and amyotrophic lateral sclerosis (ALS), are progressive and ultimately fatal. NDD onset is influenced by several factors including heredity and environmental cues. Long noncoding RNAs (lncRNAs) are a class of noncoding RNA molecules with: (i) lengths greater than 200 nucleotides, (ii) diverse biological functions, and (iii) highly conserved structures. They directly interact with molecules such as proteins and microRNAs and subsequently regulate the expression of their targets at the genetic, transcriptional, and post-transcriptional levels. Emerging studies indicate the important roles of lncRNAs in the progression of neurological diseases including NDDs. Additionally, improvements in detection technologies have enabled quantitative lncRNA detection and application to circulating fluids in clinical settings. Here, we review current research on lncRNAs in animal models and patients with NDDs. We also discuss the potential applicability of circulating lncRNAs as biomarkers in NDD diagnostics and prognostics. In the future, a better understanding of the roles of lncRNAs in NDDs will be essential to exploit these new therapeutic targets and improve noninvasive diagnostic methods for diseases.


[Anisakids and human anisakiasis. 1. Bibliographic data].
Currently available data about larvae of Anisakidae (genera Anisakis, Pseudoterranova, Hysterothylacium and Contracaecum) from marine fishes are analysed. Hazard of such parasites for fish-consumers are emphasized.


Pancreatic cancer and retroperitoneal neural tissue invasion. Its implication for survival following radical surgery.
To analyze the implication of retroperitoneal perineural lymphatic infiltration (rpli) for the survival of patients affected by exocrine pancreatic cancer, we considered 17 cases which underwent radical resection at our Institute from 1980 to 1993. Histology of specimens showed an rpli in 15 cases, without any correlation between this anatomopathologic aspect and the neoplasm size or the presence of lymph node metastases. The 2 patients without rpli are both alive and have been free from disease during a follow-up period of more than 5 years. In the group of 15 patients with positive rpli, 3 (21.4%) have remained free from disease (2 alive and 1 dead for other reason). Eleven remained with disease (1 is alive and 10 have died). One died in the postoperative period and could not be included in the evaluation. These observations have led the surgeon to consider the necessity, during resection, of an accurate dissection not only of the regional lymph nodes but also of the retropancreatic tissue and the neural structures present in this area. This approach may lead to a more correct staging of the neoplasia, a better radical surgery and perhaps a longer survival. Moreover it may represent an important marker for an adjuvant protocol of chemotherapy and/or radiotherapy.


Azetidinic amino acids: stereocontrolled synthesis and pharmacological characterization as ligands for glutamate receptors and transporters.
A set of ten azetidinic amino acids, that can be envisioned as C-4 alkyl substituted analogues of trans-2-carboxyazetidine-3-acetic acid (t-CAA) and/or conformationally constrained analogues of (R)- or (S)-glutamic acid (Glu) have been synthesized in a diastereo- and enantiomerically pure form from beta-amino alcohols through a straightforward five step sequence. The key step of this synthesis is an original anionic 4-exo-tet ring closure that forms the azetidine ring upon an intramolecular Michael addition. This reaction was proven to be reversible and to lead to a thermodynamic distribution of two diastereoisomers that were easily separated and converted in two steps into azetidinic amino acids. Azetidines 35-44 were characterized in binding studies on native ionotropic Glu receptors and in functional assays at cloned metabotropic receptors mGluR1, 2 and 4, representing group I, II and III mGlu receptors, respectively. Furthermore, azetidine analogues 35, 36, and 40 were also characterized as potential ligands at the glutamate transporter subtypes EAAT1-3 in the FLIPR Membrane Potential (FMP) assay. The (2R)-azetidines 35, 37, 39, 41 and 43 were inactive in iGlu, mGlu and EAAT assays, whereas a marked change in the pharmacological profile at the iGlu receptors was observed when a methyl group was introduced in the C-4 position, compound 36 versus t-CAA. At EAAT1-3, compound 35 was inactive, whereas azetidines 36 and 40 were both identified as inhibitors and showed selectivity for the EAAT2 subtype.


Assaults against general practitioners in Ireland.
Violence directed at general practitioners (GPs) is on the increase in urban areas of Ireland. However, little information has been available on the incidence, effects, or precipitants of this violence. This study documents the frequency of the problem in Ireland's capital city, Dublin. A survey was sent to all 634 GPs in the Eastern Health Board region of Ireland. The survey asked each GP to report an incident of violence or aggression using standardized definitions and reporting forms. The survey also requested that participants provide information on their practice and its staff and setting. We collected information from 622 of 634 doctors (98%). The overall incidence of violence or aggression in the sample was 21%. Of the 131 incidents reported, only 7% resulted in injury to the doctor; the remainder all involved verbal abuse and/or threats. The most frequent assailant characteristics identified were alcohol or opiate abuse. Violence and aggression against GPs are common. Several interventions are discussed.


Genetic diversity and phylogeography of Siberian roe deer, Caproulus pygargus, in central and peripheral populations.
Current understanding of phylogeographical structure and genetic diversity of Siberian roe deer remains limited mainly due to small sample size and/or low geographical coverage in previous studies. Published data suggest at least two phylogroups: western (Ural Mountains and Western Siberia) and eastern (east from lake Baikal, including the Korean peninsula), but their phylogenetic relationship remains unclear. Combined sequences of cytochrome b (1140 bp) and the mtDNA control region (963 bp) were analyzed from 219 Siberian roe deer from 12 locations in Russia, Mongolia, and South Korea, which cover a large part of its range, to assess genetic diversity and phylogeographical status. Special emphasis was placed on the demographic history and genetic features of central, peripheral, and isolated populations. Results of median-joining network and phylogenetic tree analyses indicate that Siberian roe deer from the Urals to the Pacific Ocean are genetically diverse and that geographical distribution and composition of haplogroups coincide with previously described ranges of the subspecies Capreolus pygargus pygargus and Capreolus pygargus tianschanicus. We found that peripheral populations in the northwestern parts of the species range (Urals), as well as the isolated population from Jeju Island, are genetically distinct from those in the core part of the range, both in terms of genetic diversity and quantitative composition of haplogroups. We also found that northwestern (Urals) and northern (Yakutia) peripheral populations share the same haplogroup and fall into the same phylogenetic clade with the isolated population from Jeju Island. This finding sheds light on the taxonomic status of the Jeju Island population and leads to hypotheses about the discordance of morphological and genetic evolution in isolated populations and specific genetic features of peripheral populations.


Experimental Warming Has Not Affected the Changes in Soil Organic Carbon During the Growing Season in an Alpine Meadow Ecosystem on the Qinghai-Tibet Plateau.
The effects of climate warming and season on soil organic carbon (SOC) have received widespread attention, but how climate warming affects the seasonal changes of SOC remains unclear. Here, we established a gradient warming experiment to investigate plant attributes and soil physicochemical and microbial properties that were potentially associated with changes in SOC at the beginning (May) and end (August) of the growing season in an alpine meadow ecosystem on the Qinghai-Tibet Plateau. The SOC of August was lower than that of May, and the storage of SOC in August decreased by an average of 18.53 million grams of carbon per hectare. Warming not only failed to alter the content of SOC regardless of the season but also did not affect the change in SOC during the growing season. Among all the variables measured, microbial biomass carbon was highly coupled to the change in SOC. These findings indicate that alpine meadow soil is a source of carbon during the growing season, but climate warming has no significant impact on it. This study highlights that in the regulation of carbon source or pool in alpine meadow ecosystem, more attention should be paid to changes in SOC during the growing season, rather than climate warming.


Determination of Organophosphorous Pesticides in Blood Using Microextraction in Packed Sorbent and Gas Chromatography-Tandem Mass Spectrometry.
The aim of our work was to develop a method for the determination of six organophosphorous pesticides (Ops) (azynphos-ethyl (AZP), diazinon (DZN), chlorpyrifos (CLP), chlorfenvinfos (CLF), parathion-ethyl (PRT) and quinalphos (QLP)) in whole blood using microextraction by packed sorbent (MEPS) and analysis by gas chromatography-tandem mass spectrometry (GC-MS/MS). The optimization of the MEPS procedure was performed using a design of experiments (DOE) approach, assessing different factors that significantly affected the extraction efficiency. Ultimately, the number of sample strokes, wash volume, percentage of 2-propanol in the wash solvent and the number of elution strokes were successfully optimized using a response surface methodology (RSM). The developed and optimized method was fully validated according to international guidelines. Linearity was established from 2.5 to 50 μg/mL for AZP and from 0.5 to 50 μg/mL for the remaining compounds, with coefficients of determination (R2) higher than 0.99 in all cases. The lower limit of quantification were 2.5 μg/mL (AZP) and 0.5 μg/mL (remaining compounds). Recoveries ranged from 61% to 77%. Intra- and inter-day precision and accuracy were considered adequate according to the guidelines. This is the first method employing MEPS as a sample preparation procedure for the analysis of these OPs in whole blood.


Type 1 Kounis Syndrome in Patient with Idiopathic Anaphylaxis.
Kounis syndrome represents the concurrence of acute coronary syndromes or anginal pain with allergic, hypersensitivity, and anaphylactic reactions. It can be associated with normal coronary angiogram or preexistent coronary pathology. Idiopathic anaphylaxis is defined as anaphylaxis without any identifiable precipitating agent or event. We present a case of male who experienced attacks of dyspnoea, hypoxemia, hypotension, purple-red skin, and chest pain over several years. He was diagnosed with idiopathic anaphylaxis. Based on the pattern of chest pain of ischemic origin during the attacks he was retrospectively diagnosed with Kounis syndrome.


Microbial communities in sandy beaches from the three domains of life differ by microhabitat and intertidal location.
The microbial communities of sandy beaches are poorly described despite the biogeochemical importance and ubiquity of these ecosystems. Using metabarcoding of the 16S and 18S rRNA genes, we investigated the diversity, microhabitats (with or between sand grains) and intertidal distributions of microorganisms (including meiofauna) from pristine sandy beaches in British Columbia, Canada, and hypothesized that abiotic variations due to microhabitat or intertidal gradients influence the distribution of microorganisms on local scales. Bacterial, archaeal and protistan communities of the sand were clearly distinct from interstitial communities, and from planktonic communities of the overlying seawater, which correlated with differences in function and lifestyle (e.g., sulphur reduction and gliding motility). In contrast, meiofaunal communities could not be distinguished by sample type, suggesting that they are more frequently mobilized between these microhabitats. Across intertidal zones, high intertidal, mid intertidal and low intertidal/swash communities were distinct and correlated with moisture, organic carbon and phosphate content, implying that the distribution of microorganisms is influenced by intertidal abiotic gradients. However, few taxa at the genus or species level individually contributed to this zonation pattern; rather, a unique combination of multiple microbial taxa was probably responsible. Although significant differences in microbial community composition on sandy beaches can be attributed to microhabitat and intertidal gradients, further investigations are needed to assess community assembly processes, the consistency of these distributions, and the functions of the majority of the microorganisms observed in the sand and their effects on the biogeochemistry and ecology of sandy beaches.


Advancing Gerontological Health Research With Sexual and Gender Minorities Across the Globe.
The current article presents results of a scoping review of international research on the health and health care needs of sexual and gender minority (SGM) older adults. Electronic databases and related resources were used to identify empirical and review studies published during the past 10 years. We reviewed 33 peer-reviewed articles from 19 countries. Findings were organized using the SGM Health Disparities Research Framework, which highlights factors at individual, interpersonal, community, and societal levels that impact health. Overall, historic and current environmental factors, including stigma, discrimination, and social exclusion, played an important role in SGM older adults' health, health care access, and use of related aging and social services. There is a critical need for training and future research, and health professionals are needed to advance gerontological health and health care research and improve the health and care of SGM older adults globally. [Journal of Gerontological Nursing, 48(4), 13-20.].


Successful use of granulocyte colony-stimulating factor to correct neutropenia in chronic lymphocytic leukaemia.
A case of wound infection secondary to profound neutropenia associated with chronic lymphocytic leukaemia is described. Both the neutropenia and infection resolved with the use of granulocyte colony-stimulating factor. This agent may be useful in other similar patients.


The Influence of Arthroscopic Shaver Mincing and Platelet-Rich Plasma on Chondrocytes of Intraoperatively Harvested Human Cartilage.
Minced cartilage implantation (MCI) has seen a renaissance in recent years. In this evolved technique, human articular cartilage is harvested with an arthroscopic shaver, augmented with platelet-rich plasma (PRP), and implanted with autologous thrombin. This modified technique combines the possibility of cell-based surgical cartilage repair with a minimally invasive autologous 1-step procedure. However, evidence on cell survival and preserved function after shaver-based mincing and PRP supplementation is limited. To evaluate the effects of arthroscopic shaver mincing and augmentation with PRP on human cartilage tissue. Controlled laboratory study. Standardized samples were taken from 12 donors during autologous MCI. A comparison of cell outgrowth, cell viability, proliferation capacity, and ability to produce extracellular matrix-specific proteoglycans after chondrogenic redifferentiation was made between cartilage taken by curettage from the border of the cartilage defect, cartilage tissue minced by an arthroscopic shaver, and cartilage tissue minced by an arthroscopic shaver that was additionally augmented with autologous PRP. There was no difference between all 3 groups in terms of cell outgrowth or proliferation capacity. Metabolic activity relative to the cell number of chondrocytes isolated from shaver-minced cartilage was higher compared with chondrocytes isolated from cartilage that was derived by curettage or shaver-minced cartilage that was augmented with PRP. After chondrogenic stimulation, the normalized proteoglycan content was higher in spheroids of cells derived from shaver-minced cartilage augmented with PRP than in spheroids of cells derived from curettage. A high correlation of cell outgrowth, proliferation capacity, and viability between isolated cells from all 3 groups taken from an individual donor was observed. Chondrocytes isolated from human cartilage tissue that was harvested and minced with an arthroscopic shaver remained viable and proliferative. The augmentation of shaver-minced cartilage with PRP led to the enhanced proteoglycan production of chondrogenic spheroids in vitro, pointing toward the development of a cartilage-specific extracellular matrix. This in vitro study yields promising results regarding the use of an arthroscopic shaver and augmentation with PRP in the context of MCI. Knowledge that shaver mincing and augmentation with PRP are feasible for processing articular cartilage during MCI is highly relevant for surgical cartilage repair.


Assessment of false positives with the Humphrey Field Analyzer II perimeter with the SITA Algorithm.
To evaluate the effects of false-positive (FP) response errors on mean deviation (MD), pattern standard deviation (PSD), glaucoma hemifield test (GHT), and test duration in the Humphrey Field Analyzer's (HFA II) Swedish Interactive Threshold Algorithm (SITA; Carl Zeiss Meditec, Inc., Dublin, CA). Five individuals with glaucoma (ages 52, 63, 69, 77, and 78 years) and five individuals with normal, healthy eyes (ages 25, 34, 43, 45, and 52 years), participated in the study. Each subject was experienced in automated perimetry and performed multiple, monocular baseline SITA-standard (SITA-S) 24-2 visual field tests. In addition, normal subjects completed SITA-S 24-2 field examinations in which known frequencies of FP error were introduced (0%, 5%, 10%, 20%, or 33% frequency). Likewise, the subjects with glaucoma completed visual field examinations with 0%, 20%, and 33% error introduced during the test. Reported FP errors were significantly lower than the introduced frequency of error. The SITA algorithm more accurately identified FP errors when the MD and PSD diverged from normal. Test duration increased as introduced error frequencies increased. The Statpac single-field analyses indicated that two thirds of the tests with introduced errors produced a "low-patient-reliability" determination. HFA II SITA-S underestimates patients' FP errors, particularly among normal patients. High FP error frequencies can have adverse effects on MD and PSD, leading clinicians and researchers to an inaccurate determination of the amount and severity of visual field loss.


Hematological Evaluation of Three Common Teleosts in Relation to The Environmental Changes from Trang Province, Thailand.
Hematological evaluation of fish is essential to the assessment of their physiological status. This study describes the morphometric analysis and comparison of blood cell characteristics in Zanarchopterus sp., Gerres filamentosus Cuvier, 1829 and Leiognathus decorus (De Vis, 1884). The species were collected at two locations off the coast of Trang Province, Thailand. A comparative hematological evaluation was made to assess the effects of environmental conditions on the blood of the fish. Ten individuals of each species were collected from a seagrass bed at Libong Island, where human activities are increasing, and from a secluded sandy beach. Their blood samples were analysed using the blood smear technique. Erythrocytes of all the studied fishes were either elliptical or oval. The morphometric data from both locations showed that erythrocytes were of similar size, except for those of Zanarchopterus sp. Fish from both stations showed several types of leukocytes, including neutrophils and lymphocytes.The highest proportion of leukocytes was made up of lymphocytes, followed by neutrophils. However, monocytes were only observed in fish from Libong Island and the erythrocytic nuclei of fish collected from Libong Island were both reniform and lobate. Our results show the potential of hematological evaluation as an early warning signal of environmental impacts on aquatic animals. The determination of baseline parameters could provide a tool for the monitoring of environmental quality.


Concomitant development of oral dyskinesia and memory deficits in reserpine-treated male and female mice.
It has been suggested that reserpine-induced oral dyskinesia in rats may provide a new animal model of tardive dyskinesia. Both cognitive deficits and gender have been associated with the development of tardive dyskinesia. The aim of the present study was to investigate the effects of reserpine administration on the development of orofacial dyskinesia and on plus-maze discriminative avoidance task (DAT-an animal model of associative learning) in male and female mice. Male and female mice received 1.0 mg/kg reserpine or saline subcutaneously on day 1. On days 3, 6 and 8, the frequency of vacuous chewing movements (VCM) was quantified. On day 6, the DAT conditioning was performed, in a modified elevated plus-maze. In one of the enclosed arms, the animals received aversive stimulation (light and noise). On day 8, a test session was performed and the time spent by the animals in each of the enclosed arms was recorded. Our results showed that reserpine-treated male and female mice presented significantly higher VCM when compared with respective control groups in all observation days. On day 6, reserpine-treated female mice presented significantly higher VCM when compared with male mice injected with this drug. The DAT test performed on day 8 showed that the time spent in the aversive arm by saline-treated mice was significantly lower than the time spent in the non-aversive arm. This difference was not observed for reserpine-treated mice. Our results demonstrate the development of reserpine-induced oral dyskinesia in both male and female mice. While this oral dyskinesia is accompanied by a cognitive deficit in both genders, female mice tended to have more severe oral dyskinesia. It is suggested that reserpine-induced oral dyskinesia may provide a quick, simple and efficient mouse model of tardive dyskinesia.


Mucolytic agents and otitis media with effusion.
Middle ear effusion was obtained from children with otitis media with effusion and separated into thick (mucoid) and thin (serous) pools. Both effusion types contained similar amounts of non-dialysable solids. However, the thick effusions contained more mucus glycoprotein than the thin effusions, 25% and 8.2% respectively. Amino acid and carbohydrate analysis of the CsCl purified mucus glycoproteins demonstrated that the glycoprotein from the thick and thin effusions differed in their protein core, those from the thick effusions possessing a higher percentage of serine and threonine, the amino acids to which the sugar side-chains attach. They are also more glycosylated. N-acetyl cysteine and mercaptoethanol caused a fall in the viscosity of solutions of purified middle ear glycoprotein and effusion homogenate. However, longer term incubation caused a rise above the starting viscosity. This effect was concentration-dependent, and was mediated by low molecular weight components in the effusion and not the mucus glycoprotein. S-carboxymethyl cysteine had no effect on the viscosity of either the purified mucus glycoprotein or the effusion homogenate. Therefore, to produce a decrease in effusion viscosity in vivo, the concentration of mucolytic reaching the middle ear and the time it remains there are critical factors.


End-of-life care attitudes, values, and practices among health care workers.
This study aims to ascertain attitudes of health care workers on end-of-life care (EOLC) issues and to highlight the disparity that exists in countries with different backgrounds. It is a cross-sectional questionnaire survey across heterogeneous health care providers in India, Chile, the United Kingdom, and the Netherlands using an indigenously prepared questionnaire considering regional variations, covering different areas of EOLC. Of the 109 participants, 68 (62.4%) felt that cardiopulmonary resuscitation should be done selectively, 25 (22.9%) had come in contact with at least 1 patient who had asked them to hasten death, and 36 (33%) felt that training was insufficient to prepare them for skills in issues of EOLC. To avoid cumbersome through well-meant interventions, it is important that the caregiving team is aware of the patient's own wishes with respect to EOLC issues.


Improved method for generating exchange-correlation potentials from electronic wave functions.
Ryabinkin, Kohut, and Staroverov (RKS) [Phys. Rev. Lett. 115, 083001 (2015)] devised an iterative method for reducing many-electron wave functions to Kohn-Sham exchange-correlation potentials, vXC(𝐫). For a given type of wave function, the RKS method is exact (Kohn-Sham-compliant) in the basis-set limit; in a finite basis set, it produces an approximation to the corresponding basis-set-limit vXC(𝐫). The original RKS procedure works very well for large basis sets but sometimes fails for commonly used (small and medium) sets. We derive a modification of the method's working equation that makes the RKS procedure robust for all Gaussian basis sets and increases the accuracy of the resulting exchange-correlation potentials with respect to the basis-set limit.


Deterministic ratchets: route to diffusive transport.
The rectification efficiency of an underdamped ratchet operated in the adiabatic regime increases according to a scaling current-amplitude curve as the damping constant approaches a critical threshold; below threshold the rectified signal becomes extremely irregular and eventually its time average drops to zero. Periodic (locked) and diffusive (fully chaotic) trajectories coexist on fine tuning the amplitude of the input signal. The transition from regular to chaotic transport in noiseless ratchets has been studied numerically.


Mathematical derivation of optimal treatment schedules for the radiotherapy of human tumours. Fractionated irradiation of exponentially growing tumours.
A mathematical model is developed to allow derivation of optimal treatment schedules for the radiotherapy of exponentially-growing tumours. Preliminary calculations based on available data suggest that optimal schedules would (in general) be more protracted than conventional schedules and might achieve a significantly better tumour cell kill without causing excessive damage to normal connective tissue. The model is too simple, and the data inadequate, for the conclusions reached to be used as a guide to clinical practice at present. However, the analysis can be extended to more realistic models which may be of clinical benefit when the appropriate data can be obtained.


Afferent loop syndrome: diagnostic features with new imaging methods.
A patient had afferent loop obstruction with primary carcinoma of the gastric remnant and nonjaundiced biliary obstruction. We have presented the diagnostic features of ultrasonography, computed tomography, radionuclide studies, and fine-needle aspiration with injection of contrast material.


Virus-provoked rhinitis in patients who have allergies.
The most common illnesses in humans are the respiratory tract infections caused by viruses. When limited to the upper respiratory region, these infections often are designated as "a common cold." Viruses commonly associated with these upper respiratory infections (URI) include rhinoviruses (RVs), respiratory syncytial virus, influenza virus, parainfluenza virus, corona virus, and adenoviruses. Clinical observations have suggested that patients with allergic rhinitis and asthma experience more pronounced symptoms during a viral URI than patients who do not have allergies and who are infected with the same virus under similar circumstances. Using an experimental virus infection model in human volunteers with and without allergic rhinitis, several groups of clinical investigators have studied the effects of experimental RV infections. These observations indicate that the experimental virus infection may induce host responses that provoke enhanced immunoglobulin E (IgE) synthesis. Whether this translates into enhanced symptoms has been suggested in one study but not in another. This article will review these studies, which suggest that it is the host response to the virus and not the virus itself that plays the major role in symptom pathogenesis.


Clinical teaching: an evaluation of a problem orientated approach to psychiatric nurse education.
In a recent paper by one of the authors (Cormack 1080) the use of the problem orientated approach to nursing, and a proposed framework for assessing nursing needs, were discussed. Subsequently one of the writers (W.R.) utilized the problem orientated approach during the psychiatric nursing experience made available to student nurses undergoing the comprehensive modular training at the Highland College of Nursing and Midwifery, Scotland. This paper presents an evaluation of the problem orientated approach which has now been developing for 2 years. This paper describes the experience of W.R. in using a problem orientated approach to nursing diagnosis and nursing care prescriptions. It is argued that such an approach, combined with patient-centred rather than classroom based nurse education, is essential to enable psychiatric nurse teachers to teach effectively. Such a patient-centred approach is also necessary to clarify the psychiatric nurses' role and to shift the emphasis of psychiatric nurse education away from psychomotor skills to interpersonal skills. While it is recognized that this evaluation does not comply with the scientific criteria of a formal research based project, it is suggested that the experience of the authors and the comments of the many students involved in the exercise accurately reflect the problems encountered and the progress achieved.


Pharmacology of sertraline: a review.
Sertraline is a member of a new class of psychotherapeutic agents that selectively inhibit serotonin reuptake in the brain. Animal studies have demonstrated that inhibition of serotonin reuptake leads to enhanced serotonergic neurotransmission and indirectly results in a down-regulation of beta-adrenoceptors. The preclinical pharmacology of sertraline predicts antidepressant activity without accompanying anticholinergic, cardiotonic, or sedative side effects. Recent laboratory and clinical observations pertaining to body weight and obsessive compulsive disorder suggest the possibility of broader clinical indications for selective serotonin reuptake blockers such as sertraline.


Androgen receptor in cancer-associated fibroblasts influences stemness in cancer cells.
Androgen receptor (AR) regulation pathways are essential for supporting the growth and survival of prostate cancer cells. Recently, sub-populations of prostate cancer cells have been identified with stem cell features and are associated with the emergence of treatment-resistant prostate cancer. Here, we explored the function of AR in prostate cancer-associated fibroblasts (CAFs) relative to growth and stem cell-associated characteristics. CAFs were isolated from the murine cPten-/-L prostate cancer model and cultured with human prostate cancer epithelial (hPCa) cells. A murine-specific AR antisense oligonucleotide (ASO) was used to suppress the expression of AR in the CAF cells. CAFs express low, but significant levels of AR relative to fibroblasts derived from non-malignant tissue. CAFs promoted growth and colony formation of hPCa cells, which was attenuated by the suppression of AR expression. Surprisingly, AR-depleted CAFs promoted increased stem cell marker expression in hPCa cells. Interferon gamma (IFN-γ) and macrophage colony-stimulating factor (M-CSF) were increased in AR-depleted CAF cells and exhibited similar effects on stem cell marker expression as seen in the CAF co-culture systems. Clinically, elevated IFN-γ expression was found to correlate with histologic grade in primary prostate cancer samples. In summary, AR and androgen-dependent signaling are active in CAFs and exert significant effects on prostate cancer cells. IFN-γ and M-CSF are AR-regulated factors secreted by CAF cells, which promote the expression of stem cell markers in prostate cancer epithelial cells. Understanding how CAFs and other constituents of stromal tissue react to anti-cancer therapies may provide insight into the development and progression of prostate cancer.


Genetic analysis of HOXA11 gene in Chinese patients with cryptorchidism.
Cryptorchidism is the most common congenital anomaly in male children. Its aetiology remains unknown in the majority of cases. Because HOXA11 plays a vital role in regulating testicular descent, genetic variants in HOXA11 genes may contribute to the risk of cryptorchidism. In this study, mutation analysis was performed on the HOXA11 gene in a cohort of 89 patients with cryptorchidism. Furthermore, an association analysis of the HOXA11 tag single nucleotide polymorphism rs6461992 was performed in 168 patients with unilateral cryptorchidism and 193 controls. No pathogenic mutations were found. A significant difference in genotype and allele distribution was detected between cases and controls (p = .029 and .022 respectively). These results suggest that mutations in the coding sequence of HOXA11 might not be a common cause of cryptorchidism, while common polymorphisms in the HOXA11 gene might contribute to the risk of developing unilateral cryptorchidism.


Microglia-Specific Expression of Olfml3 Is Directly Regulated by Transforming Growth Factor β1-Induced Smad2 Signaling.
Microglia maturation takes place during the postnatal weeks and is characterized by the establishment of a unique microglia-specific gene expression pattern. Tmem119, Fcrls, Hexb, and Olfml3 have been identified among these microglia-specific genes. Transforming growth factor β1 (TGFβ1) has been reported as a critical factor for microglia maturation and maintenance and active TGFβ signaling precedes the inductions of microglial gene expression. In this study, we demonstrate Olfml3 expression in adult microglia and further provide evidence that TGFβ1 induces upregulation of Olfml3 expression in postnatal microglia. Using chromatin immunoprecipitation and microglia-specific silencing of TGFβ signaling in vitro and in vivo, we in clearly show that Olfml3 is a direct TGFβ1/Smad2 target gene. Together, our data underline the importance of TGFβ1 as a critical regulator of microglia functions and microglia maturation and further broaden our understanding of TGFβ1-mediated effects on the resident immune cells of the central nervous system.


Effects of arbuscular mycorrhizae on tomato yield, nutrient uptake, water relations, and soil carbon dynamics under deficit irrigation in field conditions.
Plant strategies to cope with future droughts may be enhanced by associations between roots and soil microorganisms, including arbuscular mycorrhizal (AM) fungi. But how AM fungi affect crop growth and yield, together with plant physiology and soil carbon (C) dynamics, under water stress in actual field conditions is not well understood. The well-characterized mycorrhizal tomato (Solanum lycopersicum L.) genotype 76R (referred to as MYC+) and the mutant nonmycorrhizal tomato genotype rmc were grown in an organic farm with a deficit irrigation regime and control regime that replaced evapotranspiration. AM increased marketable tomato yields by ~25% in both irrigation regimes but did not affect shoot biomass. In both irrigation regimes, MYC+ plants had higher plant nitrogen (N) and phosphorus (P) concentrations (e.g. 5 and 24% higher N and P concentrations in leaves at fruit set, respectively), 8% higher stomatal conductance (gs), 7% higher photosynthetic rates (Pn), and greater fruit set. Stem water potential and leaf relative water content were similar in both genotypes within each irrigation regime. Three-fold higher rates of root sap exudation in detopped MYC+ plants suggest greater capacity for water uptake through osmotic driven flow, especially in the deficit irrigation regime in which root sap exudation in rmc was nearly absent. Soil with MYC+ plants also had slightly higher soil extractable organic C and microbial biomass C at anthesis but no changes in soil CO2 emissions, although the latter were 23% lower under deficit irrigation. This study provides novel, field-based evidence for how indigenous AM fungi increase crop yield and crop water use efficiency during a season-long deficit irrigation and thus play an important role in coping with increasingly limited water availability in the future.


Fractures of the proximal segments of the pediatric distal radial metaphysis exhibit less angular stability than fractures of the distal segments.
The distal part of the forearm is divided into the physis, metaphysis, diaphyseal metaphyseal junction (DMJ) and diaphysis. The treatment of radial DMJ fractures is challenging because this region has diaphyseal characteristics. We speculated that the stability of metaphyseal fractures could vary depending on their proximity to the DMJ or physis. Our study aimed to investigate the stability of pediatric distal radius fractures in the physis, metaphysis and DMJ. Ninety-five patients were classified into three groups: group D, fracture line located within 1/2 of the width of the radius (WOR) from the physis; group M, fracture line located between 1/2 and 1 WOR from the physis; and group P, fracture line located between 1 and 2 WOR from the physis. We measured sagittal angulation and coronal angulation. A correction loss of less than 9° was defined as a 'stable reduction' outcome and one greater than 10° as a 'loss of reduction' outcome. The correction losses for sagittal angulation were significantly greater in groups M and P than in group D. The correction losses for coronal angulation were significantly greater in group P than in groups D and M. The incidence of 'loss of reduction' outcomes was significantly higher in groups M and P than in group D. The proximal segments of distal radial metaphyseal and DMJ fractures showed less angular stability than distal segments.


Some monoclonal antibody reagents (C219 and JSB-1) to P-glycoprotein contain antibodies to blood group A carbohydrate determinants: a problem of quality control for immunohistochemical analysis.
Monoclonal antibodies (MAb) C219 and JSB-1 have been used extensively in the analysis of P-glycoprotein expression in normal and malignant tissues. This study demonstrates that some commercial lots of these MAb, even those supplied as purified immunoglobulins, contain contaminating anti-A blood group antibodies. In both sources of reagent, the antibody was specific for a particular A structure, known as repetitive or Type 3 A. These observations may account for earlier studies showing polymorphic variation in P-glycoprotein expression in epithelial tissues and an apparent correlation with the A blood type of the donor. Such reactivity can be eliminated by absorption of anti-P-glycoprotein reagents with A erythrocytes. These data re-emphasize the importance of evaluating MAb samples for unsuspected contaminating antibodies.


Emerging roles for TFEB in the immune response and inflammation.
Inflammation is a central feature of an effective immune response, which functions to eliminate pathogens and other foreign material, and promote recovery; however, dysregulation of the inflammatory response is associated with a wide variety of disease states. The autophagy-lysosome pathway is one of 2 major degradative pathways used by the cell and serves to eliminate long-lived and dysfunctional proteins and organelles to maintain homeostasis. Mounting evidence implicates the autophagy-lysosome pathway as a key player in regulating the inflammatory response; hence many inflammatory diseases may fundamentally be diseases of autophagy-lysosome pathway dysfunction. The recent identification of TFEB and TFE3 as master regulators of macroautophagy/autophagy and lysosome function raises the possibility that these transcription factors may be of central importance in linking autophagy and lysosome dysfunction with inflammatory disorders. Here, we review the current state of knowledge linking TFEB and TFE3 to the processes of autophagy and inflammation and highlight several conditions, which are linked by these factors.


Preliminary results on the management of unruptured intracranial aneurysms with magnetic resonance angiography and computed tomographic angiography.
The goal was to assess the capability of magnetic resonance angiography (MRA) and computed tomographic angiography (CTA) to replace catheter angiography in the evaluation of unruptured intracranial aneurysms. A prospective evaluation of a 1-year period included all patients suspected of harboring unruptured intracranial aneurysms at a single institution. All patients underwent magnetic resonance imaging, MRA, and CTA, for comparison with intraoperative findings or results from catheter angiography. Both MRA and CTA now provide submillimeter resolution of vascular structures, with accurate detection of intracranial aneurysms of a diameter greater than or equal to 3 mm. This resolution calls into question the universal need for catheter angiography in the care of patients with suspected intracranial aneurysms. When the catheter angiography can be avoided, radiological costs can be reduced by as much as two-thirds while eliminating the risk of arterial injury and stroke. Excellent visualization of the intracranial vasculature was provided by both MRA and CTA. No vascular lesion was detected at surgery or by formal angiography that was not visualized by noninvasive angiographic techniques. The three-dimensional anatomy of the aneurysm complex (unavailable with catheter angiography) was well depicted by both MRA and CTA. CTA was unique in its capacity to display the relationship of vascular structures to bone, information that is invaluable for planning operative strategies for lesions such as carotidophthalmic artery aneurysms. Additionally, acquisition of CTA images was very rapid, with a scanning time of less than 1 minute. Both MRA and CTA allowed for retrospective manipulation of data into an infinite number of views, including views that paralleled those encountered through the operative microscope. Additionally, both MRA and CTA can depict the internal anatomy of aneurysms, an ability not possessed by intra-arterial angiography. This ability alerts the surgeon to possible intraoperative risks, such as plaque in the lumen of an aneurysm or calcium within the walls of the arteries. Both MRA and CTA provide several advantages over digital subtraction angiography, in addition to reduced costs and avoidance of arterial injury and stroke. These include retrospective manipulation of data in a 360-degree format, visualization of the internal anatomy of arteries and aneurysms, three-dimensional depiction of anatomy, and rapid data acquisition. Preliminary data and a review of the literature suggest that MRA, when used in concert with CTA, can replace catheter angiography in the assessment of select patients harboring unruptured intracranial aneurysms. Although no firm conclusions or generalizations can be drawn from this small cohort of patients, it is hoped that this report will stimulate interest and further study at other institutions.


Tardive dyskinesia rating scales.
The authors review the history of the introduction of the concept of tardive dyskinesia (TD). They discuss the various ranges of prevalence of TD and also of senile dyskinesias and point out that these are two different entities. They critically discuss the use of various rating scales for measuring TD and then review the literature on the use of various other tools used for measuring TD. The issue of practical difficulties and flaws encountered in the assessment of TD is also addressed. Lastly, they suggest that various electromyographic or other gadgetry may very well identify neuromuscular abnormalities at an earlier point in time and this could lead to earlier detection and intervention as well as further the information about pathophysiology of this disorder.


Familial Kleine-Levin Syndrome: A Specific Entity?
Kleine-Levin syndrome (KLS) is a rare, mostly sporadic disorder, characterized by intermittent episodes of hypersomnia plus cognitive and behavior disorders. Although its cause is unknown, multiplex families have been described. We contrasted the clinical and biological features of familial versus sporadic KLS. Two samples of patients with KLS from the United States and France (n = 260) were studied using clinical interviews and human leukocyte antigen (HLA) genotyping. A multiplex family contained two or more first- or second-degree affected relatives (familial cases). Twenty-one patients from 10 multiplex families (siblings: n = 12, including two pairs of monozygotic twins; parent-child: n = 4; cousins: n = 2; uncle-nephews: n = 3) and 239 patients with sporadic KLS were identified, yielding to 4% multiplex families and 8% familial cases. The simplex and multiplex families did not differ for autoimmune, neurological, and psychiatric disorders. Age, sex ratio, ethnicity, HLA typing, karyotyping, disease course, frequency, and duration of KLS episodes did not differ between groups. Episodes were less frequent in familial versus sporadic KLS (2.3 ± 1.8/y versus 3.8 ± 3.7/y, P = 0.004). Menses triggered more frequently KLS onset in the nine girls with familial KLS (relative risk, RR = 4.12, P = 0.03), but not subsequent episodes. Familial cases had less disinhibited speech (RR = 3.44, P = 0.049), less combined hypophagia/hyperphagia (RR = 4.38, P = 0.006), more abrupt termination of episodes (RR = 1.45, P = 0.04) and less postepisode insomnia (RR = 2.16, P = 0.008). There was similar HLA DQB1 distribution in familial versus sporadic cases and no abnormal karyotypes. Familial KLS is mostly present in the same generation, and is clinically similar to but slightly less severe than sporadic KLS.


Mutant TNFalpha negatively regulates human breast cancer stem cells from MCF7 in vitro.
Understanding the biology of breast cancer stem cells and trying new ways to obliterate these cells would be a key step in developing cures for breast cancer. The objective of this study was to investigate the effect of mutant TNFalpha on human breast cancer stem cells derived from MCF7 cell line under the characterization of biologic features of these cells in vitro. By FACS analysis and sorting, we got MCF7 side population (SP) cells and showed that MCF7 SP cells possess cancer stem cell characteristics using the accepted breast cancer stem cell markers, but do not express multiple drug resistance transporters. Furthermore, by RT-PCR, these stem cells were found to constitutively express TNFR-p55 and TNFR-p75. After being treated with Mt rh471 TNFalpha, SP cells displayed a decreased self-renewal ability and an increased apoptosis by three different methods. When monocolony antibody against TNFR-p55 was added into the culture medium, the inhibitory effect of Mt rh471 TNFalpha on self-renewal was blocked completely, but this was not the case for that of Wt rhTNFalpha. The possible reasons might be that the increased binding of Mt rh471 TNFalpha mainly to TNFR-p55 results in induction of apoptosis of SP cells, while Wt rhTNFalpha could bind to both TNFR-p55 and TNFR-p75 which would lead to NFkappaB activity, resulting in a discounted apoptotic effect. These data suggest that Mt rh471 TNFalpha might be a negative regulator of the breast cancer stem cell-like cells and have the potential to treat breast cancer in clinic.


Seven Clues to Ligand Noninnocence: The Metallocorrole Paradigm.
Noninnocent ligands do not allow an unambiguous definition of the oxidation state of a coordinated atom. When coordinated, the ligands also cannot be adequately represented by a classic Lewis structure. A noninnocent system thus harbors oxidizing (holes) or reducing equivalents (electrons) that are delocalized over both the ligand and the coordinated atom. To a certain degree, that is true of all complexes, but the phenomenon is arguably most conspicuous in complexes involving ligands with extended π-systems. The electronic structures of such systems have often been mischaracterized, thereby muddying the chemical literature to the detriment of students and newcomers to the field. In recent years, we have investigated the electronic structures of several metallocorrole families, several of which have turned out to be noninnocent. Our goal here, however, is not to present a systematic account of the different classes of metallocorroles, but rather to focus on seven major tools (in a nod to A. G. Cairns-Smith's Seven Clues to the Origin of Life) that led us to recognize noninnocent behavior and subsequently to characterize the phenomenon in depth. (1) The optical probe: For a series of noninnocent meso-triarylcorrole derivatives with different para substituents X, the Soret maxima are typically exquisitely sensitive to the nature of X, red-shifting with increasing electron-donating character of the group. No such substituent sensitivity is observed for the Soret maxima of innocent triarylcorrole derivatives. (2) Quantum chemistry: Spin-unrestricted density functional theory calculations permit a simple and quick visualization of ligand noninnocence in terms of the spin density profile. Even for an S = 0 complex, the broken-symmetry method often affords a spin density profile that, its fictitious character notwithstanding, helps visualize the intramolecular spin couplings. (3) NMR and EPR spectroscopy: In principle, these two techniques afford experimental probes of the electronic spin density. (4) Structure/X-ray crystallography. Ligand noninnocence in metallocorroles is often reflected in small but distinct skeletal bond length alternations in and around the bipyrrole part of the macrocycle. In addition, for Cu and some Ag corroles, ligand noninnocence manifests itself via a strong saddling of the macrocycle. (5) Vibrational spectroscopy. Unsurprisingly, the aforementioned bond length alternations translate to structure-sensitive vibrational marker bands. (6) Electrochemistry. Noninnocent metallocorroles exhibit characteristically high reduction potentials, but caution should be exercised in turning the logic around. A high reduction potential does not necessarily signify a noninnocent metallocorrole; certain high-valent metal centers also undergo metal-centered reduction at quite high potentials. (7) X-ray absorption spectroscopy (XAS). By focusing on a given element, typically the central atom in a coordination complex, X-ray absorption near-edge spectroscopy (XANES) can provide uniquely detailed local information on oxidation and spin states, ligand field strength, and degree of centrosymmetry. For metallocorroles, some of the most clear-cut distinctions between innocent and noninnocent systems have come from the K-edge XANES of Mn and Fe corroles. For researchers faced with a new, potentially noninnocent system, the take-home message is to employ a good majority (i.e., at least four) of the above methods to arrive at a reliable conclusion vis-à-vis noninnocence.


[Prognostic factors of vaginal cancer].
Vaginal cancer is a rare disease entity in the gynecologic oncology field. Prognostic factors of the disease, however, are not established to date. Possible prognostic factors such as tumor location in vagina, tumor size, age,staging and histopathological grading are discussed following a literature review. Because the case number of the report from a single institute is really limited, accumulation and analysis of the case of multi-institutional registration are mandatory.


Validations and psychological properties of a simplified Chinese version of pain anxiety symptoms scale (SC-PASS).
The Pain Anxiety Symptoms Scale (PASS) has been developed to evaluate pain anxiety, which leads to avoidance of daily activities and normal movements. However, a simplified Chinese version of PASS is still not available. Physicians are not aware of which patients are prone to anxiety, and what the risk factors are.To cross-culturally adapt the PASS into a simplified Chinese version and test the reliability and validity. Factors affecting pain anxiety were also explored.The PASS was first translated into a simplified Chinese version according to a forward-backward method. Then, validations were tested including content validity, construct validity, and reliability. Content validity was analyzed by response trend. Construct validity was analyzed by confirmatory factor analysis (CFA), exploratory factor analysis, and priori hypotheses testing. Reliability was analyzed by internal consistency and test-retest reliability. Risk factors of catastrophizing were analyzed by performing multivariate liner regression.A total of 219 patients were included in the study. The scores of items were well distributed. Both CFA and exploratory factor analysis suggested a 2nd-order, 4-factor model, accounting for 65.42% of the total variance according to principle component analysis. SC-PASS obtained good reliability with a Cronbach α = 0.92 and ICC = 0.90. College education, long pain duration, and both married and divorced status were risk factors. Factors reduced pain-related anxiety were no medication assumption, female sex, widowed status, non-Han ethnicity, and having no religious belief.The SC-PASS was applicable in Chinese patients and it was suitable for the clinical uses in mainland China.


[Sequence analysis of VP1 gene of the duck hepatitis A virus type 3 strains isolated from Shandong Province of China in 2012].
To reveal the genetic variation of the viral protein 1 (VP1) gene of the duck hepatitis A virus type 3 (DHAV-3), the VP1 gene of 13 virulent DHAV-3 strains isolated from Shandong province of China in 2012 were amplified by RT-PCR, sequenced and analyzed. The results showed that all the VP1 genes of the 13 isolates contained 720 nucleotides encoding 240 amino acids, and shared with nucleotide identities of 94. 6%-99.9% and amino acid identities of 95.0%-100%. The nucleotide and amino acid sequence homologies between the 13 DHAV-3 isolates and other 31 DHAV-3 reference strains were 92.5%-100% and 90. 8%-100%, respectively. Phylogenetic analysis showed that the VP1 gene of DHAV-3 had distinct geographical characteristics. Distribution of genotypes of the 44 DHAV-3 strains was as follows: except the vaccine strain B63, all the other Chinese isolates belonged to genotype I (GI), Vietnamese wild isolates mainly belonged to subtype 1 (S1) of genotype II (GII), and all Korean isolates belonged to subtype 2 (S2) of GII.


Additive or synergetic effects of phenolic compounds on human low density lipoprotein oxidation.
The in vitro assessment of the antioxidant capacity of four phenolic compounds; catechin, hesperidin, ferulic acid, and quercetin was evaluated by the examination of their ability to inhibit copper (Cu(2+))-mediated human low density lipoprotein (LDL) oxidation by using the thiobarbituric acid-reactive substances (TBARS) assay. Individually, the enrichment of LDLs with various concentrations of catechin, hesperidin, ferulic acid, and quercetin produced both antioxidant and prooxidant effects depending on enrichment concentrations of the polyphenolic compounds. Catechin and hesperidin had predominantly antioxidant effects (51.1%, 76.9%, respectively) while ferulic acid and quercetin had mostly prooxidant effects (166.4%; 191.8%, respectively) on LDL oxidation. However, when the mixture of the four phenolic compounds was used to enrich the LDLs, significant antioxidant capacity was demonstrated at all enrichment levels with a dose-response. Synergistic effects of the polyphenolic compounds as mixtures in preventing human LDL oxidation may reflect that nutritional advantages are found in the consumption of a variety of fruits and vegetables in preventing LDL oxidation and perhaps a host of cardiovascular diseases.


[Design and implementation of a molecular method for influenza A virus (H1N1) in Cuba].
From March through April of 2009, Mexico notified outbreaks of respiratory illness, due to a new influenza virus of swine origin, which spread over rapidly via human-to-human transmission. The molecular methods currently in use were not suitable because the genome composition based on gene segments of swine, avian and human origin was quite different from the influenza A virus (H1N1) circulating at that time. Based on the published sequences, a set of specific primers for the HA gene was designed to evaluate a new RT-PCR assay. The RT-PCR assay processed 3 197 clinical samples from suspected cases of pandemic influenza A (H1N1) infection. The novel optimized method obtained a 262 pb segment, without unspecific reactions. The new method proved to be useful in the diagnosis and subtyping of pandemic HINI influenza virus. The amplified product was verified by nucleotide sequencing, thus confirming the virus. The introduction of this new assay for the laboratory surveillance of influenza virus strengthens the diagnostic capacity of the National Reference Laboratory.


Inflammatory dentigerous cyst of mandibular first premolar associated with endodontically treated primary first molar: a rare case report.
Inflammatory dentigerous cysts usually occur in the mixed dentition. It has been reported that inflammatory lesions from the root area of a deciduous tooth bring about the development of dentigerous cysts around the unerupted permanent tooth bud. Endodontic treatment is a common and successful procedure for periapical inflammation in children. An inflammatory dentigerous cyst can occur in conjunction with endodontically treated primary tooth. This article reports a case of 6 years and 6 months old boy, with a single, well-defined, unilocular, radiolucent area enclosing the first right unerupted mandibular premolar, accidentally discovered on the panoramic radiograph. The first right primary molar had received a root canal treatment 18 months prior. Clinical findings combined with radiographic and microscopic examinations confirmed the diagnosis of inflammatory dentigerous cyst. As treatment, enucleation of the cyst with removal of the involved permanent tooth was chosen and a removable partial denture was supplied to the patient after surgery. The 5-year follow-up revealed good healing of the bony lesion and displaced teeth. This case presented a severe and rare complication of endodontically treated primary tooth, and the recommendation includes: (1) early diagnosis of dentigerous cysts, which is essential to prevent extensive treatment; (2) more information on the adverse side effects of an endodontic treatment should be given to patients and parents; (3) patients should be informed about the importance of follow-ups and radiographic follow-up should be routinised.


Prognostic factors for surgically resected squamous cell carcinoma of the lower oral cavity.
The objective of this study was to evaluate the impact of clinical variables on survival rates in patients with squamous cell carcinomas in the lower oral cavity. We conducted a retrospective study of patients who exhibited a histological diagnosis of squamous cell carcinoma of the lower oral cavity, who underwent surgery. Data on clinical, histological, and treatment variables were collected to assess the effect of these variables on global survival and disease-free curves. We studied 117 patients, 86 (73.5%) males and 31 (26.5%) females, who underwent surgery between January 2005 and June 2009. The overall survival rate was 74.4% after two years, and the disease-free rate was 67.5%. Midline invasion by the primary tumor negatively impacted overall survival (P=0.02) and disease-free survival (P=0.01). The disease-free survival rate of patients with histologically confirmed neck metastases was 76.8% versus 59% for patients without metastases (P=0.01). Disease-free survival of patients with one affected lymph node was 89.5%, and 45.2% for more than one affected lymph node (P<0.01). Patients who ended radiotherapy in less than 60 days exhibited a disease-free rate of 59.0%, and patients whose treatment lasted more than 60 days exhibited a rate of 77.1% (P=0.06). In our study, primary tumor invasion of the midline, the presence of more than one affected lymph node as confirmed by histology, the delaying radiotherapy for more than 56 days and radiotherapy that lasted longer than 60 days worsen patient prognosis.


Functional annotation of putative regulatory elements at cancer susceptibility Loci.
Most cancer-associated genetic variants identified from genome-wide association studies (GWAS) do not obviously change protein structure, leading to the hypothesis that the associations are attributable to regulatory polymorphisms. Translating genetic associations into mechanistic insights can be facilitated by knowledge of the causal regulatory variant (or variants) responsible for the statistical signal. Experimental validation of candidate functional variants is onerous, making bioinformatic approaches necessary to prioritize candidates for laboratory analysis. Thus, a systematic approach for recognizing functional (and, therefore, likely causal) variants in noncoding regions is an important step toward interpreting cancer risk loci. This review provides a detailed introduction to current regulatory variant annotations, followed by an overview of how to leverage these resources to prioritize candidate functional polymorphisms in regulatory regions.


Dietary intervention in the management of phenylketonuria: current perspectives.
Phenylketonuria (PKU) is a well-described inborn error of amino acid metabolism that has been treated for >60 years. Enzyme deficiency causes accumulation of phenylalanine (Phe) and if left untreated will lead to profound and irreversible intellectual disability in most children. Traditionally, it has been managed with a low-Phe diet supplemented with a Phe-free protein substitute although newer treatment options mainly in combination with diet are available for some subgroups of patients with PKU, for example, sapropterin, large neutral amino acids, and glycomacropeptide. The diet consists of three parts: 1) severe restriction of dietary Phe; 2) replacement of non-Phe l-amino acids with a protein substitute commonly supplemented with essential fatty acids and other micronutrients; and 3) low-protein foods from fruits, some vegetables, sugars, fats and oil, and special low-protein foods (SLPF). The prescription of diet is challenging for health professionals. The high-carbohydrate diet supplied by a limited range of foods may program food preferences and contribute to obesity in later life. Abnormal tasting and satiety-promoting protein substitutes are administered to coincide with peak appetite times to ensure their consumption, but this practice may impede appetite for other important foods. Intermittent dosing of micronutrients when combined with l-amino acid supplements may lead to their poor bioavailability. Much work is required on the ideal nutritional profiling for special SLPF and Phe-free l-amino acid supplements. Although non-diet treatments are being studied, it is important to continue to fully understand all the consequences of diet therapy as it is likely to remain the foundation of therapy for many years.


Sodium Butyrate Protects N2a Cells against Aβ Toxicity In Vitro.
Alzheimer's disease (AD) is a common neurodegenerative disease. Aβ plays an important role in the pathogenesis of AD. Sodium butyrate (NaB) is a short-chain fatty acid salt that exerts neuroprotective effects such as anti-inflammatory, antioxidant, antiapoptotic, and cognitive improvement in central nervous system diseases. The aim of this study is to research the protective effects of NaB on neurons against Aβ toxicity and to uncover the underlying mechanisms. The results showed that 2 mM NaB had a significant improvement effect on Aβ-induced N2a cell injury, by increasing cell viability and reducing ROS to reduce injury. In addition, by acting on the GPR109A receptor, NaB regulates the expression of AD-related genes such as APP, NEP, and BDNF. Therefore, NaB protects N2a cells from Aβ-induced cell damage through activating GPR109A, which provides an innovative idea for the treatment of AD.


Transfusion transmitted hepatitis: where do we stand now? A one center study in upper egypt.
Despite progress made in the prevention of transfusion-transmitted infections (TTI) over the last few years, they continue to be a problem in many parts of the world, particularly in multitransfused patients. The aim of this study was to estimate the prevalence of hepatitis B virus (HBV), hepatitis C virus (HCV), and to evaluate the screening and vaccination program among our cohort of multitransfused children from Qena, Upper Egypt. One-hundred children suffering from diseases requiring repeated blood transfusions were included in the study. They were classified into group 1, which included 67 children with thalassemia, and group 2, which included 33 children with hemophilia. Screening for hepatitis B surface antigen, hepatitis B surface antibody, hepatitis B core antibody and antibody to HCV was done using a second-generation enzyme-linked immunosorbent assay technique. Only 12% of all patients were either acutely or chronically infected with HBV. 46% were immune due to previous vaccination, whereas 39% of patients were not protected from HBV infection. HCV antibodies were positive in 45% of cases. Seventy-eight patients had a complete hepatitis B vaccination in the form of three doses as documented by birth certificate. Thirty-six patients mentioned history suggestive of hepatitis. The prevalence of the studied hepatitis markers was similar in both the thalassemia and hemophilia groups of children. Transfusion-transmitted hepatitis is still a major problem for multitransfused children in Egypt. More effort is required to reduce the infection rate through proper screening of blood and blood products, strict emphasis on receiving the vaccine, regular follow-up for those children with a hepatitis B antibody titer, and providing booster doses for those in need.


Peptidoglycan cross-linking in glycopeptide-resistant Actinomycetales.
Synthesis of peptidoglycan precursors ending in D-lactate (D-Lac) is thought to be responsible for glycopeptide resistance in members of the order Actinomycetales that produce these drugs and in related soil bacteria. More recently, the peptidoglycan of several members of the order Actinomycetales was shown to be cross-linked by L,D-transpeptidases that use tetrapeptide acyl donors devoid of the target of glycopeptides. To evaluate the contribution of these resistance mechanisms, we have determined the peptidoglycan structure of Streptomyces coelicolor A(3)2, which harbors a vanHAX gene cluster for the production of precursors ending in D-Lac, and Nonomuraea sp. strain ATCC 39727, which is devoid of vanHAX and produces the glycopeptide A40296. Vancomycin retained residual activity against S. coelicolor A(3)2 despite efficient incorporation of D-Lac into cytoplasmic precursors. This was due to a D,D-transpeptidase-catalyzed reaction that generated a stem pentapeptide recognized by glycopeptides by the exchange of D-Lac for D-Ala and Gly. The contribution of L,D-transpeptidases to resistance was limited by the supply of tetrapeptide acyl donors, which are essential for the formation of peptidoglycan cross-links by these enzymes. In the absence of a cytoplasmic metallo-D,D-carboxypeptidase, the tetrapeptide substrate was generated by hydrolysis of the C-terminal D-Lac residue of the stem pentadepsipeptide in the periplasm in competition with the exchange reaction catalyzed by D,D-transpeptidases. In Nonomuraea sp. strain ATCC 39727, the contribution of L,D-transpeptidases to glycopeptide resistance was limited by the incomplete conversion of pentapeptides into tetrapeptides despite the production of a cytoplasmic metallo-D,D-carboxypeptidase. Since the level of drug production exceeds the level of resistance, we propose that L,D-transpeptidases merely act as a tolerance mechanism in this bacterium.


The Utility of Invengenx® Bovine Patch for Right Ventricular Outflow Tract (RVOT) Reconstruction and Augmentation in the Surgical Management of Tetralogy of Fallot (TOF): A Contemporary Study and Review of the Literature.
Background and objective Complex congenital heart diseases (CHDs), such as the tetralogy of Fallot (TOF), often warrant reconstruction and augmentation of the right ventricular outflow tract (RVOT). This procedure requires the use of both synthetic and natural materials. However, finding the ideal material for tissue implants can be challenging. Biological materials often face issues such as tissue degeneration, calcium deposition, antigenicity, rejection, shrinkage, and fibrosis. These issues can lead to complications such as stenosis and insufficiency, potentially requiring early reoperations. In light of this, this study aimed to investigate the effectiveness of the Invengenx® bovine patch for RVOT reconstruction and augmentation. Methods This was a retrospective observational study conducted among eight children who underwent TOF correction cardiac surgery. Their demographic and clinical characteristics, intraoperative findings, and postoperative follow-up results at six months were collected from the hospital patient database. Results There were no deaths or complications in this study. We observed a significant reduction in the gradient across the pulmonary valve and the outflow tract at six months post-procedure. The analysis demonstrated that the Invengenx® bovine patch was successful and did not lead to any complications. Conclusions This study demonstrates the safety and efficacy of this engineered bovine pericardial patch (Invengenx®) as a cardiovascular substitute for surgical repair of both simple and more complex congenital cardiac defects.


Generation and control of localized terahertz fields in photoemitted electron plasmas.
Dense micron-sized electron plasmas, such as those generated upon irradiation of nanostructured metallic surfaces by intense femtosecond laser pulses, constitute a rich playground to study light-matter interactions, many-body phenomena, and out-of-equilibrium charge dynamics. Besides their fundamental interest, laser-induced plasmas hold great potential for the generation of localized terahertz radiation pulses. However, the underlying mechanisms ruling the formation and evolution of such plasmas are not yet well understood. Here, we develop a comprehensive microscopic theory to predictably describe the spatiotemporal dynamics of laser-pulse-induced plasmas. Through detailed analysis of electron emission, metal screening, and plasma cloud interactions, we investigate the spatial, temporal, and spectral characteristics of the so-generated terahertz fields, which can be extensively controlled through the metal morphology and the illumination conditions. We further describe the interaction with femtosecond electron beams to explain recent ultrafast electron microscopy experiments, whereby the position and temporal dependence of the observed electron acceleration permits assessing the associated terahertz field. Besides its potential application to the design of low-frequency light sources, our work contributes fundamental insight into the generation and dynamics of micron-scale electron plasmas and their interaction with ultrafast electron pulses.


Solitary versus shock wave acceleration in laser-plasma interactions.
The excitation of nonlinear electrostatic waves, such as shock and solitons, by ultraintense laser interaction with overdense plasmas and related ion acceleration are investigated by numerical simulations. Stability of solitons and formation of shock waves is strongly dependent on the velocity distribution of ions. Monoenergetic components in ion spectra are produced by "pulsed" reflection from solitary waves. Possible relevance to recent experiments on "shock acceleration" is discussed.


MicroRNA-377 suppresses initiation and progression of esophageal cancer by inhibiting CD133 and VEGF.
Esophageal cancer is one of the most lethal cancers worldwide with poor survival and limited therapeutic options. The discovery of microRNAs created a new milestone in cancer research. miR-377 is located in chromosome region 14q32, which is frequently deleted in esophageal squamous cell carcinoma (ESCC), but the biological functions, clinical significance and therapeutic implication of miR-377 in ESCC are largely unknown. In this study, we found that miR-377 expression was significantly downregulated in tumor tissue and serum of patients with ESCC. Both tumor tissue and serum miR-377 expression levels were positively correlated with patient survival. Higher serum miR-377 expression was inversely associated with pathologic tumor stage, distant metastasis, residual tumor status and chemoradiotherapy resistance. The roles of miR-377 in suppressing tumor initiation and progression, and the underlying molecular mechanisms were investigated. Results of in vitro and in vivo experiments showed that miR-377 overexpression inhibited the initiation, growth and angiogenesis of ESCC tumors as well as metastatic colonization of ESCC cells, whereas silencing of miR-377 had opposite effects. Mechanistically, miR-377 regulated CD133 and VEGF by directly binding to their 3' untranslated region. Moreover, systemic delivery of formulated miR-377 mimic not only suppressed tumor growth in nude mice but also blocked tumor angiogenesis and metastasis of ESCC cells to the lungs without overt toxicity to mice. Collectively, our study established that miR-377 plays a functional and significant role in suppressing tumor initiation and progression, and may represent a promising non-invasive diagnostic and prognostic biomarker and therapeutic strategy for patients with ESCC.


Cultural adaptation and specifics of the Fit & Strong! program in Portugal.
Fit & Strong! is a physical activity/behavior change evidence-based intervention for persons with osteoarthritis (OA) that was developed and tested in USA. This article describes the development of a new culturally adapted Portuguese version of Fit & Strong!, reviews the methods used, and describes the new features of the Portuguese program. Six steps were implemented for the cultural adaptation: training the Portuguese research team, materials translation, needs assessment which includes literature review, focus group with older adults with lower extremity joint pain, interviews with experts about Fit & Strong! format and content, program instructor training, and pilot study and program implementation. At the conclusion of the pilot, debriefing interviews were held with participants and instructors to obtain their opinions about the program. Thematic content analysis and SWOT analysis were used to analyze the qualitative data. Findings indicated needed changes to the original Fit & Strong! program protocol. In the Manuals, language was simplified and more pictures added to be suitable for people with lower level of literacy. Also, practical examples described in Manuals were adjusted or substituted to better fit the Portuguese culture. As a description of Portuguese organizations in the field, Thermal Spa and Mediterranean diet were added to the Manual. We recommend using two instructors to address individual challenges during the sessions. The Portuguese version of Fit & Strong! introduces all the necessary changes to become a relevant new intervention program to raise quality of life of patients with OA in Portugal.


Canadian Cardiovascular Society 2009 Consensus Conference on the management of adults with congenital heart disease: shunt lesions.
With advances in pediatric cardiology and cardiac surgery, the population of adults with congenital heart disease (CHD) has increased. In the current era, there are more adults with CHD than children. This population has many unique issues and needs. Since the 2001 Canadian Cardiovascular Society Consensus Conference report on the management of adults with congenital heart disease, there have been significant advances in the field of adult CHD. Therefore, new clinical guidelines have been written by Canadian adult CHD physicians in collaboration with an international panel of experts in the field. Part I of the guidelines includes recommendations for the care of patients with atrial septal defects, ventricular septal defects, atrioventricular septal defects and patent ductus arteriosus. Topics addressed include genetics, clinical outcomes, recommended diagnostic workup, surgical and interventional options, treatment of arrhythmias, assessment of pregnancy risk, and follow-up requirements. The complete document consists of four manuscripts, which are published online in the present issue of The Canadian Journal of Cardiology. The complete document and references can also be found at www.ccs.ca or www.cachnet.org.


Efficient all-optical modulator based on a periodic dielectric atomic lattice.
All-optical devices used to process optical signals without electro-optical conversion plays a vital role in the next generation of optical information processing systems. We demonstrate an efficient all-optical modulator that utilizes a periodic dielectric atomic lattice produced in a gas of 85Rb vapor. Four orders of diffraction patterns are observed when a probe laser is passed through the lattice. The frequency shift of the peak of each diffraction order can be tuned by adjusting the control laser power and two-photon detuning, enabling this device to be used as a multi-channel all-optical modulator. Both theoretical simulations and experimental results demonstrate that this modulator can operate over a frequency band extending from about 0 to 60 MHz. This work may pave the way for studying quantum information processing and quantum networking proposed in atomic ensembles.


Herd immunity: challenges and the way forward in Korea.
Vaccination is considered to be the most effective measure for preventing the spread of coronavirus disease 2019 (COVID-19). Many countries, including of Korea, are focusing on achieving herd immunity with the goal of reaching a vaccination rate of 70-80%. However, achieving herd immunity does not mean eradicating COVID-19, and the following challenges can occur in the process of achieving herd immunity. First, as the vaccination rate is likely to slow down over time, it is necessary to promote the benefits of vaccination through risk communication strategies and provide incentives for those who have been vaccinated. Second, a booster dose may be required depending on future studies on vaccine-induced immunity. Third, since variants capable of evading immunity and with higher transmissibility can emerge, rapid contract tracing and regular community genomic surveillance could help mitigate the impact of new variants. When the impact of COVID-19 is controlled to the level of seasonal influenza, the current public health measures that have been strictly imposed on society since the beginning of the pandemic will no longer be needed. The overall response strategy to COVID-19 will need to change accordingly, based on evaluations of the level of population immunity. These changes will include more efficient and targeted contact tracing and eased quarantine measures for vaccinated close contacts and travelers. Mask wearing and a minimum of social distancing will still be required in the journey towards the end of the pandemic. The COVID-19 pandemic will end, but the virus will not disappear.


Transcriptome Metabolic Characterization of Tuber borchii SP1-A New Spanish Strain for In Vitro Studies of the Bianchetto Truffle.
Truffles are ascomycete hypogeous fungi belonging to the Tuberaceae family of the Pezizales order that grow in ectomycorrhizal symbiosis with tree roots, and they are known for their peculiar aromas and flavors. The axenic culture of truffle mycelium is problematic because it is not possible in many cases, and the growth rate is meager when it is possible. This limitation has prompted searching and characterizing new strains that can be handled in laboratory conditions for basic and applied studies. In this work, a new strain of Tuber borchii (strain SP1) was isolated and cultured, and its transcriptome was analyzed under different in vitro culture conditions. The results showed that the highest growth of T. borchii SP1 was obtained using maltose-enriched cultures made with soft-agar and in static submerged cultures made at 22 °C. We analyzed the transcriptome of this strain cultured in different media to establish a framework for future comparative studies, paying particular attention to the central metabolic pathways, principal secondary metabolite gene clusters, and the genes involved in producing volatile aromatic compounds (VOCs). The results showed a transcription signal for around 80% of the annotated genes. In contrast, most of the transcription effort was concentrated on a limited number of genes (20% of genes account for 80% of the transcription), and the transcription profile of the central metabolism genes was similar in the different conditions analyzed. The gene expression profile suggests that T. borchii uses fermentative rather than respiratory metabolism in these cultures, even in aerobic conditions. Finally, there was a reduced expression of genes belonging to secondary metabolite clusters, whereas there was a significative transcription of those involved in producing volatile aromatic compounds.


Increased incidence of empyema in Polynesian children.
The aim of this study was to review the epidemiology, treatment and outcome of surgically managed empyema in children. A retrospective review was undertaken of all surgically managed empyema at Starship Children's Hospital (Auckland, New Zealand) from 1 July 2003 to 30 June 2008. Of the 93 children diagnosed with empyema, 62 were managed surgically (55 VATS, 7 thoracotomy) and 31 with tube thoracostomy alone. 71% were of Maori or Pacific ethnicity despite making up just 30% of the New Zealand paediatric population (p<0.0001). Median duration of chest drainage following VATS was 3 days and postoperative hospital stay 14 days. There was a 5% conversion of VATS to thoracotomy. The VATS complication rate was 16%: one intraoperative cardiorespiratory arrest following rupture of an intrapulmonary abscess into the bronchial tree, two contralateral empyema, one recurrent empyema, four air leaks and a wound infection. For the first time increased incidence of empyema in the Polynesian population has been documented. Severity of empyema may be higher within the Polynesian population affecting treatment outcome.


Heme-thiolate sulfenylation of human cytochrome P450 4A11 functions as a redox switch for catalytic inhibition.
Cytochrome P450 (P450, CYP) 4A11 is a human fatty acid ω-hydroxylase that catalyzes the oxidation of arachidonic acid to the eicosanoid 20-hydroxyeicosatetraenoic acid (20-HETE), which plays important roles in regulating blood pressure regulation. Variants of P450 4A11 have been associated with high blood pressure and resistance to anti-hypertensive drugs, and 20-HETE has both pro- and antihypertensive properties relating to increased vasoconstriction and natriuresis, respectively. These physiological activities are likely influenced by the redox environment, but the mechanisms are unclear. Here, we found that reducing agents (e.g. dithiothreitol and tris(2-carboxyethyl)phosphine) strongly enhanced the catalytic activity of P450 4A11, but not of 10 other human P450s tested. Conversely, added H2O2 attenuated P450 4A11 catalytic activity. Catalytic roles of five of the potentially eight implicated Cys residues of P450 4A11 were eliminated by site-directed mutagenesis. Using an isotope-coded dimedone/iododimedone-labeling strategy and mass spectrometry of peptides, we demonstrated that the heme-thiolate cysteine (Cys-457) is selectively sulfenylated in an H2O2 concentration-dependent manner. This sulfenylation could be reversed by reducing agents, including dithiothreitol and dithionite. Of note, we observed heme ligand cysteine sulfenylation of P450 4A11 ex vivo in kidneys and livers derived from CYP4A11 transgenic mice. We also detected sulfenylation of murine P450 4a12 and 4b1 heme peptides in kidneys. To our knowledge, reversible oxidation of the heme thiolate has not previously been observed in P450s and may have relevance for 20-HETE-mediated functions.


Antineutrophil cytoplasmic antibodies in patients with Graves' disease: association of antimyeloperoxidase autoantibodies with propylthiouracil therapy.
Abstract Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitic disorders have been reported in patients with Graves' disease during propylthiouracil (PTU) therapy. To investigate whether ANCA are found in serum samples from patients with Graves' disease, and whether PTU therapy is associated with ANCA positivity, levels of serum ANCA were examined in Graves'-disease patients receiving either PTU (n = 49) or 1-methyl-2-mercaptoimidazole (methimazole, MMI) (n = 50), and in untreated Graves'-disease patients (n = 32) by enzyme-linked immunosorbent assay (ELISA). Serum samples from patients with Hashimoto's thyroiditis (n = 46) were also analyzed. Antimyeloperoxidase (MPO) autoantibodies (MPO-ANCA) were present in 10 (20.4%) of 49 Graves'-disease patients receiving PTU therapy, whereas MPO-ANCA were not detected in Graves'-disease patients receiving MMI, in untreated Graves'-disease patients, or in Hashimoto's thyroiditis patients. The MPO-ANCA-positive sera showed a perinuclear staining pattern which was detected by indirect immunofluorescence microscopy using a human polymorphonuclear leukocyte-cytospin preparation. Furthermore, Western blot analysis revealed that MPO-ANCA in the Graves'-disease patients, as well as MPO-ANCA in patients with idiopathic pauci-immune necrotizing and crescentic glomerulonephritis, recognize the 105-kD protein of native MPO. These results indicate that MPO-ANCA in Graves'-disease patients are strongly associated with PTU therapy, and not simply related to the autoimmune thyroid disease. This study also suggests that the presence of MPO-ANCA alone may not be sufficient for the development of vasculitic disorders.


Rapid Genetic Adaptation during the First Four Months of Survival under Resource Exhaustion.
Many bacteria, including the model bacterium Escherichia coli can survive for years within spent media, following resource exhaustion. We carried out evolutionary experiments, followed by whole genome sequencing of hundreds of evolved clones to study the dynamics by which E. coli adapts during the first 4 months of survival under resource exhaustion. Our results reveal that bacteria evolving under resource exhaustion are subject to intense selection, manifesting in rapid mutation accumulation, enrichment in functional mutation categories and extremely convergent adaptation. In the most striking example of convergent adaptation, we found that across five independent populations adaptation to conditions of resource exhaustion occurs through mutations to the three same specific positions of the RNA polymerase core enzyme. Mutations to these three sites are strongly antagonistically pleiotropic, in that they sharply reduce exponential growth rates in fresh media. Such antagonistically pleiotropic mutations, combined with the accumulation of additional mutations, severely reduce the ability of bacteria surviving under resource exhaustion to grow exponentially in fresh media. We further demonstrate that the three positions at which these resource exhaustion mutations occur are conserved for the ancestral E. coli allele, across bacterial phyla, with the exception of nonculturable bacteria that carry the resource exhaustion allele at one of these positions, at very high frequencies. Finally, our results demonstrate that adaptation to resource exhaustion is not limited by mutational input and that bacteria are able to rapidly adapt under resource exhaustion in a temporally precise manner through allele frequency fluctuations.


Effects of researcher follow-up of distressed subjects: tradeoff between validity and ethical responsibility.
Researchers studying depression often encounter research participants in serious preexisting distress. Examining investigators' ethical responsibilities to these subjects, Stanton and New (1988) found that depression researchers reported actions that ranged from doing nothing to contacting both the distressed subject and a significant other. By experimentally manipulating consent form information regarding potential treatment referral, we examined whether subjects (n=357) adjusted their responses on depression measures as a function of the level of follow-up they expected to receive. Results reveal that subjects who potentially could receive the most intrusive intervention (i.e., experimenter contact with the subject and a significant other) were less likely to report depressive symptoms than were subjects who anticipated less intrusive follow-up. Willingness to report depressive symptoms in particular conditions varied in part as a function of subject sex. Thus, ethical safeguards used in studies with subjects in preexisting distress may have consequences for the validity of self-report depression measures.


Compressive correlation imaging with random illumination.
Achieving high rates and high resolution in noisy conditions is a main desiderate for computational imaging. Here, we demonstrate both numerically and experimentally that binary illumination based on spatially random distributions provides superior imaging capabilities at high compression ratios while operating in noisy environments. The proposed method permits decreasing the time for image formation without adding complexity to the imaging system or compromising the resolution.


[Not Available].
The development of dental services in the Bulgarian army is traced from its foundation up to the last world war. The first dental services (three) were founded in 1911, whilst in 1914 they became twelve. During the Balkan war the dental service in our army was non-existant. During world war one dentists were mobilized in hospitals and regiments and were obliged to work with their own instrumentarium and materials. During world war two, the first dental offices are being set out with the appointment of permanent dentists in divisional (battalion) hospitals, regiments and in the air force. For the first time during the great patriotic war the soldiers of the Bulgarian army are provided with specialized and organized dental assistance.