Tryptanthrin content in Isatis tinctoria leaves--a comparative study of selected strains and post-harvest treatments.
Tryptanthrin is a pharmacologically active compound in the anti-inflammatory herb Isatis tinctoria, with potent inhibitory activity on prostaglandin and leukotriene synthesis and on inducible NO synthase. The tryptanthrin content of five defined woad strains was analyzed in dependence of the time of harvest and post-harvest treatment. Tryptanthrin was determined by a validated ESI-LC-MS isotope dilution assay with d(8)-tryptanthrin as internal standard. The tryptanthrin concentration in freeze-dried leaf samples was low. Drying at ambient temperature led to a significant increase of tryptanthrin concentration, but the highest concentrations were found when leaves were dried at 40 degrees C. Tryptanthrin content in fermented woad leaves was below the limit of quantification. Tryptanthrin appears thus to be a product of post-harvest processes, but details of its formation remain to be elucidated.


[Bronchial hyperreactivity: pathomechanisms, diagnosis and perspectives of therapy].
Bronchial asthma is a problem with increasing importance for health care. Bronchial hyperreactivity can be considered as the precondition of the development of bronchial asthma. The biological and pathophysiological activities of the phospholipid mediators discovered during the last years induced considerable progress in the research of pathogenesis in bronchial asthma. Thus, a central role of leucotrienes, HPETE and PAF in regulation of bronchomotoric actions is suggested. From recent epidemiologic and clinical research certain risk factors of manifestation of bronchial asthma can be derived. At present, theoretical, completely new therapeutical concepts are directed on inhibition of synthesis or receptor antagonism in different levels of the phospholipid metabolism.


Usefulness of aliasing phenomenon for diagnosing venous valve stenosis of arteriovenous fistula in a hemodialysis patient.
We present venous valve stenosis, which is an uncommon cause of arteriovenous fistula (AVF) dysfunction. Owing to the thin structure in echography, venous valves are challenging to observe; however, we have found that the aliasing phenomenon is useful for diagnosing venous valve stenosis.


Predicting herbicides concentrations in paddy water and runoff to the river basin.
This study was conducted to investigate the dissipation pattern and runoff of herbicides to the river basin from the paddy fields. Pesticide paddy field model (PADDY) was applied to predict herbicide concentration in paddy fields. A field study was conducted in a paddy farm of Higashi Hiroshima City, Hiroshima Prefecture, Japan in the year of 2003 paddy season. The herbicides were mefenacet, thiobencarb, and bensulfuron methyl. The sample water was analyzed by using gas chromatography and HPLC after solid phase extraction. Predicted dissipation rate of thiobencarb in paddy water was higher (DT50 = 4.36) than that measured, with a lower k value (-0.069). Two weeks after application no thiobencarb was detected in the drainage channel and down stream. In the down stream, thiobencarb was detected until 3 d after application, with a range of 0.02% to 0.08% of applied herbicide. The predicted dissipation rate (k) and half-life (DT50) of mefenacet was not significantly different from that of measured. In the drainage channel, upstream and downstream mefenacet was found during the whole study period. In downstream, the maximum concentration of mefenacet was present 0.61% of applied in the paddy field on 3DAH. The dissipation rate (k) of BSM varied from -0.0860 to -0.1059 to with half-life (DT50) 3.5 and 2.84 d. In upstream water, no BSM was detected except trace amounts (0.01 microg/L) at 3 d after application. However, in the drainage channel 8%, 6% and 1.58% of applied BSM was present at 0, 1 and 3 d after application respectively. In the down stream, the highest concentration was 1.06%, shortly after application.


Subjective and objective findings in patients with true dehiscence versus thin bone over the superior semicircular canal.
To compare subjective and objective findings between patients with true dehiscence versus thin bone over the superior semicircular canal (SSC). Retrospective case series. Tertiary referral center. All patients from our institution with true dehiscence or thin bone over the SSC on computed tomography temporal bone (oblique view) from 2007 to 2013. Subjective test: Dizziness Handicap Inventory (DHI). Objective tests: Infrared video eye recording with varying stimuli (Tulio, Fistula, and Vibration); vestibular evoked myogenic potential (VEMP); electrocochleography; videonystagmography; pure-tone audiometry (i.e., air-bone gap). Fifty-four patients (64 ears) were reviewed. Thirty-nine patients (47 ears) had true dehiscence of the SSC on temporal bone computed tomography. Fifteen patients (17 ears) had thin bone over the SSC. There was no statistical difference in DHI scores for patients with true dehiscence versus those with thin bone over the SSC. Only cervical VEMP and air-bone gap via pure-tone audiometry revealed a significant difference between the two groups. The remaining vestibular assessments did not demonstrate any difference. No significant correlations were revealed between DHI and objective test findings across and within the two groups. Among the objective tests, cervical VEMP and pure-tone audiometry are the only tools to distinguish between true dehiscence and thin bone over the SSC. DHI does not differentiate between these two groups. Furthermore, no correlation exists between DHI and any objective finding. Further investigation is necessary to develop a validated subjective symptom index of patients with SSC syndrome.


All-atom normal-mode analysis reveals an RNA-induced allostery in a bacteriophage coat protein.
Assembly of the T=3 bacteriophage MS2 is initiated by the binding of a 19 nucleotide RNA stem loop from within the phage genome to a symmetric coat protein dimer. This binding event effects a folding of the FG loop in one of the protein subunits of the dimer and results in the formation of an asymmetric dimer. Since both the symmetric and asymmetric forms of the dimer are needed for the assembly of the protein container, this allosteric switch plays an important role in the life cycle of the phage. We provide here details of an all-atom normal-mode analysis of this allosteric effect. The results suggest that asymmetric contacts between the A -duplex RNA phosphodiester backbone of the stem loop with the EF loop in one coat protein subunit results in an increased dynamic behavior of its FG loop. The four lowest-frequency modes, which encompass motions predominantly on the FG loops, account for over 90% of the increased dynamic behavior due to a localization of the vibrational pattern on a single FG loop. Finally, we show that an analysis of the allosteric effect using an elastic network model fails to predict this localization effect, highlighting the importance of using an all-atom full force field method for this problem.


Examining the relationship between autistic traits and college adjustment.
We examined the relationship between characteristics associated with autism spectrum disorder and college adjustment in a sample of neurotypical college students. Using the Broad Autism Phenotype Questionnaire and the Student Adaptation to College Questionnaire, we found that higher levels of autism spectrum disorder characteristics were associated with poorer adjustment to college. One subscale of the Broad Autism Phenotype Questionnaire, pragmatic language difficulties, explained the most variance in adjustment. In addition, students who met the previously established cut-off scores for possessing the broad autism phenotype scored significantly lower on all Student Adaptation to College Questionnaire subscales. Finally, pragmatic language difficulties mediated the relationship between college major and academic adjustment. These findings underscore the need for future research to examine how pragmatic language difficulties may impede college success in students with autism spectrum disorder and in the typical population.


Regulation of Na,K-ATPase activity.
The sodium pump Na,K-ATPase, a heterodimer of an alpha catalytic subunit and a beta glycoprotein subunit, is regulated by a wide array of hormonal, autocrine, and paracrine factors. Both short-term acute adjustments of activity and long-term adjustments of sodium pump pool size are important determinants of cellular Na,K-ATPase activity. Phosphorylation and dephosphorylation are implicated in the acute regulation of activity. Although there is not yet any direct demonstration of phosphorylation in vivo, in vitro studies on purified enzyme directly demonstrate that phosphorylation decreases Na,K-ATPase activity. In addition, it is likely that phosphorylation of other proteins regulates sodium pump activity and cellular distribution. In regard to long-term regulation, recent demonstration of differential translatability of alpha and beta mRNAs and differential stability of newly synthesized alpha and beta subunits suggests that beta subunit is synthesized in excess over alpha subunit and that the excess is rapidly degraded. The isoform composition of alpha beta heterodimers has been shown to affect enzymatic properties, and tissue-specific heterodimer patterns are emerging from regulation studies. In regard to Na,K-ATPase and hypertension, there is continued interest in the significance of the uncoupling of dopamine inhibition of proximal tubule Na,K-ATPase activity in hypertensive rat strains. The uncoupling has been shown to be specific to the proximal tubule, which has been shown to express DA1 dopamine receptors, and both receptor and postreceptor defects are implicated. Questions remaining include how activation of dopamine receptors is coupled to decreased sodium transporter expression in the proximal tubule (short- and long-term regulation) in normotensive rats, the precise nature of the defect in hypertension, and whether a similar defect is observed in human hypertensive patients.


Work participation in adults with Marfan syndrome: Demographic characteristics, MFS related health symptoms, chronic pain, and fatigue.
Marfan syndrome (MFS) is a severe autosomal dominant connective tissue disorder that might influence peoples work ability. This cross sectional study aims to investigate work participation in adults with verified MFS diagnosis and to explore how the health related consequences of MFS and other factors might influence work participation. The prevalence of health problems in young adults compared to older adults with MFS was examined in association to work participation. A postal questionnaire including questions about work participation, demographic characteristics, MFS related health problems, chronic pain, and fatigue was sent to 117 adults with verified MFS (Ghent 1), and 62% answered. Fifty-nine percent were employed or students, significantly lower work participation than the General Norwegian Population (GNP), but higher than the Norwegian population of people with disability. Most young adults worked full-time despite extensive health problems, but the average age for leaving work was low. Few had received any work adaptations prior to retiring from work. In multiple logistic regression analysis, only age, lower educational level and severe fatigue were significantly associated with low work participation; not MFS related health problems or chronic pain. Fatigue appears to be the most challenging health problem to deal with in work, but the covariance is complex. Focus on vocational guidance early in life, more appropriate work adaptations, and psychosocial support might improve the possibility for sustaining in work for adults with MFS. More research about work challenges in adults with MFS is needed.


Stucco keratoses. A clinico-pathological study.
Stucco keratoses are benign acquired papular warty lesions which usually occur on the distal parts of the lower limbs of elderly men. Their nature and pathogenesis are uncertain. Eight patients with multiple stucco keratoses who presented to the Cardiff Dermatology Department over an 18-month period were studied in an attempt to characterize these lesions. All subjects were male, with ages ranging from 50 to 72 years. Their lesions were most numerous over the fronts of the lower legs, but were also evident over other areas of the limbs. Most patients had a history of prolonged solar exposure, but the relationship of this to the development of the lesions was uncertain. Histologically there were no dysplastic changes and a characteristic regular 'church spire' type retention hyperkeratosis without marked acanthosis was evident. Lack of a marked increase in the epidermal cell population size is reflected in the normal in vitro tritiated thymidine autoradiographic labelling indices (7.81 +/- 1.67%, normal range 5 to 9%). Ultrastructurally no viral particles were evident and a normal pattern of epidermal differentiation with hypergranulosis was present. Two of the patients with myriads of lesions who were treated for 2 months with etretinate showed a dramatic clinical improvement which, however, lasted for 6 months only.


A Preliminary Look at the Macrovascular System for Transmetatarsal Amputation Success.
Transmetatarsal amputation (TMA) is a commonly used level of amputation that preserves most of the foot's function and independence. However, many TMAs fail, and patients go onto higher amputations. The primary endpoint of this study is to determine if source artery occlusions are correlated with TMA flap failure. A total of 82 patients with TMAs were retrospectively reviewed for healing rates between 2009 and 2019 at a single center. Forty-five of the patients had an angiogram, which was analyzed for source artery and overall TMA failure. Of the initial 82 patients, a cohort of 12 had documentation of specific flap failure and an angiogram performed. This cohort of 12 patients was used for correlation of flap failure with source artery occlusion. Overall, the TMA healing rate was 45.28%. No correlation was noted between a specific source artery occlusion and overall TMA failure. However, a moderate positive correlation was seen with dorsalis pedis artery and peroneal artery occlusions and dorsal flap failure. No correlation was seen with the posterior tibial artery and plantar flap failure. A moderate negative correlation was seen with peroneal artery occlusion and plantar flap failure. The authors concluded that retrograde flow through the angiosome principle is what allowed for successful outcomes in TMAs. Physicians are urged to carefully plan, dissect, and preserve these vessels to help prevent TMA flap failure, especially in patients with vascular risk or disease.


Fabrication and evaluation of valsartan-polymer- surfactant composite nanoparticles by using the supercritical antisolvent process.
The aim of this study was to fabricate valsartan composite nanoparticles by using the supercritical antisolvent (SAS) process, and to evaluate the correlation between in vitro dissolution and in vivo pharmacokinetic parameters for the poorly water-soluble drug valsartan. Spherical composite nanoparticles with a mean size smaller than 400 nm, which contained valsartan, were successfully fabricated by using the SAS process. X-ray diffraction and thermal analyses indicated that valsartan was present in an amorphous form within the composite nanoparticles. The in vitro dissolution and oral bioavailability of valsartan were dramatically enhanced by the composite nanoparticles. Valsartan-hydroxypropyl methylcellulose-poloxamer 407 nanoparticles exhibited faster drug release (up to 90% within 10 minutes under all dissolution conditions) and higher oral bioavailability than the raw material, with an approximately 7.2-fold higher maximum plasma concentration. In addition, there was a positive linear correlation between the pharmacokinetic parameters and the in vitro dissolution efficiency. Therefore, the preparation of composite nanoparticles with valsartan-hydroxypropyl methylcellulose and poloxamer 407 by using the SAS process could be an effective formulation strategy for the development of a new dosage form of valsartan with high oral bioavailability.


Bone edema determined by magnetic resonance imaging reflects severe disease status in patients with early-stage rheumatoid arthritis.
To determine the significance of bone edema, detected by magnetic resonance imaging (MRI), in early-stage rheumatoid arthritis (RA). We simultaneously examined serologic variables, MRI of wrist sites and finger joints of both hands, clinical disease activity score (DAS), and HLA-DR typing at entry in 80 patients with early-stage RA. The number of bones scored as positive for bone edema correlated with the number of sites scored as positive for MRI synovitis and MRI bone erosion, rate of enhancement (E-rate), and serum C-reactive protein (CRP), matrix metalloproteinase 3 (MMP-3), and interleukin 6 (IL-6). Findings for MRI synovitis and MRI bone erosion, E-rate, CRP, MMP-3, IL-6, seropositivity, and titer of anti-cyclic citrullinated peptide antibody (anti-CCP antibody), DAS28-CRP and HLA-DRB1*0405 allele carriership, were significantly higher in the positive versus the negative bone edema group. Bone edema based on our scoring system may reflect severe disease status in patients with early-stage RA. However, its clinical value at entry in prognostication of RA should be examined through prospective clinical followup studies.


Reliably picking the best endpoint.
Endpoint selection in clinical trials involves a variety of considerations. One important consideration is the sample size required to power a future clinical trial. In this work, we define the sample size ratio, θ, as the ratio of sample sizes required to power a future trial. We consider in detail the setting of continuous endpoints where a Welch's t-statistic is used to analyze the data. We develop an estimator that depends on the squared ratio of estimated standardized treatment effects, and the quadrant on the plane in which they fall. We evaluate bootstrap and profile likelihood methods for construction of confidence intervals. Generalizations to other endpoints and testing of nonnested models are discussed. The methods are applied to analyze two different assays that measure antibody abundance using data from an Ebola vaccine field trial.


Serum calcium as a biomarker of clinical severity and prognosis in patients with coronavirus disease 2019.
The aim of this study was to investigate the correlations between serum calcium and clinical outcomes in patients with coronavirus disease 2019 (COVID-19). In this retrospective study, serum calcium levels, hormone levels and clinical laboratory parameters on admission were recorded. The clinical outcome variables were also recorded. From February 10 to February 28, 2020, 241 patients were enrolled. Of these patients, 180 (74.7%) had hypocalcemia on admission. The median serum calcium levels were 2.12 (IQR, 2.04-2.20) mmol/L, median parathyroid hormone (PTH) levels were 55.27 (IQR, 42.73-73.15) pg/mL, and median 25-hydroxy-vitamin D (VD) levels were 10.20 (IQR, 8.20-12.65) ng/mL. The serum calcium levels were significantly positively correlated with VD levels (P =0.004) but negatively correlated with PTH levels (P =0.048). Patients with lower serum calcium levels (especially ≤2.0 mmol/L) had worse clinical parameters, higher incidences of organ injury and septic shock, and higher 28-day mortality. The areas under the receiver operating characteristic curves of multiple organ dysfunction syndrome, septic shock, and 28-day mortality were 0.923 (P <0.001), 0.905 (P =0.001), and 0.929 (P <0.001), respectively. In conclusion, serum calcium was associated with the clinical severity and prognosis of patients with COVID-19. Hypocalcemia may be associated with imbalanced VD and PTH levels.


Internet use, social engagement and health literacy decline during ageing in a longitudinal cohort of older English adults.
Health literacy skills tend to decline during ageing, which is often attributed to age-related cognitive decline. Whether health literacy skills may be influenced by technological and social factors during ageing is unknown. We investigated whether internet use and social engagement protect against health literacy decline during ageing, independent of cognitive decline. We used prospective data from 4368 men and women aged ≥52 years in the English Longitudinal Study of Ageing from 2004 to 2011. Health literacy was measured at baseline (2004-2005) and at follow-up (2010-2011) using a reading comprehension test of a fictitious medicine label. The influences of consistent internet use and engagement in each of the civic, leisure and cultural activities on health literacy decline over the follow-up were estimated. After adjusting for cognitive decline and other covariates, consistent internet use (1379/4368; 32%) was protectively associated with health literacy decline (OR=0.77; 95% CI 0.60 to 0.99), as was consistent engagement in cultural activities (1715/4368; 39%; OR=0.73; 95% CI 0.56 to 0.93). As the number of activities engaged in increased, the likelihood of health literacy decline steadily decreased (ptrend<0.0001), with OR=0.51 (95% CI 0.33 to 0.79) for engaging in all four of the internet use and civic, leisure and cultural activities versus none. Internet use and social engagement, particularly in cultural activities (eg, attending the cinema, art galleries, museums and the theatre), may help older adults to maintain health literacy during ageing. Support for older adults to maintain socially engaged lives and to access the internet should help promote the maintenance of functional literacy skills during ageing.


High salt culture conditions inhibit serum- and NGF- but not PMA-induced Egr-1 gene transcription in rat C6 glioma cells.
Recent studies have suggested that glial cells may play a physiologically important role in the retention and restoration of neuronal cell integrity, proposing the possibility that the proliferation and/or differentiation of glial cells may be related to pathological changes in neural functions in neurodegenerative diseases, and hence, it seems interesting to investigate the expression of genes related to the proliferation and differentiation of glial cells. Following this basic concept, we have previously examined the influence of culture conditions on egr-1 gene expression in rat C6 glioma cells and have shown that brief exposure of these cells to high salt culture medium can induce the down-regulation of egr-1 gene expression. In contrast, the long-term culture of these cells in high salt medium has been shown to primarily reduce their proliferation and secondarily elevate egr-1 gene transcription as a consequence of arresting the cell-cycle progression. Therefore, the effect of high salt culture medium on egr-1 gene expression seems practically unconfirmed, and remains to be further investigated. Then, the effects of various egr-1 gene inducers, such as serum, NGF and phorbol ester PMA, on Egr-1 mRNA levels in the glioma cells were examined under the high salt culture conditions. The brief exposure to high salt culture medium inhibited the elevation of Egr-1 mRNA levels induced by serum replenishment and NGF, but not induced by PMA. These results suggest that the suppression of serum action on egr-1 gene transcription may be the primary and essential event leading to the down-regulation of egr-1 gene expression under the high salt culture conditions.


Unravelling the binding affinity between model transport protein and a prospective tuberculosis therapeutic agent: a spectroscopic and theoretical simulation exploration.
Haloxyfop was reported to exhibit inhibition effect targeting Mycobacterium tuberculosis and pathogenic parasites. To pave its way for drug development, more research is required to determine the affinities interacting with biological receptors in vivo. In this work, the interactions of Haloxyfop with two model transport proteins were investigated by spectroscopic techniques and theoretical simulation. The interaction mechanism, thermodynamic properties and the impact of Haloxyfop-induced conformational change in serum albumins were revealed by series of fluorescence, UV-Vis absorption and circular dichroic spectroscopy. The specific binding sites were determined by site-competitive replacement experiment. Molecular docking and dynamic simulation provided a visual screening in the microscopic binding mode. The structure of Haloxyfop was roughly divided into three parts that exhibit different covalent interaction affinities. The two isomers of Haloxyfop showed a certain degree of affinity difference. Hydrophobic, polar interaction and π-effect were analyzed in detail, and the surface electrostatic potential energy maps were simulated to provide references. The free energy, calculated by the molecular mechanics-generalized born surface area (MM-GBSA) and molecular mechanics-Poisson Boltzmann surface area (MM-PBSA) methods, was decomposed to per-residues, which intuitively revealed relevant contributions in binding process. The role of water existence was explored through molecular dynamic refinement, and the frontier molecular orbital analysis explored the ionic interaction mechanism in electronic level. In general, multiple chemistry method was adopted to fully unravel the properties of Haloxyfop-binding for the sake of rationalizing the applicability as a therapeutic agent. Communicated by Ramaswamy H. Sarma.


Using interpreters - a guide for GPs.
Australia is one of the most multilingual countries in the world. In their working lives, all doctors will need to communicate with patients whose languages they do not speak. To outline Australia's system for providing interpreters for medical consultations, and to discuss optimal ways of working with these interpreters. Australia has the world's largest free telephone interpreter service for doctors. All general practitioners claiming Medicare consultations can contact this service, quote a doctor code or Medicare provider number, and generally receive an interpreter within 3 minutes. Onsite interpreters can be booked if required. State and territory health services can also provide onsite and telephone interpreters. Despite this, interpreters are underused in Australia. Practices can improve their uptake of interpreters by establishing routine systems to contact interpreters when needed; however nation wide measures are also needed, including education and providing incentives through the Medicare fee structure. Decisions about when to contact an interpreter will be determined by patient or doctor request, the nature of the illness, and/or the subject of the consultation. The quality of interpreted consultations can be improved if the GP speaks slowly and speaks to the patient, not the interpreter; allows time for the interpreter to interpret the elements of the consultation to the patient; and remains in charge of the consultation. Information in many languages is now widely available on the internet, and can be a useful supplement to the interpreted consultation.


The formate dehydrogenase enhances aluminum tolerance of tobacco.
The formate dehydrogenase (FDH) is regarded as a universal stress protein involved in various plant abiotic stress responses. This study aims to ascertain GmFDH function in conferring tolerance to aluminum (Al) stress. The bioinformatics analysis demonstrates that GmFDH from Tamba black soybean (TBS) encodes FDH. Quantitative reverse transcription-PCR (qRT-PCR) showed that GmFDH expression was induced by Al stress with a concentration-time-specific pattern. Moreover, Al stress promotes formate content and activates FDH activity. Further studies revealed that GmFDH overexpression alleviated root growth of tobacco under Al stress inhibition and reduced Al and ROS accumulation in roots. In addition, transgenic tobacco had much more root citrate exudation and much higher activity of antioxidant enzymes than wild type. Moreover, under Al stress, NtMATE and NtALS3 expression showed no changes in wild type and overexpression lines, suggesting that here the known Al-resistant mechanisms are not involved. However citrate synthase activity is higher in transgenic tobaccos than that of wild type, which might be the reason for citrate secretion increase. Thus, the increased Al tolerance of GmFDH overexpression lines is likely attributable to enhanced activities of antioxidant enzymes and promoting citrate secretion. Taken together, our findings advance understanding of higher plant Al toxicity mechanisms and suggest a possible new route towards the improvement of plant growth under Al stress.


Primary adenocarcinoma of the rete testis: A case report and review of the literature.
Primary adenocarcinoma of the rete testis is an extremely rare extratesticular neoplasm. Due to its low occurrence and the scarcity of data, sonographic characteristics of adenocarcinoma of the rete testis are still poorly defined. A 46-year-old male complained of swelling and pain in the right side of the scrotum. No associated symptoms were observed. Anti-tuberculosis chemotherapy yielded no response. Postoperative pathology revealed a diagnosis of poorly-differentiated adenocarcinoma of the rete testis. Using the ultrasonography features observed, combined with a review of current literature, the diagnosis and differential diagnosis of this neoplasm are presented.


The colonic mucosa-associated microbiome in SIV infection: shift towards Bacteroidetes coincides with mucosal CD4+ T cell depletion and enterocyte damage.
The intesinal microbiome is considered important in human immunodeficiency virus (HIV) pathogenesis and therefore represents a potential therapeutic target to improve the patients' health status. Longitudinal alterations in the colonic mucosa-associated microbiome during simian immunodeficiency virus (SIV) infection were investigated using a 16S rRNA amplicon approach on the Illumina sequencing platform and bioinformatics analyses. Following SIV infection of six animals, no alterations in microbial composition were observed before the viral load peaked in the colon. At the time of acute mucosal SIV replication, the phylum Bacteroidetes including the Bacteroidia class as well as the phylum Firmicutes and its families Ruminococcaceae and Eubacteriaceae became more abundant. Enrichment of Bacteroidetes was maintained until the chronic phase of SIV infection. The shift towards Bacteroidetes in the mucosa-associated microbiome was associated with the extent of SIV infection-induced mucosal CD4+ T cell depletion and correlated with increasing rates of enterocyte damage. These observations suggest that Bacteroidetes strains increase during virus-induced mucosal immune destruction. As Bacteroidetes belong to the lipopolysaccharide- and short chain fatty acids-producing bacteria, their rapid enrichment may contribute to inflammatory tissue damage and metabolic alterations in SIV/HIV infection. These aspects should be considered in future studies on therapeutic interventions.


Evaluating the outcome of vocational rehabilitation.
This paper presents an analysis of studies in which vocational rehabilitation was followed up during the 1980s and early 1990s. Its purpose is to clarify the outcome of vocational rehabilitation as well as the factors predicting that outcome. In these follow-up studies the variables by which the outcome is measured are closely linked with the subjects' employment opportunities, and are basically the same as those applied in earlier follow-up studies. Because of the study designs it is difficult to make any generalizations concerning the results. Little attention has been paid to the evaluation of psychological adaptation in most of these studies. Also, follow-up studies generally have not taken into account the employment situation. Whether those who have had rehabilitation are able to find employment depends essentially on employers' policies towards the handicapped and the disabled.


Multiple antenatal bookings among pregnant women in Enugu, Nigeria.
Some pregnant women do book concurrently with multiple antenatal care providers. Structured questionnaires were administered to women attending antenatal clinics in 12 facilities in Enugu, Nigeria. A total of 535 women responded: 372 (69.5%) were booked into more than one facility and 163 (30.5%) were booked into a single facility; 280 (52.3%) booked into the two Teaching Hospitals and 91 (12.5%) booked with a traditional birth attendant. Reasons for multiple bookings included selecting a facility with affordable prices (43.9%); selecting a facility promising vaginal delivery (35.3%); avoiding HIV testing (17.9%); avoiding caesarean section (10.8%); avoiding being regarded as unbooked (10.1%) and booking into a facility where they were not known. Possible disadvantages were confusion in deciding where to deliver (53.1%); default on expert advice (27.5%); mismanagement (18.7%); delays, complications and death (12.5%). Multiple bookings were common in this study. Disadvantages of this practice, including risk of death, were identified by the women.


[Non bullous impetigo: streptococcal or staphylococcal?].
Non bullous impetigo is very common among the pediatric population. It is caused by bacteria. For twenty years, Staphylococcus aureus has been the most frequently isolated organism (present in 80 % of non bullous impetigo lesions, it is the only pathogen cultured in 50 % of patients). The group A beta-haemolytic streptococcus is at the moment isolated alone in 3% of lesions and in association with S. Aureus in 30 % of patients. An epidemiologic change seems to have occurred. Until the early 1980s, group A beta-haemolytic streptococcus was indeed the most predominant etiologic agent causing non bullous impetigo. Unfortunately, the rate of resistance among staphylococci responsible of non bullous impetigo is increasing. As serious complications can follow this skin infection, an appropriate treatment is necessary combining local care, topical antibiotics and sometimes adjunction of systemic antibiotics.


Analysis of physiological signals using state space correlation entropy.
In this letter, the authors propose a new entropy measure for analysis of time series. This measure is termed as the state space correlation entropy (SSCE). The state space reconstruction is used to evaluate the embedding vectors of a time series. The SSCE is computed from the probability of the correlations of the embedding vectors. The performance of SSCE measure is evaluated using both synthetic and real valued signals. The experimental results reveal that, the proposed SSCE measure along with SVM classifier have sensitivity value of 91.60%, which is higher than the performance of both sample entropy and permutation entropy features for detection of shockable ventricular arrhythmia.


Modulation of cortical activation and behavioral arousal by cholinergic and orexinergic systems.
Multiple neuronal systems contribute to the promotion and maintenance of the wake state, which is characterized by cortical activation and behavioral arousal. Using predominantly glutamate as a neurotransmitter, neurons within the reticular formation of the brainstem give rise to either ascending projections into the forebrain or descending projections into the spinal cord to promote through relays fast cortical activity or motor activity with postural muscle tone. Using acetylcholine, cholinergic neurons in the brainstem project to forebrain relays and others in the basal forebrain to the cortex, by which they stimulate fast gamma activity during waking and during rapid eye movement or paradoxical sleep (PS). Other neuromodulatory systems, such as noradrenergic locus coeruleus neurons, give rise to highly diffuse projections through brain and spinal cord and simultaneously stimulate cortical activation and behavioral arousal. Although such neuromodulatory systems were thought to be redundant, a recently discovered peptide called orexin (Orx) or hypocretin, contained in diffusely projecting neurons of the hypothalamus, was found to be essential for the maintenance of waking with muscle tone, since in its absence narcolepsy with cataplexy occurred. Orx neurons discharge during active waking and cease firing during sleep. Since cholinergic neurons discharge during waking and PS, they would stimulate cortical activation in association with muscle tone when orexinergic neurons are also active but would stimulate cortical activation with muscle atonia when orexinergic neurons are silent, as in natural PS, or absent, as in pathological narcolepsy with cataplexy.


Hypokalaemic metabolic alkalosis, hypertension and diabetes: what is the link.
Two years after diagnosis of a metastatic neuroendocrine gastrin-secreting tumour and after several cycles of chemotherapy and peptide receptor radionuclide therapy, a 56-year-old woman presented with hypokalaemic metabolic alkalosis, hypertension, leg oedema and new-onset diabetes mellitus. Further investigations revealed renal potassium loss confirmed by a transtubular potassium gradient of 16, fully suppressed serum aldosterone, but instead highly elevated blood levels of morning cortisol and adrenocorticotropic hormone as well as increased urinary excretion of glucocorticoid and mineralocorticoid metabolites. Ruling out other causes, paraneoplastic hypercortisolism was diagnosed. Pharmacological inhibition of the steroid 11β-hydroxylase with metyrapone resulted in complete resolution of metabolic alkalosis, hypokalaemia, hypertension, hyperglycaemia and leg oedema within 1 week.


[Suitability evaluation of Panax quinquefolium's producing area based on TCMGIS- I].
To supply the scientific data for the choice of medicinal plants' producing area through analyzing the suitable area for Panax quinquefolium' growth. TCMGIS-I (Suitability evaluation geographic information system of traditional Chinese medicine producing area) was developed and used to analyze the suitable producing area of P. quinquefolium Wisconsin state of USA, one of the origin producing area of the geo-authentic crude drugs, was selected as the standard analytical area and some key factors related to plant growth such as average temperature, altitude, soil type, precipitation were chosen to be considered. The result showed that the suitable area for P. quinquefolium' growth in China is similar to the present status. It concentrates in the northeast and the north of China, and part of Shanxi province is also suitable but the field area is small. The development of P. quinquefolium in China should concentrate in the northeast and the north of China. The TCMGIS-I is valuable to the analysis of suitable producing area and introduction of medicinal plant.


Lower levels of uric acid and striatal dopamine in non-tremor dominant Parkinson's disease subtype.
Parkinson's disease (PD) patients who present with tremor and maintain a predominance of tremor have a better prognosis. Similarly, PD patients with high levels of uric acid (UA), a natural neuroprotectant, have also a better disease course. Our aim was to investigate whether PD motor subtypes differ in their levels of UA, and if these differences correlate with the degree of dopamine transporter (DAT) availability. We included 75 PD patients from whom we collected information about their motor symptoms, DAT imaging and UA concentration levels. Based on the predominance of their motor symptoms, patients were classified into postural instability and gait disorder (PIGD, n = 36), intermediate (I, n = 22), and tremor-dominant (TD, n = 17) subtypes. The levels of UA and striatal DAT were compared across subtypes and the correlation between these two measures was also explored. We found that PIGD patients had lower levels of UA (3.7 vs 4.5 vs 5.3 mg/dL; P<0.001) and striatal DAT than patients with an intermediate or TD phenotype. Furthermore, UA levels significantly correlated with the levels of striatal DAT. We also observed that some PIGD (25%) and I (45%) patients had a predominance of tremor at disease onset. We speculate that UA might be involved in the maintenance of the less damaging TD phenotype and thus also in the conversion from TD to PIGD. Low levels of this natural antioxidant could lead to a major neuronal damage and therefore influence the conversion to a more severe motor phenotype.


Neurofibromatosis 1 and 2.
Neurofibromatosis (NF) 1 and 2 are multisystem disorders associated with a variety of neoplastic and non-neoplastic manifestations that typically progress in severity during the lifetime of the affected patient. The importance of appropriately diagnosing these disorders stems from the fact that the natural history of an associated neoplasm, such as a peripheral nerve tumor or an optic glioma, may be significantly different depending on whether or not the lesion arises in a person with NF. In addition, the indications for therapeutic intervention, hierarchy of treatment options and long-term management goals may differ substantially for patients with NF-related versus sporadic tumors. Finally, recognition of the diagnosis comprises an essential step for providing appropriate multidisciplinary evaluation and counseling to affected patients and their families. This article addresses the principal manifestations of these disorders and provides a contemporary review of the diagnostic and therapeutic issues that arise in children with NF1 and NF2.


Benefits of different drug formulations in psychopharmacology.
Adequate dosage forms are essential for achieving successful pharmacotherapy. Innovative dosage forms or delivery systems may direct a drug to its specific site of action, optimize the timing of the drug release, or increase comfort or convenience for the patient. Thus, such innovations may improve efficacy and tolerability and lead to improvements in health-related quality of life. Specialized dosage forms (e.g., depot injections, extended-release formulations) of several psychiatric agents have been extensively used. The latest addition is an orally disintegrating formulation of the antidepressant mirtazapine. This dosage form dissolves rapidly in the mouth and is convenient for the large proportion of patients who have difficulty in swallowing tablets.


A Multicenter Cross-Sectional Study on Assessment of Depression in Cardiac Patients.
Cardiovascular diseases (CVDs) are considered the primary cause of mortality in Saudi Arabia and it is one of the major health concerns in the country. Depression can complicate, halt or even exacerbate the process of managing CVDs, making it harder to optimize the patient's condition. The main aim of this study is to assess the depression in cardiac patients. A cross-sectional observational study was conducted in 257 patients diagnosed with cardiovascular diseases. The study was conducted in two governmental hospitals in Tabuk, Saudi Arabia, from December 2021 to April 2022. Depression was assessed using the Arabic version of the CESD-R questionnaire. The mean age of the participants was 44.49 ± 12.99 years. Majority of patients were in the age group of 40-49 years (n = 92, 35.8%). More than half (53.3%) of the samples were female. The prevalence of depression among cardiac patients was 53.3%. The prevalence of depression was high among cardiac patients. It is strongly advised that routine examination and management of depression in cardiac patients be included in their regimens.


A Mixed-Methods Evaluation of a Community-Based Glaucoma Check Service in Hackney, London, UK.
To evaluate the uptake, feasibility and acceptability of a general practice-based optometrist-led glaucoma check service. The service targeted people of black Caribbean and black African descent aged 40-65 years, resident in Hackney, London, United Kingdom. The study used a mixed-method design, including analysis of service data, prospective audit of secondary care referrals patient survey, cost-consequence analysis, and interviews with staff involved in developing and implementing the service. A total of 3040 patients were invited to undergo the free check; 595 (19.6%) booked an appointment and 461 (15.2%) attended. Overall, 31 patients (6.8%) were referred to secondary care, of whom 22 attended and were assessed for glaucoma. Four were diagnosed with glaucoma and eight with suspected glaucoma, i.e. 2.6% of patients who underwent the check. The cost per patient identified with suspected or confirmed glaucoma was £9,013. Staff who were interviewed suggested that patients who attended might be those who routinely attended optometrist appointments, however only 62.4% of survey respondents reported having had an eye examination in the previous two years, and 11.4% of women and 16.0% of men reported never having had an eye examination. This study represents one possible configuration for a glaucoma case-finding service, and it contributes to a wider debate about whether screening, targeted or otherwise, should be offered in the UK. Our findings suggest that general practice is an acceptable setting and that such a service may reach some people not previously engaged with primary eye care services.


The RNase III enzyme DROSHA is essential for microRNA production and spermatogenesis.
DROSHA is a nuclear RNase III enzyme responsible for cleaving primary microRNAs (miRNAs) into precursor miRNAs and thus is essential for the biogenesis of canonical miRNAs. DICER is a cytoplasmic RNase III enzyme that not only cleaves precursor miRNAs to produce mature miRNAs but also dissects naturally formed/synthetic double-stranded RNAs to generate small interfering RNAs (siRNAs). To investigate the role of canonical miRNA and/or endogenous siRNA production in spermatogenesis, we generated Drosha or Dicer conditional knock-out (cKO) mouse lines by inactivating Drosha or Dicer exclusively in spermatogenic cells in postnatal testes using the Cre-loxp strategy. Both Drosha and Dicer cKO males were infertile due to disrupted spermatogenesis characterized by depletion of spermatocytes and spermatids leading to oligoteratozoospermia or azoospermia. The developmental course of spermatogenic disruptions was similar at morphological levels between Drosha and Dicer cKO males, but Drosha cKO testes appeared to be more severe in spermatogenic disruptions than Dicer cKO testes. Microarray analyses revealed transcriptomic differences between Drosha- and Dicer-null pachytene spermatocytes or round spermatids. Although levels of sex-linked mRNAs were mildly elevated, meiotic sex chromosome inactivation appeared to have occurred normally. Our data demonstrate that unlike DICER, which is required for the biogenesis of several small RNA species, DROSHA is essential mainly for the canonical miRNA production, and DROSHA-mediated miRNA production is essential for normal spermatogenesis and male fertility.


Alkali Release from Aggregates in Long-Service Concrete Structures: Laboratory Test Evaluation and ASR Prediction.
This paper proposes a simple model for predicting the development of deleterious expansion from alkali-silica reaction (ASR) in long-service concrete structures. This model is based on some composition and reactivity parameters related to ASR, including the long-term alkali contribution by aggregates to concrete structures. This alkali contribution was estimated by means of a laboratory extraction test, appositely developed in this study in order to maximize the alkali extraction within relatively short testing times and with low leaching solution/aggregate ratios. The proposed test is a modification of the Italian Standard test method UNI 11417-2 (Ente Nazionale Italiano di Normazione) and it consists of subjecting an aggregate sample to leaching with saturated calcium hydroxide solution in a laboratory autoclave at 105 °C. Nine natural ASR-susceptible aggregates (seven sands and two coarse aggregates) were tested and the following optimized test conditions were found: leaching solution/aggregate weight ratio = 0.6; solid calcium hydroxide/aggregate weight ratio = 0.05; test duration = 120 h. The results of the optimized alkali extraction tests were used in the proposed model for predicting the potential development of long-term ASR expansion in concrete dams. ASR predictions congruent with both the field experience and the ASR prevention criteria recommended by European Committee for Standardization Technical Report CEN/TR 16349:2012 were found, thus indicating the suitability of the proposed model.


Diagnosis of female diverticula using magnetic resonance imaging.
We investigate the ability of physical exam to diagnose urethral diverticula with or without magnetic resonance imaging (MRI) and exclusive of invasive modalities. A retrospective chart review of all women undergoing urethral diverticulectomy at our institution since 1999 was performed. We identified 28 female patients with a mean age at diagnosis of 42.6 years (range 18-66). Common presenting symptoms included dyspareunia, urgency, and frequency. Physical exam revealed a suspected urethral diverticulum in 26 (92.9%) patients, which was confirmed postoperatively in 17 of the 20 (85%) women who underwent surgical resection. Noninvasive imaging modalities (MRI or CT) were available for review in 20 (71%) cases and made the correct diagnosis of urethral diverticulum (presence or absence) in 19 (95%) patients. In those patients with symptoms of stress or urge incontinence (11, 39%), voiding cystourethrogram (VCUG) was performed. Urethral diverticula are often easily diagnosed on physical exam. MRI can be a useful adjunct for defining diverticular extent in surgical planning, especially for proximal and complex diverticula, and should be the modality of choice if clinical suspicion is high based on patient symptoms and physical exam.


HPMA-based polymer therapeutics improve the efficacy of surgery, of radiotherapy and of chemotherapy combinations.
To assist intravenously administered anticancer agents in achieving proper circulation times and tumor concentrations, and to thereby improve the balance between their efficacy and their toxicity, a large number of drug delivery systems have been designed and evaluated over the years. Clinically relevant examples of such nanometer-sized carrier materials are liposomes, polymers, micelles and antibodies. In the vast majority of cases, however, and especially in patients, nanomedicine formulations are only able to attenuate the toxicity of the conjugated or entrapped chemotherapeutic drug, and they generally fail to improve the efficacy of the intervention. To overcome this shortcoming, and to broaden the clinical applicability of tumor-targeted nanomedicines, in the past 5 years we have developed several concepts for using N-(2-hydroxypropyl)methacrylamide (HPMA)-based polymer therapeutics to enhance the efficacy of combined modality anticancer therapy. Regarding surgery, HPMA copolymers were shown to be able to improve the retention of intratumorally administered chemotherapeutic agents at the pathological site, and to thereby increase their therapeutic index. Regarding radiotherapy, a synergistic interaction was observed, with radiotherapy improving the tumor accumulation of the copolymers, and with copolymers improving both the efficacy and the tolerability of radiochemotherapy. Futhermore, regarding chemotherapy combinations, we have for the first time provided in vivo evidence showing that passively tumor-targeted polymeric drug carriers can be used to deliver two different drugs to tumors simultaneously. Based on these findings, and on the fact that the concepts developed are considered to be broadly applicable, we conclude that nanomedicine formulations are highly suitable systems for improving the efficacy of combined modality anticancer therapy.


Identification of the Crucial Gene in Overflow Arteriovenous Fistula by Bioinformatics Analysis.
Objective: The aim was to study the preliminary screening of the crucial genes in intimal hyperplasia in the venous segment of arteriovenous (AV) fistula and the underlying potential molecular mechanisms of intimal hyperplasia with bioinformatics analysis. Methods: The gene expression profile data (GSE39488) was analyzed to identify differentially expressed genes (DEGs). We performed Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis of DEGs. Gene set enrichment analysis (GSEA) was used to understand the potential activated signaling pathway. The protein-protein interaction (PPI) network was constructed with the STRING database and Cytoscape software. The Venn diagram between 10 hub genes and gene sets of 4 crucial signaling pathways was used to obtain core genes and relevant potential pathways. Furthermore, GSEAs were performed to understand their biological functions. Results: A total of 185 DEGs were screened in this study. The main biological function of the 111 upregulated genes in AV fistula primarily concentrated on cell proliferation and vascular remodeling, and the 74 downregulated genes in AV fistula were enriched in the biological function mainly relevant to inflammation. GSEA found four signaling pathways crucial for intimal hyperplasia, namely, MAPK, NOD-like, Cell Cycle, and TGF-beta signaling pathway. A total of 10 hub genes were identified, namely, EGR1, EGR2, EGR3, NR4A1, NR4A2, DUSP1, CXCR4, ATF3, CCL4, and CYR61. Particularly, DUSP1 and NR4A1 were identified as core genes that potentially participate in the MAPK signaling pathway. In AV fistula, the biological processes and pathways were primarily involved with MAPK signaling pathway and MAPK-mediated pathway with the high expression of DUSP1 and were highly relevant to cell proliferation and inflammation with the low expression of DUSP1. Besides, the biological processes and pathways in AV fistula with the high expression of NR4A1 similarly included the MAPK signaling pathway and the pathway mediated by MAPK signaling, and it was mainly involved with inflammation in AV fistula with the low expression of NR4A1. Conclusion: We screened four potential signaling pathways relevant to intimal hyperplasia and identified 10 hub genes, including two core genes (i.e., DUSP1 and NR4A1). Two core genes potentially participate in the MAPK signaling pathway and might serve as the therapeutic targets of intimal hyperplasia to prevent stenosis after AV fistula creation.


Glycosylation of human alpha 1-antitrypsin in Saccharomyces cerevisiae and methylotrophic yeasts.
Human alpha 1-antitrypsin (alpha 1-AT) is a major serine protease inhibitor in plasma, secreted as a glycoprotein with a complex type of carbohydrate at three asparagine residues. To study glycosylation of heterologous proteins in yeast, we investigated the glycosylation pattern of the human alpha 1-AT secreted in the baker's yeast Saccharomyces cerevisiae and in the methylotrophic yeasts, Hansenula polymorpha and Pichia pastoris. The partial digestion of the recombinant alpha 1-AT with endoglycosidase H and the expression in the mnn9 deletion mutant of S. cerevisiae showed that the recombinant alpha 1-AT secreted in S. cerevisiae was heterogeneous, consisting of molecules containing core carbohydrates on either two or all three asparagine residues. Besides the core carbohydrates, variable numbers of mannose outer chains were also added to some of the secreted alpha 1-AT. The human alpha 1-AT secreted in both methylotrophic yeasts was also heterogeneous and hypermannosylated as observed in S. cerevisiae, although the overall length of mannose outer chains of alpha 1-AT in the methylotrophic yeasts appeared to be relatively shorter than those of alpha 1-AT in S. cerevisiae. The alpha 1-AT secreted from both methylotrophic yeasts retained its biological activity as an elastase inhibitor comparable to that of alpha 1-AT from S. cerevisiae, suggesting that the different glycosylation profile does not affect the in vitro activity of the protein.


Perceived fatigue for short- and long-haul flights: a survey of 739 airline pilots.
Fatigue-related incidents in aviation may be self-reported by pilots in confidential systems. The aim of this study was to clarify what fatigue means to pilots on short- and long-haul flights (SHF and LHF, respectively). Questionnaires were distributed to pilots through four airlines. Questions concerned the perceived causes of fatigue, its signs and symptoms in the reporting pilot and observed in others, as well as the strategies used to minimize its impact. Of 3,436 questionnaires distributed, 739 (21.5%) were returned. For LHF, fatigue was seen as mainly due to night flights (59%) and jet lag (45%). For SHF, fatigue was caused by prolonged duty periods (multi-segment flights over a sequence of 4 to 5 d) (53%) and successive early wake-ups (41%). Self-reported manifestations of fatigue in 60% of LHF pilots and 49% of SHF pilots included reduction in alertness and attention, and a lack of concentration. Signs observed in other crewmembers included an increase in response times and small mistakes (calculation, interpretation). When pilots were tired, all the flying tasks seemed to be more difficult than usual. In both LHF and SHF, rest and sleep management were the primary strategies used to cope with fatigue. Analysis showed that duty time is a major predictor of fatigue, but that it cannot be considered independently from the other contributory factors. For both LHF and SHF, pilots reported acute fatigue related to sleep deprivation, due mainly to work schedules: night flights, jet-lag, and successive early wake-ups. These causal factors could easily be assessed in investigation of accidents and incidents.


Measurement of central and peripheral dynamic visual acuity thresholds during ocular pursuit of a moving target.
Previously, visual acuity thresholds for eccentric retinal points have been documented for targets that oscillate while the observer fixates a central point. This research describes the situation where the observer tracks a moving target in constant linear motion, thereby involving the pursuit and saccadic eye movements. The increase of visual acuity thresholds with target motion (0 to 70 degrees/s) was evaluated as a function of retinal eccentricity. Nine retinal points were evaluated, (central, 5 degrees and 10 degrees nasal, 5 degrees and 10 degrees temporal, 5 degrees and 10 degrees superior, and 5 degrees and 10 degrees inferior to the fovea). Eight normal subjects viewed computer-generated randomly oriented E's monocularly through a horizontally rotating mirror. A computer automatically calculated the minimal angle of resolution (MAR) threshold values. Result indicated that the change in visual acuity thresholds was dependent upon retinal location. The thresholds for central and peripheral eccentricities plotted as a function of angular velocity were linear but the slope of the linear function was much reduced for peripherally viewed targets compared to centrally viewed targets. Although both peripheral and central visual acuity thresholds may increase with increasing target velocity due to velocity mismatch errors and saccadic suppression and/or omission, the reduction in slope for peripherally viewed targets may be due to differential temporal summation, retinal smear, and/or separate retinogeniculate pathway processing.


Thermal-noise effect on the transition to Rayleigh-Bénard convection.
We report measurements of fluctuation and roll patterns near the transition to Rayleigh-Bénard convection which are consistent with a fluctuation-induced first-order transition, as predicted by Swift and Hohenberg. Above onset, we find convection rolls with noise-induced fluctuations, time-dependent amplitude modulation and roll undulation, and homogeneous dislocation nucleation.


Dispersion control in plasmonic open nanocavities.
We experimentally demonstrate the dependence of plasmonic resonant properties on cavity height in open circular cylinder nanocavities as a result of a strong three-dimensional confinement of the electromagnetic field, which shows a new way to tailor the dispersion of surface plasmon polaritons in cavities. The azimuthal and the axial symmetric plasmonic mode patterns are directly observed at resonant wavelengths using cathodoluminescence spectroscopy. Plasmonic modes and optical vertical cavity modes can be simultaneously excited and can coexist in a nanocavity with sufficient height. The highest quality factor, which is up to 73, is obtained in a 500 nm high cavity. The smallest mode volume is only 0.031 λ(SPP)(3), and the corresponding Purcell factor is 71. Open nanocavities provide space for the interaction between an optical emitter and a confined electromagnetic field. Many applications can be expected, such as plasmonic light-emitting devices and nanolasers.


The role of phenotyping and replication capacity in anti-HIV therapeutics.
The management of antiretroviral-experienced and -naive HIV-infected patients is becoming increasingly complex with the emergence of multidrug-resistant viruses and with the inter-relationships between numerous virological, immunological and therapeutic factors. In addition to standard surrogate markers of peripheral CD4+ T-cell counts and plasma viral loads, viral resistance phenotype, replication capacity and genotype assays serve as objective measures of viral properties, which presumably reflect, to a certain degree, what is occurring in vivo. This review explores the principles behind, and the basic science and clinical evidence supporting the application of viral resistance phenotypic assays and replication capacity assays in the therapeutic management of HIV disease.


Determination of cyanide and cyanogenic compounds in biological systems.
A survey of methods for the qualitative and quantitative determination of cyanide and cyanogenic compounds is presented. Particular attention is paid to determination in complex matrices. Chromatographic methods able to separate mixtures of closely related structures, such as glycosides of enantiomeric hydroxynitriles or lipids with slightly differing fatty acid spectra, are included, as are highly selective methods of detection, such as enzymic post-column cleavage combined with electrochemical detection as used in high-performance liquid chromatography. Details of thin-layer chromatography, including methods for detection, are given for both straight-phase and reverse-phase systems. The survey includes simple field methods as well as automated laboratory methods for the determination of 'free', 'bound' and 'total' cyanide, for example in processed food products from Manihot esculenta Cranz. Sources of enzymes are listed and attention is given to problems of sample storage and preparation. References are given to review articles which include data from methods such as ultraviolet, infrared and proton and carbon-13 nuclear magnetic resonance spectroscopies.


Unidentified N-glycans by N-glycosidase A were Identified by Nglycosidase F under Denaturing Conditions in Plant Glycoprotein.
The identification of N-glycans in plant glycoproteins or plant-made pharmaceuticals is essential for understanding their structure, function, properties, immunogenicity, and allergenicity (induced by plant-specific core-fucosylation or xylosylation) in the applications of plant food, agriculture, and plant biotechnology. N-glycosidase A is widely used to release the Nglycans of plant glycoproteins because the core-fucosylated N-glycans of plant glycoproteins are hydrolyzed by N-glycosidase A but not by N-glycosidase F. However, the efficiency of Nglycosidase A activity in plant glycoproteins remains unclear. The aim of the study was to elucidate the efficient use of N-glycosidases to identify and quantify the N-glycans of plant glycoproteins; it aimed at identification of released N-glycans by Nglycosidase F and assessment of their relative quantities with a focus on unidentified N-glycans by N-glycosidase A in plant glycoproteins, Phaseolus vulgaris lectin (PHA) and horseradish peroxidase (HRP). Liquid chromatography-tandem mass spectrometry was used to analyze and compare the N-glycans of PHA and HRP treated with either N-glycosidase A or F under denaturing conditions. The relative quantities (%) of each N-glycan (>0.1%) to the total N-glycans (100%) were determined. N-glycosidase A and F released 9 identical N-glycans of PHA, but two additional corefucosylated N-glycans were released by only N-glycosidase A, as expected. By contrast, in HRP, 8 N-glycans comprising 6 core-fucosylated N-glycans, 1 xylosylated N-glycan, and 1 mannosylated N-glycan were released by N-glycosidase A. Moreover, 8 unexpected N-glycans comprising 1 corefucosylated N-glycan, 4 xylosylated N-glycans, and 3 mannosylated N-glycans were released by Nglycosidase F. Of these, 3 xylosylated and 2 mannosylated N-glycans were released by only Nglycansodase F. These results demonstrate that N-glycosidase A alone is insufficient to release the Nglycans of all plant glycoproteins, suggesting that to identify and quantify the released N-glycans of the plant glycoprotein HRP, both N-glycosidase A and F treatments are required.


Phytotoxicity of constituents of glandular trichomes and the leaf surface of camphorweed, Heterotheca subaxillaris.
Camphorweed, Heterotheca subaxillaris (Lam.) Britt. & Rusby, has a camphor-like odor, and its leaf surfaces contain glandular trichomes of the type shown to contain high levels of isoprenoids in other species. Borneol (1), the phytotoxic calamenene-type sesquiterpenes (2-5, 9-11), and methylated flavones (12-15) were isolated from the dichloromethane rinsate of camphorweed aerial tissues. The strongest plant growth inhibitor against Agrostis stolonifera and Lactuca sativa seedlings, as well as duckweed (Lemna pausicostata), was 2-methoxy-calamenene-14-carboxylic acid (2). Esterification of calamenene carboxylic acids decreased their biological activity.


The role of the AR/ER ratio in ER-positive breast cancer patients.
The significance of androgen receptor (AR) in breast cancer (BC) management is not fully defined, and it is still ambiguous how the level of AR expression influences oestrogen receptor-positive (ER+) tumours. The aim of the present study was to analyse the prognostic impact of AR/ER ratio, evaluated by immunohistochemistry (IHC), correlating this value with clinical, pathological and molecular characteristics. We retrospectively selected a cohort of 402 ER+BC patients. On each tumour, IHC analyses for AR, ER, PgR, HER2 and Ki67 were performed and AR+ cases were used to calculate the AR/ER value. A cut-off of ≥2 was selected using receiver-operating characteristic (ROC) curve analyses. RNA from 19 cases with AR/ER≥2 was extracted and used for Prosigna-PAM50 assays. Tumours with AR/ER≥2 (6%) showed more frequent metastatic lymph nodes, larger size, higher histological grade and lower PgR levels than cases with AR/ER<2. Multivariate analysis confirmed that patients with AR/ER≥2 had worse disease-free interval (DFI) and disease-specific survival (DSS) (hazard ratios (HR) = 4.96 for DFI and HR = 8.69 for DSS, both P ≤ 0.004). According to the Prosigna-PAM50 assay, 63% (12/19) of these cases resulted in intermediate or high risk of recurrence categories. Additionally, although all samples were positive for ER assessed by IHC, the molecular test assigned 47.4% (9/19) of BCs to intrinsic non-luminal subtypes. In conclusion, the AR/ER ratio ≥2 identifies a subgroup of patients with aggressive biological features and may represent an additional independent marker of worse BC prognosis. Moreover, the Prosigna-PAM50 results indicate that a significant number of cases with AR/ER≥2 could be non-luminal tumours.


Effects of cafeteria diet and high fat diet intake on anxiety, learning and memory in adult male rats.
The effects of cafeteria and high fat diets were investigated on animal models of behavior. Male Wistar rats were treated with Control (C), Cafeteria (CD) and High Fat (FD) diets and tested in the Elevated Plus-Maze (EPM) and Morris Water Maze (MWM) procedures. Body weight, length, abdominal circumference, retroperitoneal and epididymal adipose tissues were recorded. Physical parameters, weight of tissues, EPM, and MWM data were subjected to ANOVA followed by Newman-Keuls test (P < 0.05). There were no differences on weight and length parameters between CD and C rats up to 98 days of age. However, abdominal circumferences were higher in CD as compared to C at 35 and 70 days of age, respectively, the 5th and the 7th weeks. FD presented lower measures of weight and abdominal circumference; nevertheless there was an increase on those parameters at the end of the nutritional treatment. Even without an apparent weight gain of CD and FD these animals presented a greater accumulation of retroperitoneal and epididymal adipose tissues. In addition, CD and FD demonstrated behaviors that can suggest lower anxiety. CD showed a better learning performance and FD showed better recall of previous learned information in the memory retention test. According to those data it was concluded that hypercaloric diet ingestion was capable of triggering metabolic alterations and possibly lowering anxiety associated to learning or memory improvement on a spatial task.


A novel heterozygous ITGB3 p.T720del inducing spontaneous activation of integrin αIIbβ3 in autosomal dominant macrothrombocytopenia with aggregation dysfunction.
We identified a novel heterozygous ITGB3 p.T720del mutation in a pedigree with macrothrombocytopenia exhibiting aggregation dysfunction. Platelet aggregation induced by ADP and collagen was significantly reduced, while ristocetin aggregation was normal. Integrin αIIbβ3 was partially activated in a resting status, but platelet expression of αIIbβ3 was downregulated. Functional analysis using a cell line showed spontaneous phosphorylation of FAK in αIIb/β3 (p.T720del)-transfected 293T cells in suspension conditions. Abnormal cytoplasmic protrusions, membrane ruffling, and cytoplasmic localization of αIIbβ3 were observed in αIIb/β3 (p.T720del)-transfected CHO cells. Such morphological changes were reversed by treatment with an FAK inhibitor. These findings imply spontaneous, but partial, activation of αIIbβ3 followed by phosphorylation of FAK as the initial mechanism of abnormal thrombopoiesis. Internalization and decreased surface expression of αIIbβ3 would contribute to aggregation dysfunction. We reviewed the literature of congenital macrothrombocytopenia associated with heterozygous ITGA2B or ITGB3 mutations. Reported mutations were highly clustered at the membrane proximal region of αIIbβ3, which affected the critical interaction between αIIb R995 and β3 D723, resulting in a constitutionally active form of the αIIbβ3 complex. Macrothrombocytopenia caused by a heterozygous activating mutation of ITGA2B or ITGB3 at the membrane proximal region forms a distinct entity of rare congenital thrombocytopenia.


Optimal process configuration for anaerobic digestion with ozonation.
Economical source minimization of excess sludge production is an attractive option to deal with the problem of sludge disposal under strict disposal standards. In this paper long-term operational results for two different process configurations that combine oxidative ozone treatment with anaerobic sludge digestion are described. In the first configuration ozone pretreatment was combined with chemostat anaerobic digestion while in the second configuration ozone pre/post-treatments were combined with an anaerobic digester operated without solid removal. From the results of chemostat experiments, the ozone pretreatment solubilized around 19% and 37% of the solids at 0.015 and 0.05 gO3/gTS ozone dose respectively. The ozone pretreatment resulted in improved TVS reduction efficiencies and the degradation efficiencies were observed to depend on the applied ozone dose and system SRT. The TVS degradation efficiency for pre-ozonated sludge at an ozone dose of 0.05 gO3/gTS was 59% as compared to 31% for the control reactor fed with un-ozonated sludge. Test results with the second configuration indicated that overall TVS removal efficiencies for a process scheme with post-ozonation could be improved up to 85% with a minimum ozone dose of 0.045 gO3/gTVS-fed. However, since no solids (except that for sampling) were withdrawn in this configuration, the accumulated total solids in the reactors increased to 28 g/l to 30 g/l at pseudosteady state. The average specific methane recoveries were observed to be 0.36 lCH4/gTVS fed which were slightly lower than theoretically expected. Based on the experimental results, important points in the choice of process configuration are discussed.


Identification of MALT1 as both a prognostic factor and a potential therapeutic target of regorafenib in cholangiocarcinoma patients.
Intrahepatic cholangiocarcinoma (CCA) is an aggressive cancer that lacks an effective targeted therapy. Here, we assessed the therapeutic efficacy of regorafenib in CCA, as well as elucidated its underlying mechanism. We first demonstrated that regorafenib not only inhibited growth but also induced apoptosis in human CCA cells. Subsequently, we used in silico approaches to identify MALT1 (Mucosa-associated lymphoid tissue protein 1), which plays an important role in activating NF-κB, as a potential target of regorafenib. Overexpression of Elk-1, but not Ets-1, in HuCCT1 cells markedly reduced their sensitivity to regorafenib, which might be attributed to a significant increase in MALT1 levels. Our results further demonstrated that this drug drastically inhibited MALT1 expression by suppressing the Raf/Erk/Elk-1 pathway. The efficacy of regorafenib in decreasing in vivo CCA growth was confirmed in animal models. Regorafenib efficacy was observed in two MALT1-positive CCA patients who failed to respond to several other lines of therapy. Finally, MALT1 was also identified as an independent poor prognostic factor for patients with intrahepatic CCA. In conclusion, our study identified MALT1 to be a downstream mediator of the Raf/Erk/Elk-1 pathway and suggested that MALT1 may be a new therapeutic target for successful treatment of CCA by regorafenib.


Functionalization of Mesoporous Carbon Materials for Selective Separation of Lanthanides under Acidic Conditions.
New functional mesoporous carbon sorbents were successfully synthesized to overcome some issues of solid-liquid extraction (e.g., selectivity, extraction capacity, and reusability under acidic conditions) in production of pure lanthanides (Ln). Wet-oxidation technique was performed to increase the surface reactivity of pristine ordered mesoporous carbon (OMC), and, in a second step, a surface modification using diglycolamide-based (DGA-based) selective ligands toward Ln was performed. Two types of ligands were tested: the first contains a long spacer (e.g., between carbon support and chelating function), and the second has a shorter one. These materials have been characterized by X-ray photoelectron spectroscopy (XPS), low-angle X-ray diffraction (XRD), thermogravimetric analysis, nitrogen sorption, transmission electron microscopy (TEM), and scanning electron microscopy (SEM). These analyses confirmed that the carbon mesostructure was maintained after organo-functionalization of the surface and showed the covalent attachment of selective ligands. These new materials, and especially the system with a short spacer between the ligand and the surface, reveal unique Ln selectivity profiles with improved extraction performances for the recovery of lanthanides, in terms of both selectivity and adsorption capacity, and unprecedented stability under acidic conditions.


Large pyogenic granuloma: a case report.
Though pyoginic granuloma is a common occurrence in the oral cavity, it has got particular significance because of its unexpected clinical course. Here a case of large pyogenic granoloma is presented in a 30-year-old female reported at the dental OPD of VSS Medical College and Hospital, Burla with the complaint of a growth in the mouth from the right upper last tooth since one and half years associated with difficulty in swallowing and breathing. The lesion was excised under local anaesthesia along with extraction of upper right second molar. The patient recovered without any complication and there was no recurrence even after one year.


Synthesis, structure and density functional theory calculations of a novel photoluminescent trisarylborane-bismuth(III) complex.
A novel trisarylborane-Bi(III) complex, tris(4-(dimesitylboryl)phenyl)bismuthine [Bi(PhBMes2 )3 ], in which (Ph = phenyl, and Mes = mesityl), was synthesized via the reaction of bismuth (III) chloride (BiCl3 ) with three equivalents of lithiated (4-bromophenyl)- dimesitylborane [BrPhBMes2 ]. The new trisarylbismuthine was characterized by elemental analysis, ultraviolet-visible (UV-vis) spectroscopy, and NMR (1 H and 13 C) spectroscopy. The molecular structure of Bi(PhBMes2 )3 in the solid state was determined using single-crystal X-ray diffraction analysis, which showed short intermolecular C-H···H-C contact. The complex is a fluorescent emitter (λmax = 395 nm) at room temperature and a phosphorescent emitter (λmax = 423 nm) at 77 K, which displayed a long lifetime of 495 ms. The UV-vis transitions were investigated using density function theory (DFT) and time-dependent (TD)-DFT calculations. Natural bond orbital analysis showed that the bismuth (III) center was mainly Lewis acidic in nature.


Parietal lobe critically supports successful paired immediate and single-item delayed memory for targets.
The parietal lobe is important for successful recognition memory, but its role is not yet fully understood. We investigated the parietal lobes' contribution to immediate paired-associate memory and delayed item-recognition memory separately for hits (targets) and correct rejections (distractors). We compared the behavioral performance of 56 patients with known parietal and medial temporal lobe dysfunction (i.e. early Alzheimer's Disease) to 56 healthy control participants in an immediate paired and delayed single item object memory task. Additionally, we performed voxel-based morphometry analyses to investigate the functional-neuroanatomic relationships between performance and voxel-based estimates of atrophy in whole-brain analyses. Behaviorally, all participants performed better identifying targets than rejecting distractors. The voxel-based morphometry analyses associated atrophy in the right ventral parietal cortex with fewer correct responses to familiar items (i.e. hits) in the immediate and delayed conditions. Additionally, medial temporal lobe integrity correlated with better performance in rejecting distractors, but not in identifying targets, in the immediate paired-associate task. Our findings suggest that the parietal lobe critically supports successful immediate and delayed target recognition memory, and that the ventral aspect of the parietal cortex and the medial temporal lobe may have complementary preferences for identifying targets and rejecting distractors, respectively, during recognition memory.


High-resolution calorimetry in pulsed magnetic fields.
We have developed a new calorimeter for measuring the thermodynamic properties in pulsed magnetic fields. Instrumental design is described along with the instrument construction details, including the sensitivity of a RuO2 thermometer. Operation of the calorimeter is demonstrated by measuring the heat capacity of three samples: pure germanium, CeCu2Ge2, and κ-(BEDT-TTF)2Cu[N(CN)2]Br, in pulsed fields up to 43.5 T. Obtaining field stability is key in measuring high-resolution heat capacity under pulsed fields. We also examine the performance of the calorimeter by employing two measurement techniques: the quasi-adiabatic and dual-slope techniques. We demonstrate that the calorimeter developed in this study is capable of performing high-resolution calorimetry in pulsed magnetic fields, which opens the door to new opportunities for high-field thermodynamic studies.


Efficacy of probiotic supplementary therapy for asthma, allergic rhinitis, and wheeze: a meta-analysis of randomized controlled trials.
Background: Probiotic supplementary therapy to prevent allergic diseases, including asthma in children, has been widely explored in many randomized controlled trials. However, there is conflicting evidence on the effect of probiotic supplementation during pregnancy and infancy to the incidence of asthma and allergic rhinitis. Method: This study was designed to systematically explore the potential effects of probiotic supplementation on the occurrence and development of asthma, wheeze, and allergic rhinitis. Randomized controlled trials were searched in several medical literature data bases. A meta-analysis was undertaken by using the fixed-effects model or the random effects model to calculate the pooled risk of significant heterogeneity. Two writers were designated to perform the study selection and data extraction. The primary outcome was clinically diagnosed asthma; the secondary outcomes included wheeze, allergic rhinitis, and a positive aeroallergen skin-prick test result. Results: Seventeen randomized controlled trials, which composed a total of 5264 children, were analyzed. The pooled data for risk of developing asthma after probiotic supplementation showed no significant reduction compared with controls (risk ratio [RR] 0.86 [95% confidence interval {CI}, 0.73-1.01]; I² = 0%; p = 0.06). A subgroup of strains indicated that Lactobacillus rhamnosus GG supplementation only had a reduction to the occurrence of asthma (RR 0.75 [95% CI, 0.57-0.99]; I² = 11%; p = 0.04). The supplement in the postnatal group had a similar result, but the incorporated data were limited. Meanwhile, it is failed to identify that probiotic supplementary therapy have a clear benefit to the secondary outcomes: wheeze, allergic rhinitis, positive aeroallergen skin-prick test result. Conclusion: This study showed a significant benefit that supplementation with probiotics in pre- and postnatal periods was likely to play an essential strategic role in the prevention of asthma. However, these effects were based on the type of probiotics used, which also need more large-sample and high-quality RCTs to confirm the reliability of this study.


Effects of 4-nonylphenol and/or diisononylphthalate on THP-1 cells: impact of endocrine disruptors on human immune system parameters.
The aim of the present work is to investigate the link between two endocrine disruptor compounds (EDCs), which are chemicals that interfere with the hormone system in human and wildlife, and the human immune response through a study of their effects on the THP-1 human cell line which was used as a model for macrophages. We used two EDCs, diisononylphthalate (DiP) and 4-n-nonylphenol (NP) alone or in combination in order to evaluate the effects of these compounds on several parameters of the immune response - cytokine secretion, phagocytosis and the putative implication of the estrogen receptors - by studying the level of MAPK activation. NP and DiP strongly reduced phagocytosis and modify cytokine secretions. Indeed, differentiated THP-1 cell exposures (i) to 5 and 10 microM of combination of NP and DiP induced an IL-8 level in the medium respectively of 28.9 and 45 percent higher than the level obtained for the control (untreated cells), (ii) to combination of NP and DiP at 10 microM induced an increase of IL-1β level in comparison to the control level, (iii) to combination of NP and DiP induced an increase of TNF-α level whatever the concentration of EDCs tested (between 0 and 10 microM). Lastly, differentiated THP-1 cell exposure to NP, DiP alone or in combination (2 microM for each condition) induced a decrease of ERK1/2 phosphorylation in comparison to ERK1/2 phosphorylation level of the control. Moreover, differentiated THP-1 cell treatments by ICI-182780 (an estrogen receptor antagonist) supressed the EDC effects on ERK1/2 phosphorylation level which indicates an estrogen receptor-dependent pathway. These results suggest that EDCs have the ability to alter the human immune function, maybe by interfering with endocrine balance.


SIRT1 prevents pulmonary thrombus formation induced by arachidonic acid via downregulation of PAF receptor expression in platelets.
SIRT1, a class III histone deacetylase, is critically involved in cellular response to stress and modulates cardiovascular risk factors. However, its role in thrombus formation is largely unknown. Thus, this study investigated the effect of SIRT1 on pulmonary thrombus formation, and then identified its role in the modulation of platelet aggregation. In isolated human platelets, cell aggregation was increased by various platelet activators, such as platelet activating factor (PAF), arachidonic acid (AA), ADP, and thrombin. AA- and PAF-mediated platelet aggregations were suppressed by WEB2086, a PAF receptor (PAFR) antagonist. Pulmonary thrombus formation induced by PAF or AA was also attenuated by WEB2086, suggesting that PAFR plays a key role in AA-induced platelet aggregation. In platelets isolated from SIRT1-TG mice as well as in platelets treated with resveratrol or reSIRT1, PAFR expression was decreased, whereas this expressional downregulation by SIRT1 activators was inhibited in platelets treated with MG132 (a proteasome inhibitor) or NH4Cl (a lysosome inhibitor). Furthermore, platelet aggregation induced by AA was markedly attenuated by resveratrol and reSIRT1. Likewise, the increased pulmonary thrombus formation in mice treated with AA was also attenuated by SIRT1 activators. In line with these results, pulmonary thrombus formation was markedly attenuated in SIRT1-TG mice. Taken together, this study showed that SIRT1 downregulates PAFR expression on platelets via proteasomal and lysosomal pathways, and that this downregulation inhibits platelet aggregation in vitro and pulmonary thrombus formation in vivo.


Neuropeptides as biologial system integrators – mini review.
This paper provides a review on the emerging role of neuropeptides for body systems integration. Neuropeptides are small protein-like substances that are released into the synaptic space and/or the blood, hence, acting as neurotransmitters and neurohormones. Classically, their role has been viewed as integrating the central nervous system and the endocrine system. More recently, however, there is an emerging understanding that neuropeptides integrate many more body systems into a larger cohesive body response that involves basic body functions, behavior, and mind. One indication is the discovery that neurohormones are also produced by many peripheral tissues and that non-neuronal peptides are released by neurons as well. Examples from the gastrointestinal and the immune system are presented. With the emerging role of neuropeptides for systems integration, immense opportunities arise for their use as pharmacological agents and biomarkers in the diagnosis and treatment of countless disorders such as chronic inflammatory diseases and obesity.


Cone shell envenomation: epidemiology, pharmacology and medical care.
The marine environment presents much danger, specifically in regards to the numerous venomous inhabitants within tropical and subtropical waters. The toxins from one such group of venomous marine snails, commonly referred to as 'cone snails', have been well documented in causing human fatalities. Yet information regarding medical treatment for cone snail envenomation is limited and poorly accessible. To correct this, medical and scientific expertise and literary review on Conus provide a basic and comprehensive directive focused on the medical treatment and post-mortem investigative analysis of cone snail envenomation. We emphasize what we expect to be the most lethal feeding group of Conus and provide a brief background to the epidemiology of their stings. We describe the venom apparatus of Conus and its utility of rapid venom delivery. We have compiled the documented incidences of Conus envenomation to offer thorough reference of known signs and symptoms - this too drawing on personal experiences in the field. We have also made available a brief background to the biochemistry and pharmacology of Conus venoms to highlight their complex nature.


External hemorrhoidal disease in child and teenage: Clinical presentations and risk factors.
Hemorrhoidal disease (HD), though mostly seen in adults, has recently emerged as a common problem among children. However, the diagnosis and treatment of HD in children is mostly based on the data obtained in adult studies. In this study, we aimed to evaluate risk factors, diagnostic and treatment modalities in the children diagnosed with external HD. The study was conducted at Sakarya University Medical School Pediatric Surgery Department between January 2012 and July 2018. We reviewed children who were diagnosed as having HD at Pediatric Surgery clinic. Age, gender, presenting symptoms, physical examination findings, risk factors, and treatment outcomes were evaluated for each patient. The study included 56 patients with a mean age of 140.8±45.2 months. The patients comprised 48 (85.7%) boys and 8 (14.3%) girls. Constipation and a positive family history were the most common risk factor (n=33; 58.9%, n=29; 51.8%, respectively). Conservative treatment was performed in 53 (94.6%) patients. Recurrence was observed in 5 (8.9%) and skin tag was detected in 6 (10.7%) patients. External HD mostly occurs in boys in their second decade of life. Positive family history and constipation were the most common risk factors in our patients. Conservative treatment is sufficient for the management of external HD in children because of its low recurrence rates.


Interferon induction by RNA viruses and antagonism by viral pathogens.
Interferons are a group of small proteins that play key roles in host antiviral innate immunity. Their induction mainly relies on host pattern recognition receptors (PRR). Host PRR for RNA viruses include Toll-like receptors (TLR) and retinoic acid-inducible gene I (RIG-I) like receptors (RLR). Activation of both TLR and RLR pathways can eventually lead to the secretion of type I IFNs, which can modulate both innate and adaptive immune responses against viral pathogens. Because of the important roles of interferons, viruses have evolved multiple strategies to evade host TLR and RLR mediated signaling. This review focuses on the mechanisms of interferon induction and antagonism of the antiviral strategy by RNA viruses.


Artefact as the pathologist's friend: peritumoral retraction in in situ and infiltrating duct carcinoma of the breast.
Peritumoral retraction artefact appears in tissue sections as an empty space partially or completely encircling a nest of tumor cells, usually in conformity with the rounded or angular outline of that particular nest. The present study was designed to test this finding in a large series of cases and to quantify the appearance of peritumoral retraction artefact in, in situ and infiltrating duct carcinoma of the breast. We examined 199 cases of infiltrating duct carcinoma (IDC) and 188 cases of ductal carcinoma in situ (DCIS). Of the total of 387 cases, 111 were core needle biopsies, whereas the others were larger resections. In each specimen, retraction was evaluated on hematoxylin and eosin-stained slides as negative, 1+ (1% to 25% of tumor showing retraction), 2+ (26% to 50%), 3+ (51% to 75%), or 4+ (76% to 100%). Overall, peritumoral retraction was noted in 168 of 199 cases (84.4%) of IDC, versus 30 of 188 cases (16%) of DCIS (P < 0.0001). Peritumoral retraction scored as 2+ or greater (26% to 50%) was seen in only 1 of 188 DCIS specimens, compared with 77 of 199 IDC. Thus, peritumoral retraction artefact appears to be a significant finding seen during the evaluation of hematoxylin and eosin specimens for the diagnosis of carcinoma. We discuss the possibility that this phenomenon might represent true prelymphatic space involvement rather than a fixation artefact.


Use of the buccal fat pad as a pedicle graft.
A technique was developed to use the pedicle buccal fat pad as method for closing an oro-antral communication. The buccal fat pad is situated in the posterior part of the maxilla and bounded by the pterygopalatine fossa, buccal muscle, and masseter muscle. It is supplied by blood from small branches of the maxillary artery, the superficial temporal artery, and the facial artery. Generally, the buccal fat pad can be easily reached by a horizontal incision over the periosteum near the maxillary third molar. As much as 60 x 50mm2 can be obtained. For reconstructive surgery, the buccal fat pad is suitable for closing the sinus near the hard and soft palate and naso-oral fistulae. In our case, graft tissues after surgery healed satisfactorily, began to epithelialize at two weeks after operation, and appeared with normal mucous-like changes at about one month. Thus, the pedicle buccal fat pad is a safe, simple, convenient, and effective grafting method, if it is applied to appropriate cases.


An Australian validation study of the temperament and character inventory.
To assess the validity of the temperament and character inventory (TCI) measure in an Australian sample. A sample of depressed subjects completed the TCI and a measure assessing personality disorder constructs (PDCs), while family members and psychiatrists also returned PDC ratings. Factor analyses generally supported the TCI constructs, when the temperament and character scales were analysed separately. Self-reported PDC scores were validated against corroborative witness ratings and used to assess the TCIs concurrent validity. Validation analyses supported all TCI temperament scales, but the Self-transcendence Character scale was unassociated with PDC scores. The remaining two character scales (i.e. cooperativeness and self-directedness) were non-specifically associated with all PDC scores. Study results support the validity of the TCI scales, but question the best model for conceptualizing the TCI. It is suggested that two character scales quantify disordered functioning, while temperament scales quantify style, constructs that may be inter-related or independent in individual subjects.


Quantitation with chemical tagging reagents in biomarker studies.
Isobaric tags for relative and absolute quantitation (iTRAQ), Tandem Mass Tags (TMT) and related chemical tag reagents provide analytical platforms for quantitative proteomics applied to clinical samples. In this Viewpoint article, applications for discovery and targeted modes are discussed with an emphasis on study design and technical considerations in biomarker analysis. The evolution and promise of emerging, related strategies are also discussed. It should be noted that iTRAQ and TMT users contributed to the key debates in the biomarker field, to define strategies for biomarker discovery for identification of clinical biomarkers, and continue to inform design of verification and validation assays via implementation of non-isobaric variants for targeted analyses.


Thoracic vertebral body fracture after total hip replacement in diffuse idiopathic skeletal hyperostosis.
This article describes the critical clinical sequelae of a patient with diffuse idiopathic skeletal hyperostosis who sustained an acute iatrogenic thoracic vertebral body fracture with subsequent spinal cord injury after a total hip replacement, with a final lethal course.A 57-year-old woman was referred to the authors' institution after undergoing a total hip replacement in the supine position for secondary osteoarthritis. Postoperatively, the patient had symptoms of an incomplete paraplegia. Computed tomography scan and magnetic resonance imaging revealed diffuse idiopathic skeletal hyperostosis and an acute unstable fracture of T11 with spinal contusion. A posterior spinal fusion of T10-L1 with laminectomy of T11 was performed immediately on admission. Postoperatively, no improvement of the neurological deficit was observed. After developing multiorgan failure while in intensive care, the patient died 2 months after the total hip replacement.The morphological and functional symptoms of diffuse idiopathic skeletal hyperostosis with the typical ossification of the longitudinal ligaments and the associated loss of bending forces of the spine were detected postoperatively. This severe case demonstrates that the surgeon must be alert to possible complications due to intraoperative maneuvers in patients with stiffened spinal disorders undergoing total hip replacement.


Preparation of a Functional Rat LDL Receptor Minigene.
The majority of the low-density lipoprotein (LDL) receptors present in the body are expressed in the liver. Therefore, plasma LDL levels significantly correlate with changes in the activity of the hepatic LDL receptor. Based on this, there is a need to understand the regulatory mechanisms that control the hepatic expression of the low-density lipoprotein (LDL) receptor. Herein, we have prepared a functional rat LDL receptor minigene construct that can produce mRNA after splicing. Sequence analysis suggests that this construct has the potential to code for a truncated version of LDL receptor protein. This minigene could be used as a research tool to identify small molecules, natural products, and regulators of the LDL receptor gene that could be developed into LDL receptor-specific activators for therapeutic use.


Current status of prosthetic cardiac valves.
The majority of patients with acquired valvular heart disease have severe damage to valves which is not amenable to repair but can now be treated by valve replacement with an acceptable mortality and morbidity. The caged ball or disc valve is widely used and is proving clinically satisfactory for cardiac valve replacement. Thromboembolism is the significant complication. With improvement in technique the incidence of infection, detachment and other complications has been reduced.


Twelve tips for teaching the informed consent conversation.
Obtaining informed consent has been traditionally viewed as a mundane task, learned on the job and often relegated to an inexperienced member of the healthcare team. In reality, the process of obtaining informed consent is complex, challenging, and warrants focused teaching, observation and feedback. There are few published standards for what should be included in a high-quality informed consent conversation, and little or no guidance regarding how to best teach the process of conducting this type of shared decision-making conversation. The following twelve tips provide a roadmap for teaching the essential components of how to obtain informed consent, including both content and communication skills, with a focus on common pitfalls for trainees, and strategies to address them.