6-Hydroxy-5,7-dimethoxy-flavone suppresses the neutrophil respiratory burst via selective PDE4 inhibition to ameliorate acute lung injury.
Over-activated neutrophils produce enormous oxidative stress and play a key role in the development of acute and chronic inflammatory diseases. 6-Hydroxy-5,7-dimethoxy-flavone (UFM24), a flavone isolated from the Annonaceae Uvaria flexuosa, showed inhibitory effects on human neutrophil activation and salutary effects on lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice. UFM24 potently inhibited superoxide anion (O2•-) generation, reactive oxidants, and CD11b expression, but not elastase release, in N-formyl-l-methionyl-l-leucyl-l-phenylalanine (fMLF)-activated human neutrophils. However, UFM24 failed to scavenge O2•- and inhibit the activity of subcellular NADPH oxidase. fMLF-induced phosphorylation of protein kinase B (Akt) was inhibited by UFM24. Noticeably, UFM24 increased cyclic adenosine monophosphate (cAMP) concentration and protein kinase (PK) A activity in activated human neutrophils. PKA inhibitors significantly reversed the inhibitory effects of UFM24, suggesting that the effects of UFM24 were through cAMP/PKA-dependent inhibition of Akt activation. Additionally, activity of cAMP-related phosphodiesterase (PDE)4, but not PDE3 or PDE7, was significantly reduced by UFM24. Furthermore, UFM24 attenuated neutrophil infiltration, myeloperoxidase activity, and pulmonary edema in LPS-induced ALI in mice. In conclusion, our data demonstrated that UFM24 inhibits oxidative burst in human neutrophils through inhibition of PDE4 activity. UFM24 also exhibited significant protection against endotoxin-induced ALI in mice. UFM24 has potential as an anti-inflammatory agent for treating neutrophilic lung damage.


The current situation of the HIV/AIDS epidemic in Indonesia.
Until 1999 the known prevalence of HIV in Indonesia was low, except for isolated geographic groups exposed to Thai fisherman. Since then, the prevalence among injection drug users in rehabilitation centers in Jakarta has risen rapidly to approximately 45-48%, according to surveys in 2001. By 2002 the prevalence had risen to 8-17% among female sex workers, 22% among transvestite sex workers, and 4% among other male sex workers. Condom use is low in all groups, and there is considerable sexual mixing between risk groups. Surveys suggest that an increasing proportion of adolescents use drugs and have had sexual intercourse. Thus, although the epidemic in Indonesia is currently in the World Health Organization-defined "concentrated stage," all the ingredients for rapid spread are present. Intensive effective intervention strategies--condom use and clean needle use promotions--need to be implemented, especially in the high-risk groups, if a more serious epidemic is to be averted.


Comparative Performance Evaluation of Personal Protective Measures and Antiviral Agents Against SARS-CoV-2 Variants: A Narrative Review.
Scientists identified SARS-CoV-2 in December 2019 in Wuhan city of China. Soon after its identification, Covid-19 spreads almost everywhere. The World Health Organization (WHO) declared the Covid-19 outbreak as a pandemic on March 11, 2020. Countries are facing multiple waves due to the different variants of the coronavirus. Personal preventive measures, vaccines, and antiviral drugs are the approaches to control Covid-19. However, these approaches are being implemented in different countries at different levels because of the availability of personal protective measures and antiviral agents. The objective of this study was to evaluate the effectiveness of practicing measures to fight the Covid-19 pandemic. Here we searched relevant literature from PubMed and Scopus using the keywords such as personal protective measures, antiviral agents, and vaccine effectiveness. According to the present findings, protective measures were found comparatively less effective. Nevertheless, these measures can be used to limit the spreading of Covid-19. Antiviral agents can reduce the hospitalization rate and are more effective than personal protective measures. The most effective strategy against Covid-19 is early vaccination or multiple vaccination dose. The respective authorities should ensure equal distribution of vaccines, free availability of antiviral drugs, and personal protective measure in poor and developing countries. We recommend more studies to describe the effectiveness of practicing preventive measures and antiviral agents against recent variants of the coronavirus.


Parameters and techniques to determine intestinal health of poultry as constituted by immunity, integrity, and functionality.
The intestinal microflora lives in intimate contact with its surrounding intestinal wall and the bacteria can exert beneficial or deleterious effects on the host, depending on whether they are classified as probiotics or as pathogens. The interaction is determined on one hand by characteristics of the microorganisms, and on the other hand by characteristics of the intestinal wall. Together they determine the health status of the intestine. This review describes parameters and techniques (with advantages and disadvantages) available for poultry to identify the characteristics of the intestinal health, as constituted by three components: immunity, integrity, and functionality. To investigate intestinal immunity, in situ detection of various cell populations of the immune system with specific monoclonal antibodies using immunocytochemical staining is a reliable, semi-quantitative method. In vitro assays to measure functional aspects of T lymphocytes, B lymphocytes, plasma cells, natural killer cells, macrophages, and phagocytes are applicable to intestinal wall tissue. For investigation of intestinal integrity, in situ detection of villous height and crypt depth and their ratio, and villus arrangement is still an easy, routine histological method. In addition, expression levels of specific molecules, such as E-cadherin, different growth factors, and trefoil factor, seem promising parameters. To investigate functionality of the intestine, the permeability can be measured as the rate of transport of tracer molecules across the epithelial surface. Furthermore, determination of the level of mucus secretion and its composition are a valuable tool. These parameters for immunity, integrity and functionality, or a combination thereof, are indispensable to investigate the influence of intestinal microorganisms on intestinal health.


Self-report measures for use with children: a review and comment.
This article underscores the need for self-report instruments for children to complement the teacher and parent questionnaires traditionally used to assess various aspects of children's psychological lives. Some of the problems inherent in using teachers, parents, and children as informants are delineated. Many self-report instruments, in particular those that are used to assess children's self-concept, anxiety, depression, and personality, are reviewed. The Children's Self-Report Questionnaire (SRQ) was designed to assist in the diagnosis and detection of psychological deviance in 7- to 12-year-old children. The SRQ is easily administered, has broadly based norms, and has acceptable reliability and validity. The SRQ can be used as an aid to both research and clinical assessment and may provide insight into the inner world of the child.


[Laparoscopic versus open right hemicolectomy: 5-year oncology results].
Laparoscopic right hemicolectomy has developed less markedly than rectosigmoid resection, probably because of the more complicated regional anatomy and greater difficulty in performing an adequate regional lymphectomy. The aim of the present study was to analyse our 5-year experience with laparoscopic right hemicolectomy. Twenty patients were enrolled with non-metastatic, non-infiltrating right colonic cancer, treated laparoscopically and compared to a group well matched for age, sex, comorbidity and stage of disease, treated laparotomically. The duration of the laparoscopic procedures was slightly longer, but intraoperative blood loss, passage of flatus and hospital stay were reduced compared to the laparotomic procedure. Morbidity was similar and there was no 30-day mortality in either group. Specimen length and number of harvested lymph nodes were similar and the 5-year cumulative survival curves showed no statistically significant difference (72.5% versus 72.2%). Our experience shows that laparoscopic right hemicolectomy is a safe, effective and oncologically adequate procedure, comparable in all respects to open hemicolectomy, but with all the advantages of the minimally invasive technique. Yet, it remains a complex surgical procedure, requiring skill and a long learning curve. Further studies, possibly prospective and randomised, are necessary to define the exact role of this technique for the treatment of non-metastatic, non-infiltrating right colonic cancer.


Distribution, subcellular localization and identity of immunoreactive alpha-melanotropin in the pituitary gland and brain.
In homogenates of adult human or rat hypothalamic tissue, immunoreactive alpha-MSH (alpha-MSHi) is concentrated in synaptosomes, suggesting that it is localized in neurons. This conclusion is supported by immunohistochemical results on the localization of alpha-MSHi in the brain. The function of alpha-MSHi in the hypothalamus is undefined but the amount of alpha-MSH in this tissue increases in young rats and decreases in old rats. There is little alpha-MSHi in pituitary glands from human abortuses before the 15th gestational week. Thereafter the amount of alpha-MSHi in the anterior and neurointermediate lobes increases appreciably. When acetic acid extracts of each lobe were analysed by high-pressure liquid chromatography the alpha-MSHi in extracts of the anterior lobe had a retention time equal to that of desacetyl alpha-MSH; little if any alpha-MSHi had a retention time identical to that of desacetyl alpha-MSH; alpha-MSH, if present in these extracts, appeared to be a minor component. A similar analysis of extracts of adult human hypothalamic tissue yielded results suggesting that the alpha-MSHi in this tissue is also attributable largely to desacetyl alpha-MSH.


Spring flowering habit in field pennycress (Thlaspi arvense) has arisen multiple independent times.
Field pennycress (Thlaspi arvense L.) is currently being developed as a new cold-tolerant oilseed crop. In natural populations, pennycress, like many Brassicaceae relatives, can exhibit either a winter or spring annual phenotype. Pennycress is a diploid relative of Arabidopsis thaliana, a model species that has been used to study many adaptive phenotypes, including flowering time and developmental timing. In Arabidopsis and other Brassicaceae species, mutations in negative regulators of flowering, including FLOWERING LOCUS C and FRIGIDA can cause the transition to a spring annual habit. The genetics underlying the difference between spring and winter annual pennycress lines are currently unknown. Here, we report the identification of four natural alleles of FLC in pennycress that confer a spring annual growth habit identified through whole genome sequencing, cosegregation analyses, and comparative genomics. The global distribution of these spring annual alleles of FLC suggests that the spring annual growth habit has arisen on several independent occasions. The two spring annual FLC alleles present in European accessions were only identified in North American accessions collected in southern Montana, which indicates accessions harboring these two alleles were introduced to North America, likely after pennycress became a widespread species on the continent. These findings provide new information on the natural history of the introduction and spread of spring annual pennycress accessions from Europe into North America. At the molecular level, these findings are important for the ongoing development of pennycress as a winter annual crop. An enhanced understanding of the regulation of flowering in this species should allow for the fine-tuning of flowering in commercial varieties.


Peripheral nervous system involvement complicated due to vasculitis in cases of primary Sjögren's syndrome: case studies in a single hospital and a literature review.
Abstract To determine the background features of peripheral nervous system (PNS) involvement in cases of primary Sjögren's syndrome (SS), we studied the nervous system involvement, mainly that of PNS, in patients with primary SS who were admitted to our hospital during a period of 19 years. Nine of 82 admitted patients with primary SS had PNS involvement and 12 had central nervous system (CNS) involvement. Among 182 secondary SS patients, 25 had CNS involvement, and none had PNS involvement. The nine patients with PNS involvement were older and their disease duration was shorter than those with CNS involvement and either primary or secondary SS. Four patients exhibiting active progression of PNS involvement had concomitant vasculopathy clinically that was confirmed by nerve or skin biopsy examination, with an increase in the serum C-reactive protein level. According to the literature, among 17 reported SS patients with PNS involvement, 13 had primary SS, and 13 had vasculitis as confirmed by biopsy examination. Nervous system involvement in cases of SS is not rare. PNS involvement was observed mostly in elderly patients with primary SS, and its active progression was concomitant with vasculopathy.


Life Threat and Sleep Disturbances in Adolescents: A Two-Year Follow-Up of Survivors From the 2011 Utøya, Norway, Terror Attack.
A significant number of adolescents have been exposed to traumatic life events. However, knowledge about the specific sleep disturbance that occurs in individuals after trauma exposure is predominantly based on studies of adults. This study reports specific sleep disturbance in 42 survivors of the 2011 mass shooting at a youth summer camp on the Norwegian island Utøya, mean age = 20.91 years, SD = 2.32, 62.5% females. When compared with matched controls, significantly more survivors reported having sleep disturbances, 52.4% versus 13.6%, d = 0.93, of which onset began at the time of the shooting, χ2 = 14.9, p < .001. The prevalence of insomnia, 56.3% versus 11.0%, d = 0.73; excessive daytime sleepiness, 34.4% versus 13.6%, d = 0.61; symptoms of obstructive sleep apnea, 18.8% versus 0%, d = 0.70; and frequent nightmares, 37.5% versus 2.3%, d = 0.90, were all higher in the survivors than in the controls. In a subgroup of survivors (n = 20) with psychiatric diagnoses, sleep disturbances were more prevalent than in survivors without psychiatric diagnosis. Actigraphy data revealed delayed bedtime, sleep onset, and rise time in survivors compared with controls, ts > 1.7, ps = .044 to .028. These results corroborate the effects of a life threat on the range and extent of sleep disturbances, and emphasize the need to better assess and treat sleep disorders in adolescents exposed to trauma.


Steam pretreatment of lignocellulosic material for enhanced enzymatic hydrolysis.
Pretreatment methods were compared with steam explosion, and differing views on the relative importance of mechanical and chemical effects were outlined. Hydrolysis was desirable; pyrolysis was undesirable. The effects of initial moisture content on steam consumption, mechanism and rate of heat transfer, pentosan solubilization, and subsequent glucose yield were summarized. The insignificant effect, after treatment at 240 degrees C, of 90% pressure bleed-down before explosion on subsequent simultaneous saccharification and fermentation (SSF) yields was described. Treatment at 190 degrees C with complete bleed-down (no explosion), when compared with that at 240 degrees C with explosion from full pressure, showed at least as good solubilizatoin of pentosan, enzymatic hydrolysis, and SSF but showed greater pentosan destruction for the same degree of pentosan removal. Water washing of unexploded steamed aspenwood chips was at least as efficient as that of similarly treated but exploded chips. Scanning electron micrographs of unexploded chips showed extensive rupturing of vessel pit membranes and other morphological features associated with steam-exploded wood. Neither the explosion nor the high temperatures (above 190 degrees C) are necessary.


Tightly-Coupled Vehicle Positioning Method at Intersections Aided by UWB.
Reliable and precise vehicle positioning is essential for most intelligent transportation applications as well as autonomous driving. Due to satellite signal blocking, it can be challenging to achieve continuous lane-level positioning in GPS-denied environments such as urban canyons and crossroads. In this paper, a positioning strategy utilizing ultra-wide band (UWB) and low-cost onboard sensors is proposed, aimed at tracking vehicles in typical urban scenarios (such as intersections). UWB tech offers the potential of achieving high ranging accuracy through its ability to resolve multipath and penetrate obstacles. However, not line of sight (NLOS) propagation still has a high occurrence in intricate urban intersections and may significantly deteriorate positioning accuracy. Hence, we present an autoregressive integrated moving average (ARIMA) model to first address the NLOS problem. Then, we propose a tightly-coupled multi sensor fusion algorithm, in which the fuzzy calibration logic (FCL) is designed and introduced to adaptively adjust the dependence on each received UWB measurement to effectively mitigate NLOS and multipath interferences. At last, the proposed strategy is evaluated through experiments. Ground test results validate that this low-cost approach has the potential to achieve accurate, reliable and continuous localization, regardless of the GPS working statue.


ACE-2/Ang1-7/Mas cascade mediates ACE inhibitor, captopril, protective effects in estrogen-deficient osteoporotic rats.
The local role of the renin angiotensin system (RAS) was documented recently beside its conventional systemic functions. Studies showed that the effector angiotensin II (AngII) alters bone health, while inhibition of the angiotensin converting enzyme (ACE-1) preserved these effects. The newly identified Ang1-7 exerts numerous beneficial effects opposing the AngII. Thus, the current study examines the role of Ang1-7 in mediating the osteo-preservative effects of ACEI (captopril) through the G-protein coupled Mas receptor using an ovariectomized (OVX) rat model of osteoporosis. 8 weeks after the surgical procedures, captopril was administered orally (40mgkg-1 d-1), while the specific Mas receptor blocker (A-779) was delivered at infusion rate of 400ngkg-1min-1 for 6 weeks. Bone metabolic markers were measured in serum and urine. Minerals concentrations were quantified in serum, urine and femoral bones by inductive coupled plasma mass spectroscopy (ICP-MS). Trabecular and cortical morphometry was analyzed in the right distal femurs using micro-CT. Finally, the expressions of RAS peptides, enzymes and receptors along with the receptor activator of NF-κB ligand (RANKL) and osteoprotegerin (OPG) were determined femurs heads. OVX animals markedly showed altered bone metabolism and mineralization along with disturbed bone micro-structure. Captopril significantly restored the metabolic bone bio-markers and corrected Ca2+ and P values in urine and bones of estrogen deficient rats. Moreover, the trabecular and cortical morphometric features were repaired by captopril in OVX groups. Captopril also improved the expressions of ACE-2, Ang1-7, Mas and OPG, while abolished OVX-induced up-regulation of ACE-1, AngII, Ang type 1 receptor (AT1R) and RANKL. Inhibition of Ang1-7 cascade by A-779 significantly eradicated captopril protective effects on bone metabolism, mineralization and micro-structure. A-779 also restored OVX effects on RANKL expression and ACE-1/AngII/AT1R cascade and down-regulated OPG expression and ACE-2/Ang1-7/Mas pathway. In line with the clinical observations of the bone-preservative properties following ACE-1 inhibition, local activation of ACE-2/Ang1-7/Mas signaling and suppressed osteoclastogenesis seem responsible for the osteo-preservative effect of captopril, which could offers a potential therapeutic value in treatment of disabling bone and skeletal muscular diseases.


Drugs with susceptible sites for free radical induced oxidative transformations: the case of a penicillin.
Penicillins, as bactericidal antibiotics, have been widely used to treat infections for several decades. Their structure contains both aromatic and thioether moieties susceptible to free radical oxidation. The (•)OH induced oxidation mechanism of amoxicillin was investigated by pulse radiolysis techniques and by final product analysis performed after steady-state γ-irradiation. The predominant sites of the (•)OH attack are suggested to be the thioether group, initially yielding an (•)OH adduct to the sulfur, and the aromatic ring. This adduct to the sulfur converts to sulfur radical cation, which has three competitive reaction paths: (1) by deprotonation at the adjacent carbon α-(alkylthio)alkyl radicals form, which undergo disproportionation leading presumably to sulfoxide as main product; (2) via the pseudo-Kolbe mechanism it may transform to α-aminoalkyl radicals; (3) the radical cation can be stabilized through intramolecular S.˙.O bond formation. The reaction mechanism suggests the presence of a short-living and a stabilized (via hydrogen bonding) long-living (•)OH adduct to the sulfur. The three-electron bonded dimers of amoxicillin were not formed owing to steric hindrance. Thiyl radicals were also present in equilibrium with α-aminoalkyl radicals. In the presence of dissolved oxygen, aromatic ring hydroxylation occurred along with complex reactions resulting in e.g. oxidation of the methyl groups. The formation of the sulfoxide is especially effective in the presence of dissolved oxygen, under anaerobic condition, however, it is also generated owing to H2O2 and α-(alkylthio)alkyl radicals. The thioether moiety appears to be more sensitive to oxidation compared to the aromatic ring in case of amoxicillin.


Nitric Oxide Story.
Inhaled Nitric Oxide in Persistent Pulmonary Hypertension of the Newborn. By Roberts JD, Polaner DM, Lang P, and Zapol WM. Lancet 1992; 130:435-40. Reprinted with permission.NO has vasodilatory effects on the pulmonary vasculature in adults and animals. We examined the effects on systemic oxygenation and blood pressure of inhaling up to 80 parts per million by volume of NO at fraction of inspired oxygen 0.9 for up to 30 min by six infants with persistent pulmonary hypertension of the newborn. In all infants, this treatment rapidly and significantly increased preductal oxygen saturation; in five infants, postductal oxygen saturation and oxygen tensions also increased. Inhalation of NO did not cause systemic hypotension or raise methemoglobin. These data suggest that low levels of inhaled NO have an important role in the reversal of hypoxemia due to persistent pulmonary hypertension of the newborn.


Activity of placental enzymes of carbohydrate and lipid metabolism in normal, toxemic and small-for-date pregnancies.
The specific activity of placental enzymes with a regulatory function in the pathways of glycolysis, gluconeogenesis, NADPH generation and fatty acid synthesis decrease during gestation in the rat. Similar decreases occur in the activity of enzymes of the human placenta when compared between early gestation and term, with the exception of the activity of enzymes related to gluconeogenesis which tend to increase as gestation advances. In term placentas from pregnancies complicated by preeclamptic toxemia, enzyme activities were significantly lower than those in placentas from normal pregnancies, irrespective of whether the baby was of normal weight or small-for-date. This indicates an accelerated decline in placental metabolic function in toxemia. In contrast, in placentas from nontoxemic pregnancies with small-for-date babies the enzyme activities were significantly higher than those in normal term placentas. It is suggested that the decrease in placental enzyme activity, which is associated with placental growth during the course of normal gestation, is retarded in nontoxemic pregnancies with small-for-date babies, apparently due to the arrested aging of the placenta.


Cellular senescence of renal tubular epithelial cells in renal fibrosis.
Renal fibrosis (RF) is the common pathological manifestation of virtually all chronic kidney diseases (CKD) and one of the major causes of end-stage renal disease (ESRD), but the pathogenesis of which is still unclear. Renal tubulointerstitial lesions have been identified as a key pathological hallmark of RF pathology. Renal tubular epithelial cells are the resident cells of the tubulointerstitium and play an important role in kidney recovery versus renal fibrosis following injury. Studies in recent years have shown that senescence of renal tubular epithelial cells can accelerate the progression of renal fibrosis. Oxidative stress(OS), telomere attrition and DNA damage are the major causes of renal tubular epithelial cell senescence. Current interventions and therapeutic strategies for cellular senescence include calorie restriction and routine exercise, Klotho, senolytics, senostatics, and other related drugs. This paper provides an overview of the mechanisms and the key signaling pathways including Wnt/β-catenin/RAS, Nrf2/ARE and STAT-3/NF-κB pathway involved in renal tubular epithelial cell senescence in RF and therapies targeting renal tubular epithelial cell senescence future therapeutic potential for RF patients. These findings may offer promise for the further treatment of RF and CKD.


Hydrogen sulfide-based therapeutics and gastrointestinal diseases: translating physiology to treatments.
Hydrogen sulfide (H2S) is a gaseous meditator that has various physiological and pathophysiological roles in the body. It has been shown to be an important mediator of gastrointestinal (GI) mucosal defense and contributes significantly to repair of damage and resolution of inflammation. Synthesis of H2S increases markedly after mucosal injury, and inhibition of H2S in such circumstances leads to delayed healing and exacerbated inflammation. The beneficial effects of H2S may be attributable to its ability to elevate mucosal blood flow, prevent leukocyte-endothelial adhesion, reduce oxidative stress, and stimulate angiogenesis. The use of H2S-donating agents and inhibitors of the key enzymes contributing to H2S synthesis have provided strong evidence for the importance of H2S in enhancing mucosal resistance to damage, as well as modulating inflammation and repair. In recent years, significant evidence has been generated to support the notion that these positive aspects of H2S can be exploited in drug design, particularly for arthritis, inflammatory bowel disease, and colon cancer chemoprevention. Thus novel H2S-based therapies have been shown to be effective anti-inflammatories that can promote the resolution of inflammation and accelerate the healing of GI ulcers. Encouraging results have already been seen experimentally with a mesalamine derivative and with H2S-releasing derivatives of nonsteroidal anti-inflammatory drugs.


Stimulated release of endothelin-converting enzyme is simultaneous with tissue-type plasminogen activator and decrease in coronary heart disease.
During the process of atherosclerosis the endothelium changes both structurally and functionally. We examined whether shedding of endothelin-converting enzyme (ECE), a metalloprotease responsible for endothelin production, is concomitant with tissue-type plasminogen activator (t-PA), and how atherosclerosis affects ECE release. Fourteen healthy volunteers and 24 patients with angiographically verified coronary heart disease (CHD) were investigated. ECE and t-PA releases were measured by a provocation test (20-min venous occlusion). Serum ECE activities were comparable in both groups before the venous occlusion test (in CHD patients 205 +/- 24 vs in healthy controls 204 +/- 40 pmol/ml/h, p = NS). However, delta-ECE (= the difference between, after, and before the venous occlusion test) was significantly lower in CHD patients than in controls (203 +/- 36 vs 338 +/- 43 pmol/ml/h, p = 0.02, respectively). Delta-t-PA was similar in both groups (22.3 +/- 4.4 vs 14.5 +/- 4.6 ng/ml, p = NS, respectively). Furthermore, t-PA and ECE values correlated in the CHD group in all pre-, post-venous occlusion test, and delta-venous occlusion test values (r = 0.56, p = 0.009; r = 0.62, p = 0.003; r = 0.54, p = 0.01, respectively). Vascular ECE release can be stimulated, and it is concomitant with t-PA release. A common location in endothelium may explain this simultaneous shedding. However, ECE levels do not rise in patients with CHD as markedly as in healthy patients. Atherosclerosis may explain reduced shedding of ECE.


Protective effects of ginseng and ginsenosides in the development of osteoarthritis (Review).
Osteoarthritis (OA) is a chronic inflammatory joint disease. Traditional chinese medicine provides a resource for drug screening for OA treatment. Ginseng and the associated bioactive compound, ginsenosides, may reduce inflammation, which is considered a risk factor for the development of OA. Specifically, ginsenosides may exhibit anti-inflammatory and anti-oxidative stress activities, and inhibit extracellular matrix degradation by suppressing the NF-κB and MAPK signaling pathways. Notably, specific ginsenosides, such as compound K and Rk1, may physically interact with IκB kinase and inhibit the associated phosphorylation. Thus, ginsenosides exhibit potential as therapeutic candidates in the management of OA. However, the low water solubility limits the clinical applications of ginsenosides. Numerous effective strategies have been explored to improve bioavailability; however, further investigations are still required.


Validated liquid chromatography-tandem mass spectrometry method for quantification of ticagrelor and its active metabolite in human plasma.
A rapid, simple and sensitive LC-MS/MS method was established and validated for simultaneous quantification of ticagrelor and its active metabolite AR-C124910XX in human plasma. After plasma samples were deproteinized with acetonitrile, the post-treatment samples were chromatographed on a Dikma C18 column interfaced with a triple quadrupole tandem mass spectrometer. Electrospray negative ionization mode and multiple reaction monitoring were adopted to assay ticagrelor and AR-C124910XX. Acetonitrile and 5 mΜ ammonium acetate was used as the mobile phase with a gradient elution at a flow rate of 0.5 mL/min. The method was linear in the range of 0.781-800 ng/mL for both ticagrelor and AR-C124910XX with a correlation coefficient ≥0.994. The intra- and inter-day precisions were within 12.61% in terms of relative standard deviation and the accuracy was within ±7.88% in terms of relative error. The LC-MS/MS method was fully validated for its sensitivity, selectivity, stability, matrix effect and recovery. This convenient and specific LC-MS/MS method was successfully applied to the pharmacokinetic study of ticagrelor and AR-C124910XX in healthy volunteers after an oral dose of 90 mg ticagrelor.


[Precocious puberty and ovarian follicular cysts].
Ovarian follicular cysts have been detected by ultrasound in 2 to 8 years old girls with precocious puberty, central puberty (2 cases), transient precocity (1 case) or premature menarche (1 case). Complete regression of the cysts was either spontaneous (1 case) or due to suppressive therapy. The mechanisms of precocious puberty with follicular cysts, dependent or independent of gonadotropins, and their spontaneous evolution guide both the management and the therapy with LH-RH analogues and/or aromatase inhibitors.


Venom Profiling of a Population of the Theraphosid Spider Phlogius crassipes Reveals Continuous Ontogenetic Changes from Juveniles through Adulthood.
Theraphosid spiders (tarantulas) are venomous arthropods found in most tropical and subtropical regions of the world. Tarantula venoms are a complex cocktail of toxins with potential use as pharmacological tools, drugs and bioinsecticides. Although numerous toxins have been isolated from tarantula venoms, little research has been carried out on the venom of Australian tarantulas. We therefore investigated the venom profile of the Australian theraphosid spider Phlogius crassipes and examined whether there are ontogenetic changes in venom composition. Spiders were divided into four ontogenic groups according to cephalothorax length, then the venom composition of each group was examined using gel electrophoresis and mass spectrometry. We found that the venom of P. crassipes changes continuously during development and throughout adulthood. Our data highlight the need to investigate the venom of organisms over the course of their lives to uncover and understand the changing functions of venom and the full range of toxins expressed. This in turn should lead to a deeper understanding of the organism's ecology and enhance the potential for biodiscovery.


Gemifloxacin, a fluoroquinolone antimicrobial drug, inhibits migration and invasion of human colon cancer cells.
Gemifloxacin (GMF) is an orally administered broad-spectrum fluoroquinolone antimicrobial agent used to treat acute bacterial exacerbation of pneumonia and bronchitis. Although fluoroquinolone antibiotics have also been found to have anti-inflammatory and anticancer effects, studies on the effect of GMF on treating colon cancer have been relatively rare. To the best of our knowledge, this is the first report to describe the antimetastasis activities of GMF in colon cancer and the possible mechanisms involved. Results have shown that GMF inhibits the migration and invasion of colon cancer SW620 and LoVo cells and causes epithelial mesenchymal transition (EMT). In addition, GMF suppresses the activation of NF- κ B and cell migration and invasion induced by TNF- α and inhibits the TAK1/TAB2 interaction, resulting in decreased I κ B phosphorylation and NF- κ B nuclear translocation in SW620 cells. Furthermore, Snail, a critical transcriptional factor of EMT, was downregulated after GMF treatment. Overexpression of Snail by cDNA transfection significantly decreases the inhibitory effect of GMF on EMT and cell migration and invasion. In conclusion, GMF may be a novel anticancer agent for the treatment of metastasis in colon cancer.


[Induction of anti-cancer cells and systemic immune response in hepatocellular carcinoma by OK-432].
We examined whether anti-cancer cells are induced in vivo in hepatocellular carcinoma (HCC) by OK-432. Ten patients with HCC were randomly divided into two groups. The group I patient (n = 5) served as the control. In group II (n = 5), OK-432 was preoperatively administered via the hepatic artery. Tumor infiltrating lymphocytes (TILs) were collected from resected tumors. Cytotoxicity of TILs against K562 cells and Raji cells was studied with phenotypic analysis by flow cytometry. Freshly isolated TILs, whether or not treated with OK-432, showed low cytotoxicity. When TILs were co-cultured with recombinant interleukin-2 (rIL-2), the cytotoxicity was significantly activated in the OK-432 treated group, whereas untreated TILs showed no activation. The natural killer (NK) activity and the lymphokine-activated killer (LAK) activity were depressed in group I after hepatic resection, but patients in group II had no depression. Our data indicate that LAK precursor cells are induced in TILs and the prevention of post-operative immune suppression is made possible by OK-432.


[Pneumothorax in pregnancy. Apropos of 3 cases].
We report 3 cases of pneumothorax developed during pregnancy and we compare them with the 16 cases previously published. We insist on the late occurrence of pneumothorax during pregnancy and on the possibility of vaginal delivery. Data from literature and our own experience incline us to believe that pneumothorax is not rare during pregnancy but is often misdiagnosed or unreported.


Use of antibiotics contrary to guidelines for children's lower respiratory tract infections in different health care settings.
This study aimed to evaluate antibiotic prescriptions for children with lower respiratory tract infection (LRTI) in public and private primary care clinics and in a hospital's pediatric emergency department (PED) in 2012-2013 (pre-guideline) and in 2014-2015 (post-guideline). Special attention was paid to guideline compliance, especially regarding macrolide prescriptions, which the guidelines discourage. Retrospective data of 1431 children with LRTI in November-December 2012-2015 were collected from electronic registers and checked manually. Three diagnostic groups were analyzed: community-acquired pneumonia (CAP), wheezing bronchitis, and non-wheezing bronchitis. A comparison of the pre- and post-guideline periods revealed antibiotic prescription rates of 48.7% and 48.9% (p = 0.955) for all LRTIs, respectively, and 77.6% and 71.0% (p = 0.053) for non-wheezing bronchitis. The prescription rates for all LRTIs were 24.9% in PED and 45.9% in public (p < 0.001 vs. PED) and 75.4% in private clinics (p < 0.001 vs. PED and p < 0.001 vs. public clinics). During post-guideline periods, antibiotics were prescribed for CAP less often in private (56.3%) than in public clinics (84.6%; p = 0.037) or in PED (94.3%; p < 0.001 vs. private and p = 0.091 vs. public primary clinics). Macrolide prescriptions were highest in private clinics (42.8%), followed by public primary care clinics (28.5%; p < 0.05) and PED (0.8%; p < 0.05 vs. both public and private primary care). Amoxicillin was the predominant antibiotic in public primary care and PED and macrolides in private primary care. Antibiotic prescribing for children with LRTI differed significantly between healthcare providers. CAP was undertreated and bronchitis overtreated with antibiotics in primary care, especially in the private clinics. • Clinical Treatment Guidelines tend to have modest effect on physicians' antibiotic prescribing habits. • Pediatric viral LRTIs are widely treated with unnecessary antibiotics. • Remarkable differences in antibiotic prescriptions in pediatric LRTIs between Finnish private and public providers were observed. • Overuse of macrolides was common especially in private clinics.


Neuro-ophthalmology of mitochondrial diseases.
The afferent and efferent visual pathways within the central nervous system are frequently involved in mitochondrial diseases. Neuro-ophthalmic signs figure prominently and may be the presenting or even sole manifestation of these disorders. The four most common neuro-ophthalmic abnormalities seen in mitochondrial disorders are bilateral optic neuropathy, ophthalmoplegia with ptosis, pigmentary retinopathy, and retrochiasmal visual loss.


Hypertrophy of the labia minora.
Gynecologic disorders during childhood and adolescence have received relatively little attention. Since earlier sexual activity among teenage girls is becoming more common, it is desirable that those interested in the diseases of women keep abreast of the current developments in adolescent gynecology. Two patients with congenital hypertrophy of the labia minora are presented and the treatment is discussed.


Sociotechnical probabilistic risk modeling to predict injurious falls in community living centers.
The goal of this study was to apply sociotechnical probabilistic risk assessment to prioritize risks and prevention strategies for serious injurious falls of residents in nursing homes. Risk modeling teams consisted of 26 clinical and nonclinical staff from three Department of Veterans Affairs community living centers and one state Veteran's nursing home. Participants met in groups several times to identify and assign probabilities to provider and resident at-risk behaviors and equipment failures. They identified prevention strategies for the failures that accounted for the highest levels of risk. Six scenarios were modeled: (1) transferring from bed to wheelchair, (2) propelling from bedside to bathroom, (3) transferring from wheelchair to toilet, (4) transferring from toilet to wheelchair, (5) propelling from bathroom to bedside, and (6) transferring from wheelchair to bed. The greatest paths of risk were for residents with impaired mobility and high fragility. A 26% reduction in injurious falls could be achieved by (1) reducing the number of unassisted transfers through a modest improvement in response time to alarms, (2) installing automatic brake locks on 90% of wheelchairs, (3) making the wheelchair maintenance process highly reliable, and (4) decreasing improper transfer techniques by 10%.


Lipophilic fluorescent products of free radicals.
Fluorescent pigments are the end-products of reactions involving free radical attack on biological molecules and can be formed, for example, in reactions between lipid peroxidation products, mainly unsaturated aldehydes, with free amino groups. Their characteristic emission maximum was found to be at 420-470 nm after being excited at 340-390 nm. The mechanism of their formation and chemical identity has been revealed in many in vitro studies, in which reactive aldehydes were incubated with amino group-containing molecules. Owing to their intrinsic fluorescent properties and molecular stability these products are easily measured by means of spectrofluorimetry and are used as biomarkers of oxidative stress caused by various triggers. It has been found that the fluorescent products are formed in excess in conditions linked with increased free radical production, such as atherosclerosis, Alzheimer's disease and multiple sclerosis. We searched the literature using "MEDLINE" and "Web of Science" in order to get an overview of the state of knowledge about fluorescent products of free radicals, that is, their analysis from in vitro studies, animal and human studies and their use as markers of oxidative damage. Although their chemical structure may not have been elucidated, the fluorophores formed in this way have found application as markers of oxidative stress in many animal and human studies. In vitro experiments using model reactions have given some clues as to how certain fluorescent pigments arise during oxidative reactions in vivo. Advances in analytical techniques should lead the chemical characterization of pigments of different origin to completeness.


Transient increase in telomerase activity of proliferating fibroblasts and endothelial cells in granulation tissue of the human skin.
Although granulation tissue formation is an important step for second-intention wound healing, the molecular events underlying this process are still poorly understood. To investigate the role of telomerase in the formation of granulation tissue, we measured the activity of this enzyme and determined the expression and localization of human telomerase reverse transcriptase mRNA using human skin samples. Telomerase activity in the tip of the granulation tissue where fibroblasts actively proliferate was detected at a level 5.6 +/- 1.5 times higher than that at the edge of the tissue when using a polymerase chain reaction-based telomeric repeat amplification protocol assay coupled with enzyme-linked immunosorbent assay. This, together with the findings from semiquantitative reverse transcriptase-polymerase chain reaction and in situ hybridization of human telomerase reverse transcriptase, revealed that proliferating cell nuclear antigen-positive fibroblasts and endothelial cells in the progressing granulation tissue showed de novo activation of telomerase with high human telomerase reverse transcriptase mRNA expression. This condition may be a prolongation of cellular replicative capacity taking advantage of the positive regulatory dynamics of cell growth. We conclude that the regulation of telomerase activity may play an important role in granulation tissue formation in wound healing.


Plant collagenase: unique collagenolytic activity of cysteine proteases from ginger.
Two cysteine proteases, GP2 and GP3, have been isolated from ginger rhizomes (Zingiber officinale). GP2 is virtually identical to a previously identified ginger protease GPII [K.H. Choi, and R.A. Laursen, Amino-acid sequence and glycan structures of cysteine proteases with proline specificity from ginger rhizome Zingiber officinale, Eur. J. Biochem. 267 (2000) 1516-1526.], and cleaves native type I collagen at multiple discrete sites, which are in the interior of the triple helical region of this molecule. In reaction with proline-containing peptides GP2 shows preference for Pro in the P2 position, and at least 10-fold higher efficiency of hydrolysis than papain. Comparison of models of GP2 and GP3 with the crystal structure of papain shows that the three enzymes have different S2 pocket structures. The S2 pocket in GP2 and GP3 is half the size of that of papain. GP2 is the only reported plant cysteine protease with a demonstrated ability to hydrolyse native collagen. The results support a role for ginger proteases as an alternative to papain, in commercial applications such as meat tenderization, where collagen is the target substrate.


Generation of different mode-locked states in a Yb-doped fiber laser based on nonlinear multimode interference.
We demonstrated an ultrafast Yb-doped fiber laser with a single mode fiber-graded index multimode fiber-single mode fiber (SMF-GIMF-SMF) structure based saturable absorber. The GIMF was placed in the groove of an in-line fiber polarization controller to adjust its birefringence, enabling the SMF-GIMF-SMF structure to realize efficient saturable absorption based on nonlinear multimode interference without strict length restriction. By adjusting two intra-cavity polarization controllers, stable dissipation solitons and noise-like pulses were achieved in the 1030 nm waveband with pulse durations of 10.67 ps and 276 fs, respectively. We also realized Q-switched mode-locked pulses in the same fiber laser cavity. By the dispersive Fourier transform method, the real-time spectral evolution in the buildup process of the Q-switched mode-locked state was captured, which showed that the continuous-wave in this laser could gradually evolved into the stable Q-switched mode-locked pulses through unstable self-pulsation, relaxation oscillation and rogue Q-switching stage. To the best of our knowledge, our work reveals the buildup dynamics of the Q-switched mode-locked operation in a fiber laser for the first time. And we also studied the real-time spectral evolution of the stable Q-switched mode-locked pulses, which exhibited periodic breathing property.


[«Sulfonamide allergy» - which drugs must patients avoid?].
Allergic reactions to sulfonamide antibiotics are common. A number of other drugs (for example diuretics, anti-diabetic drugs, cyclooxygenase-2 inhibitors and triptans) are also chemically speaking sulphonamides, and many of these are considered to be contraindicated in patients who have experienced an allergic reaction to sulfonamide antibiotics. What is the risk of allergic cross-reactivity between different sulfonamides and to what extent must this be taken into account in clinical practice?


Association of functional COMT Val108/Met polymorphism with smoking cessation in a nicotine replacement therapy.
Nicotine replacement treatment (NRT) can be efficacious for smoking cessation, but used by only a minority of smokers in China. Pharmacogenetic matching may improve treatment outcomes for NRT in subgroups of smokers. We evaluated the efficacy and safety of sublingual nicotine tablets (SNT) for smoking cessation and the association of catechol-O-methyltransferase (COMT) genotype with efficacy in this smoking cessation trial among Chinese smokers. We conducted a double-blind, placebo-controlled, 8-week trial of SNT with a follow-up at week 12 among 250 Chinese smokers. Efficacy and safety were evaluated at day 4 and weeks 2, 4, 6, 8, and 12. Abstinence was biochemically verified by exhaled carbon monoxide (CO) and urine cotinine. The COMT Val108Met genotype was determined as a restriction fragment length polymorphism. Our results showed that the success rates for complete abstinence were greater for active versus placebo treatments at 8 weeks (48 vs. 17 %) and 12 weeks (52 vs. 19 %) (both p < 0.0001). Craving was significantly reduced from week 2 on active treatment compared to placebo. Adverse events were mild and tolerable. We found a genotype by treatment interaction at 12 weeks with greater abstinence rates in the COMT Val/Val (50 vs. 15 %) than the Met/Val + Met/Met genotypes (46 vs. 25 %). We found that SNT significantly increased smoking abstinence, reduced craving and was well tolerated, and the COMT Val/Val genotype was associated with a greater improvement in smoking cessation.


Transient foreign accent syndrome.
Foreign accent syndrome (FAS) is a poorly understood and studied syndrome as it is indeed a rare entity. Since its first description in 1907 by French neurologist Pierre Marie involving a patient who presented with an Alsatian accent, there are approximately only 60 cases reported in the literature. The majority of such cases of FAS have been secondary to cerebrovascular accidents. Of the cases in the literature, none report such a transitory nature of FAS. In this particular case, a 55-year-old male presented with a foreign accent. This FAS was triggered by ischemia and was reversed after a seizure, the first reported in the literature.


Immunotherapy with autologous dendritic cells and tumor-specific synthetic peptides for synovial sarcoma.
Synovial sarcoma in an 11-year-old Japanese girl relapsed 5 months after autologous stem cell transplantation. Autologous dendritic cells (DCs) were generated from her peripheral blood mononuclear cells using granulocyte/macrophage colony-stimulating factor and IL-4. Dendritic cells were pulsed with synthetic peptides containing a junctional region of SYT-SSX2 fusion protein generated by t(X;18) and were administered once per week. No side effects were observed. Growth of metastatic nodules in the lung was temporally suppressed. The delayed-type hypersensitivity responses in skin were enhanced to tumor lysate but not to peripheral blood mononuclear cell lysate. The CD3+ cells cultured with pulsed DCs lysed tumor cells in vitro. Immunotherapy using DCs and tumor-specific peptides may be a safe approach in the treatment of childhood cancer.


Growth factor activity of endothelin on vascular smooth muscle.
Endothelin is a novel peptide secreted by endothelial cells, the vasoconstrictor effects of which appear dependent on the activation of phospholipase C. We examined in tissue culture its potential as a growth factor for vascular smooth muscle. In quiescent cultures of rat aortic smooth muscle cells, endothelin rapidly elevated levels of c-fos and c-myc mRNA. Peak effects on c-fos mRNA occurred between 15 and 30 min and were completely gone after 2 h. The elevation in c-fos mRNA was, in part, dependent on protein kinase C, since phorbol myristate acetate (PMA) also elevated c-fos mRNA and further increased c-fos mRNA expression by endothelin, but the effects were not additive. Furthermore, the endothelin-induced elevation in c-fos mRNA was attenuated but not abolished in protein kinase C-depleted cells. Maximum levels of c-myc mRNA occurred between 15 and 30 min after exposing the cells to endothelin and persisted for at least 6 h. The effects of simultaneous addition of endothelin and PMA on c-myc mRNA levels were essentially similar to those observed with c-fos mRNA. [3H]thymidine incorporation into DNA occurred 8 h after exposing the cells to endothelin. The mitogenic effect of endothelin was smaller than that observed with either fetal calf serum or epidermal growth factor and was dependent on both pertussis toxin-insensitive and -sensitive pathways. Sensitivity to the latter pathway did not appear dependent on attenuation of phospholipase C activity, since neither peak intracellular calcium concentrations nor c-fos mRNA levels were reduced in pertussis toxin-treated cells.(ABSTRACT TRUNCATED AT 250 WORDS)


Radical irradiation with the split-course technique in carcinoma of the lung.
The possible advantages of a split-course of irradiation in the treatment of patients with locally advanced and/or inoperable carcinoma of the lung were explored in over 200 cases. The patients were separated into two groups with different prognostic factors: Group A, patients with well-differentiated tumors confined to the lung and mediastinum; and Group B, cases with anaplastic tumors and/or supraclavicular metastases, bone erosion, or superior venal caval syndrome. The treatment consisted of 5500-6000 rads tumor dose in 20 to 24 fractions over a period of 7 to 8 weeks with a rest interval of 2 to 4 weeks in the middle. The 3- and 5-year survival figures, 19% and 16%, respectively, in Group A cases, along with the excellent tolerance, suggest that the split-course approach has definite advantages.


Lactase phlorizin hydrolase synthesis is decreased in protein-malnourished pigs.
We have examined the effect of protein malnutrition on brush border (BB) lactase phlorizin hydrolase (LPH) synthesis in young pigs. Two groups of four 3-wk-old pigs were fed diets containing either 19 g soy protein, 63 g carbohydrate and 5 g fat per 100 g diet (a protein-sufficient diet) or 3 g soy protein, 85 g carbohydrate and 5 g fat per 100 g diet (a protein-deficient diet). After 8 wk of consuming the diets, pigs were infused intravenously with 2H3-leucine for 8 h, then killed. The jejunum was collected for measurement of lactase activity, LPH mRNA abundance and the rate of LPH post-translational synthesis. Lactase activities did not differ between groups (mean 8.1 +/- 1.2 micromol x min(-1) x g mucosa(-1)). LPH mRNA abundance relative to elongation factor-1alpha mRNA (the constitutive/reference mRNA) was significantly (P < 0.05) higher in well-nourished pigs (0.36 +/- 0.03%) than in protein-malnourished pigs (0.21 +/- 0.02%). The rate constants of BB LPH post-translational synthesis were also significantly higher in the well-nourished (103 +/- 9% x d(-1)) than in the protein-malnourished pigs (66 +/- 8% x d(-1)). Further, the absolute synthesis rate of BB LPH, a measure of the amount of enzyme synthesized per gram of tissue, was significantly higher in well-nourished than in protein-malnourished pigs (in arbitrary units, 892 +/- 90 vs. 450 +/- 34, respectively). Thus, protein malnutrition affects both LPH mRNA abundance and post-translational processing in young pigs.


Factors contributing to the emulsification of intraocular silicone and fluorosilicone oils.
Silicone oil (SiO) and fluorosilicone oil (FSiO) are used as vitreous substitutes during retinal detachment surgery. Emulsification of these oils causes complications in oil-injected eyes. One factor contributing to emulsification is interfacial tension (gamma i) of the oils. In general, the lower the gamma i, the more easily the oils are emulsified. We measured the gamma i of SiO and FSiO by the ring method at 37 degrees C; corrected the measured values by the Harkins-Jordan table or the Zuidema-Waters equation; and found that the gamma i between the oils and liquefied bovine vitreous was low compared with the gamma i between the oils and water (eg, gamma i of 1000 centistokes [cs]SiO against liquefied vitreous and water was 16.0 and 42.8 dyne/cm, and that of 1000 cs FSiO was 14.7 and 38.7 dyne/cm, respectively). When SiO or FSiO and liquefied vitreous were shaken in a partially filled vial, both oils were emulsified regardless of viscosity and purity. However, when the vial was filled completely (a situation in which the hydrodynamic condition of the oils may be similar to that in the eye), SiO of 1000 and 12,500 cs and FSiO of 10,000 cs did not emulsify, although FSiO of 1000 cs did emulsify. SiO was less emulsified than FSiO of the same viscosity, possibly because the smaller density difference between SiO and intraocular fluids makes agitation difficult compared with FSiO. High viscosity of the oils restricted mechanical emulsification, which was not prevented by eliminating low-molecular-weight components of the oils. Residual catalysts may relate to spontaneous emulsification, which was observed occasionally with high-viscosity SiO in water.


Glycemic management of diabetes by insulin therapy.
Recent technological innovations as insulin analogue formulation, devices for insulin delivery and glucose monitoring have allowed diabetic patients to improve their glycemic control and decrease their level of burden due to diabetes. Intensive insulin therapy via insulin pens, subcutaneous or intraperitoneal insulin infusions using pumps instead of vials and syringes, are associated with improved absorption reproducibility, HbA1c levels, reduced risk of hypo- or hyperglycemia, and increased quality of patient's life. These currently used systems are discussed in this review as well as the future of exogenous insulin therapy: closed loop system, the artificial pancreas, and oral insulin delivery. Glucose homeostasis is directly linked to glycemic regulated by portal insulin administration, thus endogenous insulin therapy might be the most promising treatment to "cure" diabetes. Consequently, pancreas and islet transplantation, and the bioartificial pancreas are described.


The Irish organic food market: shortfalls, opportunities and the need for research.
In 2009 the Irish organic food market was forecasted to grow from €120 m to €239 m by 2013; however, recent figures set its value at just €90 m. An estimated 70% of this market is imported. Surveys of Irish consumers reveal that 66% of consumers prefer to buy local produce and most organic consumers are buying organic at supermarkets. This evidence reveals that Irish producers must trade at supermarkets, and promote 'local produce' to ensure their produce reach the majority of buyers. Seventy-eight % of organic rejecters state price and 21% state unawareness of the benefits as reasons for not buying organic. Many Irish consumers are buying organic food on the perceived belief that it is healthier, safer and tastes better; however, a review of studies on organic versus conventional foods in terms of health benefits, safety and sensory quality has shown that existing data is limited in scope and fails to show a clear trend. The review concludes with the need for a comprehensive study of a range of organic and conventional foods available to the Irish consumer in order to determine if differences in organic cultivation result in statistically significant differences in health linked compounds and sensory quality.


Bibliography of clinical research in malaysia: methods and brief results.
This article describes the methodology of this bibliography. A search was conducted on the following: (1) bibliographic databases (PubMed, Scopus, and other databases) using search terms that maximize the retrieval of Malaysian publications; (2) Individual journal search of Malaysian healthrelated journals; (3) A targeted search of Google and Google Scholar; (4) Searching of Malaysian institutional repositories; (5) Searching of Ministry of Health and Clinical Research Centre website. The publication years were limited to 2000- 2013. The citations were imported or manually entered into bibliographic software Refworks. After removing duplicates, and correcting data entry errors, PubMed's Medical Subject Headings (MeSH terms) were added. Clinical research is coded using the definition "patient-oriented-research or research conducted with human subjects (or on material of human origin) for which the investigator directly interacts with the human subjects at some point during the study." A bibliography of citations [n=2056] that fit the criteria of clinical research in Malaysia in selected topics within five domains was generated: Cancers [589], Cardiovascular diseases [432], Infections [795], Injuries [142], and Mental Health [582]. This is done by retrieving citations with the appropriate MESH terms, as follow: For cancers (Breast Neoplasms; Colorectal Neoplasms; Uterine Cervical Neoplasms), for cardiovascular diseases (Coronary Disease; Hypertension; Stroke), for infections (Dengue; Enterovirus Infections, HIV Infections; Malaria; Nipah Virus; Tuberculosis), for injuries (Accidents, Occupational; Accidents, Traffic; Child Abuse; Occupational Injuries), for mental health (Depression; Depressive Disorder; Depressive Disorder, Major; Drug Users; Psychotic Disorders; Suicide; Suicide, Attempted; Suicidal Ideation; Substance- Related Disorders).


Three-dimensional modeling of middle ear biomechanics and its applications.
This study investigated whether combined technologies of finite element (FE) analysis and three-dimensional reconstruction of human temporal bones could be used to construct a computational model, useful in describing normal and pathologic middle ear sound conduction. FE models for biologic systems have been used in ear biomechanics. Three-dimensional reconstructions have also been made, but not in combination with FE modeling and laser interferometry measuring of human temporal bones. Furthermore, an FE model for the human middle ear with its ossicular attachments has not been reported on the basis of temporal bone histologic sections and morphometric reconstruction, to the authors' best knowledge. Because of the size, variability, and complexity of the middle ear, accurate morphologic data and boundary conditions are necessary for accurate FE modeling. A fresh temporal bone was decalcified, embedded in celloidin, sectioned and stained, scanned, and digitized, and the normal middle ear was reconstructed. The histologic sections were used to construct a computer-aided design model with ligaments, muscles, and tendons as boundary conditions. The data thus obtained were converted into an FE mechanical model that was validated by comparison with displacements obtained by laser Doppler interferometry on 17 fresh human temporal bones. An FE model was generated, demonstrating dynamic behavior that moderately approximated the laser interferometric data from human temporal bones receiving 90-dB sound pressure level auditory frequencies at the tympanic membrane. Accurate FE modeling, incorporating both morphometric and interferometric performance data, predicted both normal and pathologic mechanical performance of the human ossicular chain.


[Effect of moxisylyte on the lower urinary tracts (2). Effect on the urethra in anesthetized dogs].
Effect of moxisylyte on the lower urinary tracts was studied with the urethral pressure profile (UPP) and balloon method in anesthetized female dogs. In the UPP, moxisylyte produced relaxation in both the proximal and distal urethras. The relaxation effects of prazosin and bunazosin on the distal urethra was weaker than on the proximal urethra. In the balloon method, moxisylyte, prazosin, bunazosin and phentolamine caused a decrease in urethral pressure dose-dependently. The ID25 values of moxisylyte, prazosin, bunazosin and phentolamine were 23.4, 0.43, 0.76 and 33.1 micrograms/kg, respectively. In the balloon method, moxisylyte noncompetitively antagonized phenylephrine induced contraction of the urethra at high doses, whereas prazosin, bunazosin, phentolamine and yohimbine competitively antagonized phenylephrine induced contraction of the urethra. These results suggest that moxisylyte relaxes both the proximal and distal urethras due to alpha 1-adrenoceptor antagonistic and direct urethral smooth muscle relaxant actions. Therefore, moxisylyte is useful for the therapeutic treatment of micturitional disorder.


Implementation of the European Working Time Directive in neurosurgery reduces continuity of care and training opportunities.
Implementation of the European Working Time Directive (EWTD) raises questions about reduced surgical training opportunities and lost continuity of patient care. We studied the effect that the EWTD has had in these areas for residents in the neurosurgical unit at St. George's Hospital, London, UK. Case notes for 50 emergency and 50 elective operative admissions were randomly selected before and after implementation of an EWTD compliant resident roster (total, 200 episodes). Each was objectively scored for continuity of care from the operating surgeon. Rosters from 3 months before and after implementation were compared to assess training opportunities available. A significant reduction was observed in continuity of emergency care following introduction of the EWTD compliant roster (P < 0.009). The same proportion of residents consented and operated on elective cases; however, a significant reduction in continuity of postoperative care was observed (P < 0.0001). Resident training opportunities were substantially affected with reduced involvement in outpatient (72% vs. 60%) and operating sessions (79% vs. 63%) with their nominated consultant. The EWTD has had a marked adverse impact on continuity of care for neurosurgical patients at St. George's Hospital. Residents' training opportunities were reduced.


Eyelid margin basal cell carcinoma managed with full-thickness en-face frozen section histopathology.
To determine the tumor control rate of basal cell carcinoma (BCC) of the eyelid margin managed by full-thickness eyelid resection with en-face frozen section-controlled margins and primary reconstruction of the defect. This is a retrospective, consecutive, noncomparative, longitudinal interventional case series from a single institution. A review of medical records of all patients with BCC involving the eyelid margin treated by full-thickness en-face frozen section histopathology between June 1997 and June 2011 was conducted. All cases were managed with gross full-thickness resection of the eyelid margin tumor with subsequent reconstruction. Intraoperative frozen section histopathology was performed on additional 1-mm thick medial, lateral, and inferior/superior specimens in a full-thickness en-face fashion. The main outcome measure was rate of recurrence over the follow-up period. Additional data collected included patient demographics, lesion site and size, histopathology, reconstructive technique, and postoperative complications. The review resulted in a total of 74 patients with 77 lesions. Of these, 45 lesions had a minimum 5-year follow up. Those cases that involved the lacrimal system were excluded resulting in a total of 43 cases for analysis, which had a mean follow up of 6.4 years (range, 5.0-13.0). Three cases (6.9%) represented a recurrent BCC, while all other cases were primary BCCs. The histopathological subtypes included nodular (65.1%), infiltrative (18.6%), and superficial (16.3%). There were no cases of recurrence (100% cure rate) over the follow-up period. Most defects (88.4%) were reconstructed by direct closure or a temporal rotation flap. The only complication noted was the development of a hypertrophic scar in 1 patient that resolved with conservative management. In the total series of 77 lesions, the mean follow-up period was 4.5 years (range, 0.5-13.0). One recurrence (1.3%) was detected after 1.1 years for an infiltrative BCC measuring 10.0 mm in diameter that involved the lacrimal system. Eyelid margin BCC can be managed effectively with full-thickness en-face frozen section-controlled excision and primary reconstruction of the defect. The high cure rate compares favorably with other excision techniques such as Mohs micrographic surgery, with the advantages of a single operation and excellent reconstructive result.


Randomized trial of varying mineral intake on total body bone mineral accretion during the first year of life.
The effect of varying mineral intakes on total body bone mass accretion during the first year of life in healthy full-term infants is unknown. The purpose of this study was to determine whether total body bone mass accretion during the first year of life was influenced by the calcium and phosphorus intake of an infant and whether early differences in bone accretion persist through 1 year of age. This prospective, randomized trial was conducted in two phases. In phase I, 67 infants were randomized within the first 2 weeks of life into either a low (439 mg of calcium per liter and 240 mg of phosphorus per liter) or moderate (510 mg of calcium per liter and 390 mg of phosphorus per liter) mineral-containing formula feeding group. An additional group of 34 human milk-fed (low mineral) infants also was enrolled. Phase II involved an additional randomization of all infants at 6 months of age into moderate-mineral formula (see above), high-mineral formula (1350 mg of calcium per liter and 900 mg of phosphorus per liter), or cow milk (1230 mg of calcium per liter and 960 mg of phosphorus per liter) feeding group. Anthropometric measurements, nutrient intake, and total body bone mineral content (BMC) by dual-energy x-ray absorptiometry were measured at 1, 3, 6, 9, and 12 months. During the first 6 months, the moderate-mineral group had a greater increase in weight (3.42 +/- 0.62 kg) compared with the human milk group (2.93 +/- 0.56 kg); the low-mineral group (3.19 +/- 0.62 kg) was intermediate. Bone mass accretion differed in a similar direction, with the moderate-mineral feeding group having a greater increase than the human milk group and the low-mineral group being intermediate of the two. Including weight, length, and bone area as covariates, both the low-mineral formula- and human milk-fed groups had similar BMC, which was lower than that of the moderate-mineral group at 3 and 6 months of age. Adjusted mean BMC values for the moderate-mineral formula-fed group compared with the low-mineral formula- and human milk-fed groups were 127.8 +/- 1.5 (SEM) g vs 119. 2 +/- 1.5 and 122.1 +/- 1.4 g, respectively, at 3 months of age and 168.7 +/- 2.5 g vs 157.6 +/- 2.5 and 158.7 +/- 2.4 g, respectively, at 6 months of age. The BMC at 6 months of age among the formula-fed infants was correlated with both average dietary phosphorus intake (r = .592) and average daily calcium intake (r = .620) during the first 6 months. The relationships between BMC and these minerals remained significant even after controlling for caloric intake. It was not possible to determine the independent effects of dietary calcium and phosphorus on BMC because of the strong correlation of these minerals with each other. Despite significant differences in both calcium and phosphorus intakes during the second 6 months of life, there were no differences in growth parameters or bone mass accretion. Means for BMC, adjusted for body weight, length, and bone area, were not significantly different among feeding groups at either 9 or 12 months of age. Adjusted means were 199 +/- 2 (SEM) and 237 +/- 3 g at 9 and 12 months of age for infants receiving moderate-mineral formula; 198 +/- 2 and 236 +/- 3 g at 9 and 12 months of age for infants receiving the high-mineral formulas and 202 +/- 5 and 233 +/- 5 g at 9 and 12 months of age for infants receiving cow milk. The gain in bone mass during the second 6 months differed by the first 6-month feeding group; mean changes in BMC between 6 and 12 months, adjusted for changes in weight, length, and bone area, were greater in human milk-fed infants than in either the low- or moderate-mineral-containing formula groups: 81 +/- 16 g in human milk-fed infants and 73 +/- 15 and 71 +/- 15 g in the low- and moderate-mineral formula groups, respectively. Infants fed whole cow milk during the second 6 months were excluded from this analysis because of the small number of infants completing the study. By 12 months of age t


Antimicrobial prophylaxis in febrile neutropenia.
Antibiotics generally considered for antibacterial prophylaxis for immunosuppressed patients are trimethoprim-sulfamethoxazole and the quinolones. Trimethoprim-sulfamethoxazole can significantly reduce infections and is highly effective in preventing pneumonia due to Pneumocystis carinii. However, it can cause sulfonamide-related reactions, myelosuppression, oral candidiasis, and development of bacterial resistance, and it lacks activity against Pseudomonas aeruginosa. Quinolones can reduce the occurrence of fever and infections in patients with neutropenia but do not provide adequate coverage against gram-positive bacteria, and inappropriate use can induce resistance among gram-negative organisms. Routine antibacterial prophylaxis is not recommended for patients likely to develop neutropenia. Antifungal prophylaxis is appropriate in settings in which fungal infections are frequent. Fluconazole is recommended for patients who are to undergo hematopoietic stem cell transplantation; it can be considered for elderly patients with acute leukemia who are to receive intensive chemotherapy. Itraconazole can also be used. Prophylaxis with antiviral agents is generally not indicated; however, it should be given to hematopoietic stem cell transplant recipients.


Automated detection of genetic relatedness from fundus photographs using Siamese Neural Networks.
Heritability of common eye diseases and ocular traits are relatively high. Here, we develop an automated algorithm to detect genetic relatedness from color fundus photographs (FPs). We estimated the degree of shared ancestry amongst individuals in the UK Biobank using KING software. A convolutional Siamese neural network-based algorithm was trained to output a measure of genetic relatedness using 7224 pairs (3612 related and 3612 unrelated) of FPs. The model achieved high performance for prediction of genetic relatedness; when computed Euclidean distances were used to determine probability of relatedness, the area under the receiver operating characteristic curve (AUROC) for identifying related FPs reached 0.926. We performed external validation of our model using FPs from the LIFE-Adult study and achieved an AUROC of 0.69. An occlusion map indicates that the optic nerve and its surrounding area may be the most predictive of genetic relatedness. We demonstrate that genetic relatedness can be captured from FP features. This approach may be used to uncover novel biomarkers for common ocular diseases.


From biomass to a renewable LixC6O6 organic electrode for sustainable Li-ion batteries.
Li-ion batteries presently operate on inorganic insertion compounds. The abundance and materials life-cycle costs of such batteries may present issues in the long term with foreseeable large-scale applications. To address the issue of sustainability of electrode materials, a radically different approach from the conventional route has been adopted to develop new organic electrode materials. The oxocarbon salt Li2C6O6 is synthesized through potentially low-cost processes free of toxic solvents and by enlisting the use of natural organic sources (CO2-harvesting entities). It contains carbonyl groups as redox centres and can electrochemically react with four Li ions per formula unit. Such battery processing comes close to both sustainable and green chemistry concepts, which are not currently present in Li-ion cell technology. The consideration of renewable resources in designing electrode materials could potentially enable the realization of green and sustainable batteries within the next decade.


High Light-Induced Nitric Oxide Production Induces Autophagy and Cell Death in Chlamydomonas reinhardtii.
Autophagy plays a role in regulating important cellular functions in response to stress conditions. The role of nitric oxide (NO) in the regulation of autophagy in Chlamydomonas reinhardtii has been not studied. Illumination of C. reinhardtii cells under a high light (HL, 1,600 μmol m-2 s-1) condition induced a NO burst through NO synthase- and nitrate reductase-independent routes, and cell death. The abundance of CrATG8 protein, an autophagy marker of C. reinhardtii, increased after HL illumination along with a linear increase in the transcript abundance of autophagy-associated genes (CrVPS34, CrATG1, CrATG3, CrATG4, CrATG6, CrATG7, CrATG8, and CrATG12), which were suppressed in the presence of an NO scavenger, 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (cPTIO). The cells were treated with NO donors, S-nitroso-N-acetyl-penicillamine, and S-nitrosoglutathione, under a normal light (50 μmol m-2 s-1) condition to elucidate the role of NO in autophagy activation and cell death. Treatment with 0.05 mM or 0.1 mM NO donors increased the abundance of ATG8 protein and CrATG transcripts, which were suppressed in the presence of cPTIO. Moreover, treatment with 0.05 mM NO donors did not affect cell viability, while 0.1 mM NO donors elicited a transient decrease in cell growth and death that recovered after 12 h. The transient effect could be prevented by the presence of cPTIO. However, treatment with 1 mM H2O2 and 0.1 mM NO donors enhanced autophagy induction and resulted in cell death after 24 h. The interaction of H2O2 and NO can be prevented by cPTIO treatment. This implies that NO is critical for the interaction of H2O2 and NO that induces cell death and autophagy. Furthermore, exposure to 0.1 mM NO donors under a non-lethal HL condition (750 μmol m-2 s-1) evoked autophagy and cell death. In conclusion, the present findings demonstrated that the NO-mediated autophagy pathway is activated in C. reinhardtii under lethal high intensity illumination and may interact with H2O2 for HL-induced cell death. The relationships between autophagy and cell death are discussed.


Planning for biological disasters. Occupational health nurses as "first responders".
1. As a result of recent terrorist events, there is an immediate need for occupational nurses to review their disaster plans and to develop strategies to cope with bioterrorism in their workplaces. 2. The Centers for Disease Control and Prevention has identified three major categories of biological weapons. Category A, which is the highest priority category (and the focus of this article), includes smallpox, anthrax, botulism, plague, tularemia, filoviruses, and adenoviruses. Dealing with bioterrorism requires occupational health nurses to be familiar with these organisms, including their pathophysiology and methods of prevention, detection, and treatment. 3. Five principles can be used to guide responses to a biological attack. Incorporation of these principles into disaster planning will increase the effectiveness of responses to bioterrorism, if and when it occurs. Developing a plan of action before an event occurs will greatly enhance the likelihood that the repercussions of such an event are minimized.


Heterogeneity of the bovine adrenal steroid 21-hydroxylase.
The results presented indicate that purified cytochrome P-45021 which migrated upon SDS gel electrophoresis essentially as a single band, is further separable into different species by ion-exchange chromatography. The P-450 eluted from the CM-Sephadex column at different points along the buffer concentration gradient, exhibited significant differences in (1) the 21-hydroxylation of 17 alpha-OH-progesterone compared to progesterone and (2) the Type I spectral change produced by 17 alpha-OH-progesterone compared to that due to delta 4-androstenedione. These results indicate that the purified P-450 which appeared homogeneous contains different species differing in net charge and steroid preferences for 21-hydroxylation and binding. The ratio, 21-hydroxylation of 17 alpha-OH-progesterone/progesterone ranged between 2.6 and 0.86 suggesting that the purified preparation is a mixture of 17 alpha-OH-progesterone preferring and progesterone preferring species. Possible molecular bases for the heterogeneity of the 21-hydroxylase are discussed.


Complicated Native Aortic Valve Endocarditis: Complexities of Medical Optimisation Prior to Surgical Repair for Large Vegetations With Systemic Emboli.
A 43-year-old male with no history of valvular disease but ongoing intravenous drug use presented with acute confusion, pyrexia, and Osler's nodes. Transthoracic echocardiography uncovered a large 17 x 15 mm-sized vegetation on the aortic valve, causing moderate-to-severe aortic regurgitation. Subsequent multi-organ compromise and complexities regarding treatment adherence delayed surgical intervention; thus, six weeks of antibiotic therapy and medical optimisation, in close collaboration with cardiology, microbiology, and cardiothoracic teams, enabled definitive aortic valve repair to be performed. This case highlights the challenges encountered when managing this life-threatening condition and the obstacles of enacting the guidelines recommendations regarding the timing of surgical intervention. Our case portrays the effectiveness of medical management as bridge-to-surgery in patients not in a position to undergo immediate surgical repair.


Adverse events following immunization with oral poliovirus in Kinshasa, Democratic Republic of Congo: preliminary results.
We investigated the nature and frequency of adverse events following immunization (AEFI) associated with oral polio vaccines (OPV) in the general population in Kinshasa, Democratic Republic of Congo (DR Congo). The DR Congo National Pharmacovigilance Centre organized active AEFI surveillance during mass immunization campaigns for the general population from March to June 2011. A patient individual case safety report was used as a questionnaire and addressed to pupils and students from high schools and universities who had any adverse events after OPV administration. We used the preferred term from the WHO Adverse Reaction Terminology for AEFI designation. Here is presented the results of the second step of the mass immunization campaign. A total of 767 patients reported AEFI during the second step. Sex distribution shows that 512 (66·8%) students were females, while 255 (33·2%) were males, giving a female/male ratio 2∶1. The average age was 16·8±5·19 years (ranged: 6-35·5 years). Each person reported a mean of 1·33±0·6 AEFI. The average AEFI onset duration was 1·74±1·16 days post-vaccination, ranging from 1 to 9 days. Headache (22·4%), abdominal pain (17·2%), fever (11·7%), diarrhea (9·9%), and asthenia (7·5%) were the common symptoms. Paralysis and asthma-like reactions were rare and serious adverse events in this study. The most affected systems were gastro-intestinal (33·5%) and nervous system (29·3%). Rechallenge was positive for 173 persons (22·6%). OPV-related AEFIs are not uncommon, although it is under-reported. Active AEFI surveillance during mass immunization campaigns is very important and may help to detect rare and serious adverse events. Further investigation will be important to identify risk of AEFI with OPV in adults and is warranted to elucidate the cause of this association in the Congolese environment.


Combining laparoscopic and endovascular techniques to improve the outcome of aortic endografts. Hybrid techniques.
Aortic endografting can be performed with a high initial success rate yet with the need for lifelong surveillance because of numerous long term problems. Among these graft migration, typ II endoleaks and endotension require treatment to prevent abdominal aortic aneurysm (AAA) rupture. We describe our experience with laparoscopic clipping of lumbar arteries and the inferior mesenteric artery (IMA) to prevent Type II leaks as well as with different banding procedures. Several ways to perform active graft fixation are described. Since we believe that active downsizing of the aneurysm reduces some of the intermediate term problems we go a step further and evacuate the thrombus to downsize the aneurysm to prevent longitudinal shrinkage. Laparoscopic techniques can also be used to obtain direct vascular access. This permits insertion of a thoracic endograft directly into the aorta in patients with diseased iliac vessels. Endovascular aneurysm repair (EVAR) insertion under laparoscopic navigation without contrast dye in cases with renal insufficiency is described. We describe our technique of total laparoscopic conversion after failed endografting. Future perspectives and preliminary experience with an aortic stapler are discussed.


Descending thoracic aortic dissection: evaluation and management in the era of endovascular technology.
Acute aortic dissection is a relatively uncommon but highly lethal condition. Without proper treatment, devastating consequences can occur due to aortic rupture, cardiac tamponade, or irreversible ischemia involving the spinal cord or the visceral organs. The treatment strategy of this condition is in part influenced by the location and the severity of aortic dissection as immediate surgical intervention is necessary in acute ascending aortic dissection, whereas medical therapy is the initial treatment approach in uncomplicated descending aortic dissection. Recent advances of endovascular technology have broadened the potential application of this catheter-based therapy in aortic pathologies, including descending thoracic aortic dissection. In this article, the etiology, pathogenesis, and classification of this condition are discussed. The diagnostic benefits of various imaging modalities for descending aortic dissection are also discussed. Current treatment strategies, including medical, surgical, and catheter-based interventions, are reviewed. Lastly, clinical experiences of endovascular treatment for descending aortic dissection and various endovascular devices potentially applicable for this condition are discussed.


Fatal pneumonia caused by Burkholderia cepacia 9 months after resection of aspergilloma.
A 69-year-old man developed an episode of severe community-acquired pneumonia 9 months after resection of aspergilloma. Although Aspergillus fumigatus was also isolated in the pleural cavity, it did not invade the remaining lung parenchyma. The patient developed progressive bilateral pneumonia leading to death from respiratory failure. Burkholderia cepacia was considered as prime pathogen, as it was repeatedly cultured from sputum and tracheal secretions, as well as the autopsy lung. B. cepacia is resistant to most antibiotics, and seldom causes pneumonia in patients without cystic fibrosis or chronic granulomatous disease. The precise reason that this apparently immunocompetent patient developed B. cepacia pneumonia remains unknown.


Sensitivity, Specificity, Predictive Values, and Accuracy of Three Diagnostic Tests to Predict Inferior Alveolar Nerve Blockade Failure in Symptomatic Irreversible Pulpitis.
The inferior alveolar nerve block (IANB) is the most common anesthetic technique used on mandibular teeth during root canal treatment. Its success in the presence of preoperative inflammation is still controversial. The aim of this study was to evaluate the sensitivity, specificity, predictive values, and accuracy of three diagnostic tests used to predict IANB failure in symptomatic irreversible pulpitis (SIP). A cross-sectional study was carried out on the mandibular molars of 53 patients with SIP. All patients received a single cartridge of mepivacaine 2% with 1 : 100000 epinephrine using the IANB technique. Three diagnostic clinical tests were performed to detect anesthetic failure. Anesthetic failure was defined as a positive painful response to any of the three tests. Sensitivity, specificity, predictive values, accuracy, and ROC curves were calculated and compared and significant differences were analyzed. IANB failure was determined in 71.7% of the patients. The sensitivity scores for the three tests (lip numbness, the cold stimuli test, and responsiveness during endodontic access) were 0.03, 0.35, and 0.55, respectively, and the specificity score was determined as 1 for all of the tests. Clinically, none of the evaluated tests demonstrated a high enough accuracy (0.30, 0.53, and 0.68 for lip numbness, the cold stimuli test, and responsiveness during endodontic access, resp.). A comparison of the areas under the curve in the ROC analyses showed statistically significant differences between the three tests (p < 0.05). None of the analyzed tests demonstrated a high enough accuracy to be considered a reliable diagnostic tool for the prediction of anesthetic failure.


Expression of the type 1 and type 2 receptors for tumor necrosis factor after traumatic spinal cord injury in adult rats.
Posttraumatic inflammation has been implicated in secondary tissue damage after spinal cord injury (SCI). Tumor necrosis factor-alpha (TNF-alpha) is a key inflammatory mediator that is increasingly expressed after SCI. The effect of TNF-alpha is mediated through its receptors TNFR1 (p55) and TNFR2 (p75). However, whether these two receptors are expressed after SCI has not been demonstrated. In the present study, the temporo-spatial expression of TNFR1 and TNFR2 was examined in rats that had received a 10 g impact injury dropped at a height of 12.5 mm using the New York University impact device. In sham operates, no detectable TNFR1 or TNFR2 immunoreactivity (IR) was observed. In contused spinal cord, TNFR1 protein expression and immunoreactivity (IR) were detected as early as 15 min postinjury, reached its peak at 8 h, and declined markedly after 1 and 3 days postinjury. The temporal pattern of TNFR2 expression was similar to that of TNFR1 but its expression peaked at 4 h postinjury. During peak expression, TNFR1- and TNFR2-IR were most intense at the site of injury and decreased gradually from the injury epicenter. TNFR1- and TNFR2-positive cells included neurons, astrocytes, and oligodendrocytes. Methylprednisolone (MP), a synthetic glucocorticoid, partially inhibited the injury-induced expression of TNFR1 and TNFR2, an effect which could be reversed by RU486, an antagonist of glucocorticoid receptors. We suggest that the expression of TNFR1 and TNFR2 after SCI may contribute to posttraumatic inflammatory responses of TNF-alpha.


Exploring the detailed spatiotemporal characteristics of PM2.5: Generating a full-coverage and hourly PM2.5 dataset in the Sichuan Basin, China.
Fine particulate matter (PM2.5) has received worldwide attention due to its threat to public health. In the Sichuan Basin (SCB), PM2.5 is causing heavy health burdens due to its high concentrations and population density. Compared with other heavily polluted areas, less effort has been made to generate a full-coverage PM2.5 dataset of the SCB, in which the detailed PM2.5 spatiotemporal characteristics remain unclear. Considering commonly existing spatiotemporal autocorrelations, the top-of-atmosphere reflectance (TOAR) with a high coverage rate and other auxiliary data were employed to build commonly used random forest (RF) models to generate accurate hourly PM2.5 concentration predictions with a 0.05° × 0.05° spatial resolution in the SCB in 2016. Specifically, with historical concentrations predicted from a spatial RF (S-RF) and observed at stations, an alternative spatiotemporal RF (AST-RF) and spatiotemporal RF (ST-RF) were built in grids with stations (type 1). The predictions from the AST-RF in grids without stations (type 2) and observations in type 1 formed the PM2.5 dataset. The LOOCV R2, RMSE and MAE were 0.94/0.94, 8.71/8.62 μg∕m3 and 5.58/5.57 μg∕m3 in the AST-RF/ST-RF, respectively. Using the produced dataset, spatiotemporal analysis was conducted for a detailed understanding of the spatiotemporal characteristics of PM2.5 in the SCB. The PM2.5 concentrations gradually increased from the edge to the center of the SCB in spatial distribution. Two high-concentration areas centered on Chengdu and Zigong were observed throughout the year, while another high-concentration area centered on Dazhou was only observed in winter. The diurnal variation had double peaks and double valleys in the SCB. The concentrations were high at night and low in daytime, which suggests that characterizing the relationship between PM2.5 and adverse health outcomes by daily means might be inaccurate with most human activities conducted in daytime.


Comparison of different ionic liquids pretreatment for corn stover enzymatic saccharification.
Recently, application of ionic liquids (ILs) has received much attention due to their special solvency properties as a promising method of pretreatment for lignocellulosic biomass. Easy recovery of ionic liquids, chemical stability, temperature stability, nonflammability, low vapor pressure, and wide liquidus range are among those unique properties. These solvents are also known as green solvents due to their low vapor pressure. The present study was set to compare the effect of five different ILs, namely, 1-ethyl-3-methylimidazolium acetate ([EMIM][Ac]), 1-butyl-3-methylimidazolium chloride ([BMIM][Cl]), 1-ethyl-3-methyl imidazolium diethyl phosphate ([EMIM][DEP]), 1-allyl-3-methylimidazolium chloride ([AMIM][Cl]), and 1-ethyl-3-methylimidazolium-hydrogen sulfate ([EMIM][HSO₄]), on corn stover in a bioethanol production process. The performance of ILs was evaluated based on the change observed in chemical structure, crystallinity index, cellulose digestibility, and glucose release. Overall, [EMIM][Ac]-pretreated corn stover led to significantly higher saccharification, with cellulose digestibility reaching 69% after 72 hr, whereas digestibility of untreated barley straw was measured at only 21%.


Quantum diffusion wave-function approach to two-dimensional vibronic spectroscopy.
We apply the quantum diffusion wavefunction approach to calculate vibronic two-dimensional (2D) spectra. As an example, we use a system consisting of two electronic states with harmonic oscillator potentials which are coupled to a bath and interact with three time-delayed laser pulses. The first- and second-order perturbative wave functions which enter into the expression for the third-order polarization are determined for a sufficient number of stochastic runs. The wave-packet approach, besides being an alternative technique to calculate the spectra, offers an intuitive insight into the dissipation dynamics and its relation to the 2D vibronic spectra.


Intermolecular Dearomatization of Naphthalene Derivatives by Photoredox-Catalyzed 1,2-Hydroalkylation.
An intermolecular hydroalkylative dearomatization of naphthalenes with commercially available α-amino acids is achieved via visible-light photoredox catalysis. With an organic photocatalyst, a series of multi-substituted 1,2-dihydronaphthalenes are obtained in good-to-excellent yields. Intriguingly, by tuning the substituents at the C2 position of naphthalenes, formal dearomative [3+2] cycloadditions occur exclusively via a hydroalkylative dearomatization-cyclization sequence. This overall redox-neutral method features mild reaction conditions, good tolerance of functionalities, and operational simplicity. Diverse downstream elaborations of the products are demonstrated. Preliminary mechanistic studies suggest the involvement of a radical-radical coupling pathway.


[Rare causes of acute esophago-gastroduodenal hemorrhages].
Rare causes of acute esophagogastroduodenal hemorrhages were identified in 61 (4%) of 1,532 patients. Their number has increased 2.5-fold in the recent years due to the wide use of emergency endoscopy. Neoplastic diseases were encountered in 32, nonneoplastic diseases--in 29 patients. The source of the bleeding was in the esophagus in half of the cases, and emergency endoscopy was decisive in its identification. The greatest difficulties arise in the diagnosis of extragastric carcinoma complicated by bleeding. Active therapeutic tactics is advisable in nonepithelial tumors of the stomach complicated by hemorrhage, nonoperative treatment--in nonneoplastic diseases. Arrest of hemorrhage during endoscopy, by means of the polymer hemostatic ferracryl among other methods, increases the effect of nonoperative therapy. A fatal outcome occurred in 12 cases, 10 of them were with carcinoma of extragastric localization.


Protein-cofactor binding and ultrafast electron transfer in riboflavin binding protein under the spatial confinement of nanoscopic reverse micelles.
In this contribution, we study the effect of confinement on the ultrafast electron transfer (ET) dynamics of riboflavin binding protein (RBP) to the bound cofactor riboflavin (Rf, vitamin B2), an important metabolic process, in anionic sodium bis(2-ethylhexyl) sulfosuccinate reverse micelles (AOT-RMs) of various hydration levels. Notably, in addition to excluded volume effect, various nonspecific interactions like ionic charge of the confining surface can influence the biochemical reactions in the confined environment of the cell. To this end, we have also studied the ET dynamics of RBP-Rf complex under the confinement of a cationic hexadecyltrimethylammonium bromide (CTAB) RMs with similar water pool size to the anionic AOT-RMs towards simulating equal restricted volume effect. It has been found that the spatial confinement of RBP in the AOT-RM of w(0) = 10 leads to the loss of its tertiary structure and hence vitamin binding capacity. Although, RBP regains its binding capacity and tertiary structure in AOT-RMs of w(0) ≥ 20 due to its complete hydration, the ultrafast ET from RBP to Rf merely occurs in such systems. However, to our surprise, the ET process is found to occur in cationic CTAB-RMs of similar volume restriction. It is found that under the spatial confinement of anionic AOT-RM, the isoalloxazine ring of Rf is improperly placed in the protein nanospace so that ET between RBP and Rf is not permitted. This anomaly in the binding behaviour of Rf to RBP in AOT-RMs is believed to be the influence of repulsive potential of the anionic AOT-RM surface to the protein. Our finding thus suggests that under similar size restriction, both the hydration and surface charge of the confining volume could have major implication in the intraprotein ET dynamics in real cellular environments.


Localization of optically excited states by self-trapping.
We discuss the localization of the surface exciton at the Si(111)- (2x1) surface due to self-trapping, which leads to a characteristic temperature-dependent linewidth of the optical response and to a significant Stokes shift of the luminescence. Self-trapping results in this case from a structural relaxation in the excited state, caused by the interplay between electronic and geometric degrees of freedom. The most significant contribution to this effect comes from one single geometric deformation mode which is driven by the internal electronic charge transfer in the self-trapped exciton.