Anatomical endoscopic retrograde cholangiopancreatography simulator using moulded meshed silicone: A novel simulator pilot study.
Endoscopic retrograde cholangio-pancreatography (ERCP) has higher rates of morbidity and mortality compared to upper or lower gastrointestinal tract endoscopy. The availability of magnetic resonance cholangiopancreatography means ERCP is usually performed for therapeutic purposes. Simulation could provide an adjunct to patient-based training in ERCP however models to date have been unconvincing. This ERCP simulation model was constructed from moulded meshed silicone by co-designers: Jean Wong and Kai Cheng. The anatomical orientation was based on a combination of anatomical specimens, sectional atlases, and the clinical experience of expert endoscopists. From March to October 2022, we recruited 5 surgeons/gastroenterologists to the expert group and 14 medical students, junior doctors, or surgical/gastroenterological trainees to the novice group. Most experts either agreed or strongly agreed that the simulation anatomy appearance (100%), anatomical orientation (83%), tactile feedback (66%), traversal actions (67%), cannula positioning (66%) and papilla cannulation (67%) resembled the procedure in humans. Experts statistically significantly outperformed novices in obtaining a cannulating position (80% vs. 14%, P = 0.006) and successful papilla cannulation (80% vs. 7%, P = 0.0015) on their first attempt. The novice group had statistically significant improvements in time to obtaining a cannulating position (3.53 vs. 11.5 min, P = 0.006) and passing the duodenoscope to the papilla (2.55 vs. 4 passes, P = 0.009). The simulator showed statistically significant results in face, content, and construct validity. A follow-up validation study should recruit participants across multiple institutions. External validity could be assessed by comparing expert proceduralist simulator performance against clinical ERCP performance.


[Effect of the vestibular nuclei of the medulla oblongata on the serotoninergic system function of the brain and small intestine in the rat].
In alert adult female Wistar albino rats, high-frequency stimulation of the Deiters' nuclei with biphasic square pulses via implanted electrodes evoked a significant increase in the serotonin (5-HT) content in the cerebellum, hypothalamus and hippocampus, and a decrease in the striatum with a parallel increase of 5- hydroxiindolacetic acid (5-HIAA) level in the cerebellum, thalamus and spinal cord and its decrease in the parietal cortex. Destruction of the vestibular nuclei, conversely, produced a decrease in the 5-HT content in the hypothalamus, medulla oblongata and spinal cord, as well as 5-HIAA in the thalamus and did not affect the contents of these substances in other areas of the CNS. In contrast to the brain, the duodenum and ileum revealed no considerable changes in the 5-HT or 5-HIAA contents under both influences.


Transthoracic exposure for anterior spinal surgery.
The anterior approach to the vertebral column is used to treat fractures, spinal deformities, and destructive lesions secondary to tumor or infection. The thoracic surgeon, working with orthopedic surgeons and neurosurgeons, is uniquely qualified to provide surgical exposure expediently and assist in postoperative care. Forty-five patients with spinal deformities secondary to trauma (18 patients), congenital anomalies (16 patients), neoplastic disease (7 patients), and inflammation (4 patients) were treated by a transthoracic (37 patients) or thoracoabdominal (10 patients) anterior approach to the vertebral column. Two patients had subsequent operations. Free and vascularized rib grafts were used for stabilization and fusion with good results and few complications (8 patients). These results indicate that interspecialty cooperation results in expedient surgical exposure and good postoperative care.


Oral administration of prednisone to control refractory vertigo in Ménière's disease: a pilot study.
To establish whether the oral administration of moderate doses of prednisone reduces refractory vertigo in Ménière's disease. Blinded, randomized, controlled trial. Tertiary referral center. Patients with Ménière's disease with limited vertigo control (Class C) and severe disability (Scale 3). Two groups (n = 8 per group) were treated orally with either diphenidol (25 mg/d) plus acetazolamide (250 mg/48 h) (control group), or the same treatment plus prednisone (0.35 mg/kg) daily for 18 weeks (prednisone group). The variables evaluated were the frequency and duration of vertigo, tinnitus, aural fullness, and audiographic parameters. The clinical surveillance was performed for 12 months after prednisone withdrawal. The frequency and duration of vertigo episodes were reduced by 50% and 30%, respectively, by prednisone treatment. Prednisone-treated patients manifested a significant reduction in tinnitus. No changes were observed in aural fullness or hearing. No metabolic or infectious disorders were observed. Oral prednisone helps to control refractory vertigo in Ménière's disease. These preliminary data suggest that prednisone can be a good noninvasive antivertigo management regimen for these patients.


Photodynamic therapy in skin rejuvenation.
Photodynamic therapy is a noninvasive technique used in the treatment of various skin disorders. This article will provide readers with an extensive review of the popular chosen topical photosensitizers, varied used light sources and lasers, and medical and cosmetic indications treated with photodynamic therapy.


Kawasaki disease and hepatobiliary involvement: report of two cases.
Kawasaki disease (KD) without affection of the coronary artery system is rare. Optic nerve pathology together with KD has not been described earlier. We present one case of KD in a 12-year-old girl predominantly with prolonged cholestasis, and a second case of multiple recurrent KD in a 9-year-old boy with hepatomegaly and ischemic optic nerve neuropathy. The coronary artery system was not involved in either case. KD warrants rapid diagnosis and immediate specific treatment in order to prevent the high risk of coronary artery aneurysm and stenosis.


Moving molecular targeted drug therapy towards personalized medicine: issues related to clinical trial design.
With the event of new Molecular targets, clinical trial design requirements to perform these trials are changing. This paper discusses some of the considerations that need to be taken into account when designing a trial, including those trials that assess combinations of targets.


Corrigendum: Candidate Gene Resequencing in a Large Bicuspid Aortic Valve-Associated Thoracic Aortic Aneurysm Cohort: SMAD6 as an Important Contributor.
[This corrects the article on p. 400 in vol. 8, PMID: 28659821.].


Combination of α-Tomatine and Curcumin Inhibits Growth and Induces Apoptosis in Human Prostate Cancer Cells.
α-Tomatine is a glycoalkaloid found in tomatoes and curcumin is a major yellow pigment of turmeric. In the present study, the combined effect of these two compounds on prostate cancer cells was studied. Treatment of different prostate cancer cells with curcumin or α-tomatine alone resulted in growth inhibition and apoptosis in a concentration-dependent manner. Combinations of α-tomatine and curcumin synergistically inhibited the growth and induced apoptosis in prostate cancer PC-3 cells. Effects of the α-tomatine and curcumin combination were associated with synergistic inhibition of NF-κB activity and a potent decrease in the expression of its downstream gene Bcl-2 in the cells. Moreover, strong decreases in the levels of phospho-Akt and phosphor-ERK1/2 were found in PC-3 cells treated with α-tomatine and curcumin in combination. In animal experiment, SCID mice with PC-3 xenograft tumors were treated with α-tomatine and curcumin. Combination of α-tomatine and curcumin more potently inhibited the growth of PC-3 tumors than either agent alone. Results from the present study indicate that α-tomatine in combination with curcumin may be an effective strategy for inhibiting the growth of prostate cancer.


Effects of heterozygosity on performance of purebred and crossbred pigs.
In pigs, crossbreeding aims at exploiting heterosis, but heterosis is difficult to quantify. Heterozygosity at genetic markers is easier to measure and could potentially be used as an indicator of heterosis. The objective of this study was to investigate the effect of heterozygosity on various maternal and production traits in purebred and crossbred pigs. The proportion of heterozygosity at genetic markers across the genome for each individual was included in the prediction model as a fixed regression across or within breeds. Estimates of regression coefficients of heterozygosity showed large effects for some traits. For maternal traits, regression coefficient estimates were always in a favourable direction, while for production, meat and slaughter quality traits, they were both favourable and unfavourable. Traits with the largest estimated effects of heterozygosity were total number born, litter weight at 3 weeks, weight at 150 days, and age at 40 kg. Estimates of regression coefficients on heterozygosity differed between breeds. Traits with the largest effect of heterozygosity also showed a significant (P < 0.05) increase in prediction accuracy when heterozygosity was included in the model compared to the model without heterozygosity. For traits with the largest estimates of regression coefficients on heterozygosity, the inclusion of heterozygosity in the model improved prediction accuracy. Using models that include heterozygosity would result in selecting different animals for breeding, which has the potential to improve genetic gain for these traits. This is most beneficial when crossbreds or several breeds are included in the estimation of breeding values and is relevant to all species, not only pigs. Thus, our results show that including heterozygosity in the model is beneficial for some traits, likely due to dominant gene action.


Estimation of Gas Holdup Using the Gassed to Ungassed Power Ratio of an Oxygen-Water System in a Stirred and Sparged Tank Contactor.
Gas holdup (εg) and power correlations in gas-liquid (G-L) systems, apart from the physicochemical properties of the liquid phase, are dependent on impeller-sparger-vessel geometry. To date, reported correlations do not specifically address this issue, and it must be investigated with a unified approach. Here, we propose a correlation via the use of a normalized εg that involves the impeller-sparger system geometry for a vessel of standard geometry expressed as a function of an easily measurable and independent operational parameter, that is, (1 - P g/P l), where P g/P l is the gassed to ungassed power ratio. Furthermore, our work demonstrates that P g/P l can be used as a tool for the identification of hydrodynamic regimes. Radial and axial impellers with ring spargers were used in a stirred and sparged contactor (SSTC) of 0.25 m diameter containing 1 × 10-2 m3 water. The oxygen flowrate (Q g) was varied from 2.5 to 40 LPM or (4.17 to 66.7) × 10-5 m3 s-1, and the agitation intensity (N 0) was varied from 1.67 to 50 rps at the temperature (θ) = 313 K under atmospheric pressure. This novel correlation is easy to use, offers reasonable precision, and can serve as a valuable alternative to more complex correlation models.


Solving Fredholm Integral Equations Using Deep Learning.
The aim of this paper is to provide a deep learning based method that can solve high-dimensional Fredholm integral equations. A deep residual neural network is constructed at a fixed number of collocation points selected randomly in the integration domain. The loss function of the deep residual neural network is defined as a linear least-square problem using the integral equation at the collocation points in the training set. The training iteration is done for the same set of parameters for different training sets. The numerical experiments show that the deep learning method is efficient with a moderate generalization error at all points. And the computational cost does not suffer from "curse of dimensionality" problem.


Phytochemicals in Morinda citrifolia fruit selectively modulate age-associated immunity and antioxidant enzyme activities through ERK pathway in splenic lymphocytes of male F344 rats.
The mechanisms of immunomodulatory effects of Morinda citrifolia (Noni) were examined through intracellular signaling pathways in the splenocytes and their modulation by phytochemicals using bioinformatics tools. Noni fruit juices without seeds (NSL) and with seeds (NWS) were co-incubated in vitro with splenocytes from young, middle-aged and old F344 male rats and proliferation of lymphocytes, cytokine production, antioxidant enzyme activities and intracellular signaling markers were measured. NSL decreased lymphoproliferation in early middle-aged rats, and IL-2 and IFN-γ production in old rats. In contrast, NWS enhanced lymphoproliferation in young and old rats, IL-2 and IFN-γ production in middle-aged and old rats. The activities of antioxidant enzymes were augmented by NWS and NSL in old rats. NWS reversed age-related increase in lipid peroxidation in all age-groups, while NSL increased lipid peroxidation in old rats. NSL increased p-ERK in old rats and decreased p-CREB in young and middle-aged rats. In contrast, NWS decreased p-ERK in all age groups and increased p-CREB in old rats. Both NSL and NWS increased p-Akt expression in middle-aged and old rats. Both NSL and NWS suppressed p-NF-κB expression in middle-aged and old rats. Docking studies demonstrated that Noni phytochemicals, damnacanthal, myricetin and ursolic acid, are potent inhibitors of ERK with binding sites in the catalytic and phosphorylation sites of the molecule. These results suggest that Noni fruit juices with or without seeds modulate cell-mediated immunity and antioxidant enzyme activities based on the phytochemicals that may differentially influence cell signaling and therefore, age-associated immunity.


Surgical correction of bifid nose.
Evaluation of the aesthetic outcome and functional aspect after surgical correction of bifid nose by combined Millard forked flap with external rhinoplasty Bifid nose is a rare congenital anomaly that results during facial development but the explicit mechanism is not clearly understood. Clinical findings are quite variable with a wide range of severity. Surgical correction still represents great challenge to facial plastic surgeons; extensive deformities in many cases, rarity of condition and paucity of publications are contributing factors. Surgical correction of six patients with bifid nose by a combined Millard forked flap with external rhinoplasty The aesthetic and functional outcomes were acceptable for all patients and parents. There were no considerable postoperative complications. This approach is highly effective for various grades of bifid nose. Early management is preferable to avoid psychological morbidity. Secondary rhinoplasty is usually needed for cosmetic refinement.


Glycan-based biomarkers for mucopolysaccharidoses.
The mucopolysaccharidoses (MPS) result from attenuation or loss of enzyme activities required for lysosomal degradation of the glycosaminoglycans, hyaluronan, heparan sulfate, chondroitin/dermatan sulfate, and keratan sulfate. This review provides a summary of glycan biomarkers that have been used to characterize animal models of MPS, for diagnosis of patients, and for monitoring therapy based on hematopoietic stem cell transplantation and enzyme replacement therapy. Recent advances have focused on the non-reducing terminus of the glycosaminoglycans that accumulate as biomarkers, using a combination of enzymatic digestion with bacterial enzymes followed by quantitative liquid chromatography/mass spectrometry. These new methods provide a simple, rapid diagnostic strategy that can be applied to samples of urine, blood, cerebrospinal fluid, cultured cells and dried blood spots from newborn infants. Analysis of the non-reducing end glycans provides a method for monitoring enzyme replacement and substrate reduction therapies and serves as a discovery tool for uncovering novel biomarkers and new forms of mucopolysaccharidoses.


Short-term toxicity of 2-phenylpropan-1-ol (hydratropic alcohol) in rats.
Phenylpropan-1-ol was added to the diet of groups of 15 male and 15 female rats to provide intakes of 0 (control), 10, 40 or 160 mg/kg/day for 13 wk. No effects on body weight, food intake, water intake, haematology, semi-quantitative analysis of urine, renal concentration and dilution tests, serum chemistry or the histological examination could be attributed to treatment. Increased liver weights at the highest dose level in both sexes and increased kidney weights at the two highest dose levels in males were considered to be related to treatment, but in view of the lack of histological abnormalities this study did not demonstrate whether these were toxic or adaptive effects. An isolated renal mesenchymal tumour was found in the females fed the highest dose level. It is concluded that the no-effect level in this study was 10 mg/kg/day.


Using neuroblastoma cell lines to address differential specificity to organophosphates.
1. Organophosphates can cause acute toxicity, which follows inhibition of acetylcholinesterase (AChE), or delayed neuropathy, which follows inhibition of neuropathy target esterase (NTE). 2. Human neuroblastoma SH-SY5Y cells contain AChE and NTE. 3. Organophosphates actively able to inhibit AChE in animal models inhibited AChE in neuroblastoma cells. 4. Inhibition of NTE in neuroblastoma cells could identify active organophosphates capable of causing delayed neuropathy in animal models and distinguish these organophosphates from those that do not cause delayed neuropathy in animal models.


Immunocytochemical detection of GABAergic nerve cells in the human temporal cortex using a direct gamma-aminobutyric acid antiserum.
Recently, an immunocytochemical method using glutaraldehyde fixation and an antiserum developed against a GABA--glutaraldehyde--protein conjugate has permitted direct visualization of GABAergic structures in the brains of perfused animals. This paper reports a successful use of this technique on human temporal cortex fixed by immersion. The cerebral tissue was obtained from patients operated for focal epilepsy. GABA-positive somata, fibres and terminals are observed in all layers of the temporal cortex. Terminals are particularly abundant in the superficial portion of layer I and in layers II, III and IV. Dense plexuses of fibres are located in layers II, III, IV and VI and in the underlying white matter. Somata are found in all cortical layers and in the underlying white matter; they are round, oval, fusiform or triangular and exhibit a multipolar, bitufted or bipolar dendritic pattern. This technique for the visualization of GABAergic structures in the human brain may allow a better understanding of the pathogeny of epilepsy in which the GABAergic transmission has been implicated.


Chemical characteristics, evolution, and quality of groundwater and processes controlling its fluoride concentration features: case study of a typical high-fluoride areas in the Southwestern Shandong Plain, China.
In this study, the groundwater (GW) in the high-fluorine area of the Southwestern Shandong Plain was divided according to the characteristics of high Na% (> 75%), and its water chemistry characteristics and causes were discussed separately, and the hydrochemical process of the formation of high-fluorine GW was determined. Finally, the GW quality of the study area was evaluated. The results proved that silicate hydrolysis can significantly promote the release of F- in fluorine-containing minerals; high %Na can be used as one of the early-warning conditions for judging high-fluoride areas. To this end, 132 GW samples were collected from 66 wells during the dry and wet seasons. The study area was found to have weakly alkaline GW (pH 7.1-8.9) and could be divided into high %Na areas (HNA) and non-HNA. GW exhibited different hydrochemical characteristics between HNA and non-HNA. In non-HNA, total hardness (TH) exceeded 200 mg/L, and total dissolved solids (TDS) ranged from 514.1 to 5246.1 mg/L; in HNA, TH was less than 200 mg/L, TDS ranged from 552.8 to 1298.3 mg/L, and Na+ increased with TDS, whereas Ca2+ and Mg2+ contents were low. The main water type in HNA was HCO3-Na and in non-HNA was SO4·Cl-Ca·Mg and SO4·Cl-Na. The study area is experiencing serious fluoride pollution. GW in HNA is mostly controlled by carbonate and silicate hydrolysis and evaporation, whereas GW in non-HNA is controlled by dolomite dissolution and cation exchange in the main. Moreover, GW in HNA has significantly been altered by albite hydrolysis, which produces Na+ and HCO3- and triggers various reactions promoting the release of F- from fluorine-containing minerals (FCM). Regarding the water quality for irrigation, GW in HNA was found to be less suitable than that in non-HNA. Nevertheless, in terms of the water quality index (WQI), GW is moderate for drinking and poor for irrigation. Therefore, extensive attention should be paid to the exploitation and management of high-sodium GW in the plain area.


Hormonal regulation of anthocyanin biosynthesis for improved stress tolerance in plants.
Due to unprecedented climate change, rapid industrialization and increasing use of agrochemicals, abiotic stress, such as drought, low temperature, high salinity and heavy metal pollution, has become an increasingly serious problem in global agriculture. Anthocyanins, an important plant pigment, are synthesized through the phenylpropanoid pathway and have a variety of physiological and ecological functions, providing multifunctional and effective protection for plants under stress. Foliar anthocyanin accumulation often occurs under abiotic stress including high light, cold, drought, salinity, nutrient deficiency and heavy metal stress, causing leaf reddening or purpling in many plant species. Anthocyanins are used as sunscreens and antioxidants to scavenge reactive oxygen species (ROS), as metal(loid) chelators to mitigate heavy metal stress, and as crucial molecules with a role in delaying leaf senescence. In addition to environmental factors, anthocyanin synthesis is affected by various endogenous factors. Plant hormones such as abscisic acid, jasmonic acid, ethylene and gibberellin have been shown to be involved in regulating anthocyanin synthesis either positively or negatively. Particularly when plants are under abiotic stress, several plant hormones can induce foliar anthocyanin synthesis to enhance plant stress resistance. In this review, we revisit the role of plant hormones in anthocyanin biosynthesis and the mechanism of plant hormone-mediated anthocyanin accumulation and abiotic stress tolerance. We conclude that enhancing anthocyanin content with plant hormones could be a prospective management strategy for improving plant stress resistance, but extensive further research is essentially needed to provide future guidance for practical crop production.


Contrast Agents for MR Imaging.
Contrast media are essential to the practice of MR imaging. An increasing variety of agents have been approved for clinical use, specific contrast agents can often be tailored to a specific clinical question. Compared with CT contrast media, MR imaging contrast is well tolerated with an excellent safety record and a low incidence of adverse events. In this article, we review the pharmacology, indications, and the common adverse events of the intravenous and oral MR contrast agents most commonly used in contemporary imaging practice, including gadolinium-based contrast, manganese and iron-based agents and the most common oral contrast agents.


Identification of two types of smooth muscle myosin heavy chain isoforms by cDNA cloning and immunoblot analysis.
We previously reported the characterization of a rabbit uterus cDNA clone (SMHC29) which encoded part of the light meromyosin of smooth muscle myosin heavy chain (Nagai, R., Larson, D.M., and Periasamy, M. (1988) Proc. Natl. Acad. Sci. U. S. A. 85, 1047-1051). We have now characterized a second cDNA clone (SMHC40) which also encodes part of the light meromyosin but differs from SMHC29 in the following respects. Nucleotide sequence analysis demonstrates that the two myosin heavy chain mRNAs are identical over 1424 nucleotides but differ in part of the 3'-carboxyl coding region and a portion of the 3'-nontranslated sequence. Specifically, SMHC40 cDNA encodes a unique stretch of 43 amino acids at the carboxyl terminus, whereas SMHC29 cDNA contains a shorter carboxyl terminus of 9 unique amino acids which is the result of a 39-nucleotide insertion. Recent peptide mapping of smooth muscle myosin heavy chain identified two isotypes with differences in the light meromyosin fragment that were designated as SM1 (204 kDa) and SM2 (200 kDa) type myosin (Eddinger, T. J., and Murphy, R.A. (1988) Biochemistry 27, 3807-3811). In this study we present direct evidence that SMHC40 and SMHC29 mRNA encode the two smooth muscle myosin heavy chain isoforms, SM1 and SM2, respectively, by immunoblot analysis using antibodies against specific carboxyl terminus sequences deduced from SMHC40 and SMHC29 cDNA clones.


The presence of clusters of plasmacytoid dendritic cells is a helpful feature for differentiating lupus panniculitis from subcutaneous panniculitis-like T-cell lymphoma.
Both lupus panniculitis (LP) and subcutaneous panniculitis-like T-cell lymphoma (SPTCL) are characterized by subcutaneous lobular lymphocytic infiltrates, and they are sometimes difficult to differentiate. Recently, plasmacytoid dendritic cells (PDCs) were found to be present in various types of cutaneous lupus erythematosus lesions, including LP, and are supposed to play important pathogenetic roles. The aim of this study was to investigate whether PDCs are differentially present in these two diseases and can be utilized to differentiate them. Conventional histopathological features were also compared. Initial biopsies from 21 LP and 11 SPTCL patients were analysed. Our results showed that the presence of lymphoid follicles, dermal mucin deposition and lack of moderate to marked nuclear atypia or adipocyte rimming were more suggestive of LP. Several distinct patterns of fat necrosis, i.e. hyaline/lipomembranous and fibrinoid/coagulative in LP and SPTCL, respectively, were also diagnostically useful. Also, clusters of PDCs were characteristically seen in LP lesions (17/21, 81%) but not in SPTCL lesions (2/11, 18.2%). In LP lesions, but not in SPTCL lesions, the presence of epidermal interface change correlated perfectly with the presence of PDCs in the papillary dermis. We conclude that the presence of clusters of PDCs and certain histological features are helpful for the differential diagnosis.


Response of Vallisneria natans to aluminum phytotoxicity and their synergistic effect on nitrogen, phosphorus change in sediments.
Increasing aluminum (Al) use and its effects on aquatic systems have been a global issue, however the Al impacts on submerged plants and their ecological functions were poorly understood. Aquatic simulation experiments were performed to study Al-toxicity on the germination and seedling morphological and physiological characteristics of Vallisneria natans, and investigate their synergistic effect on nitrogen (N), phosphorus (P) change and microbial community in sediment. The seeds germination characteristics, growth and physiological parameters of seedlings, including root activity, were significantly affected by alum treatments and the inhibition levels increased with Al3+ concentration. The Al accumulation in roots and leaves were significantly different. Al3+ concentration above 0.3 mg/L showed toxic to V. natans. TN, TP, IP, Fe/Al-P contents in sediments varied markedly under co-existence of Al and V. natans. Additionally, the relative abundance of sediment microbial community related to N, P cycle was effected. Results concluded that the increasing aquatic Al-concentration inhibits growth and propagation of submerged plants and the ecological restoration effect, and exerts synergistic effect with submerged plants on N, P components in sediments. Such findings were helpful for Al ecological evaluation, and were instructive for the submerged plants restoration in shallow eutrophic lakes with Al input.


Carbohydrate-induced modulation of cell membrane. VIII. Agglutination with mammalian lectin galectin-1 increases osmofragility and membrane fluidity of trypsinized erythrocytes.
Interaction of lectins with cell surface determinants may alter membrane properties. Using trypsinized rabbit erythrocytes as model we tested the capacity of an endogenous lectin in this respect. Galectin-1 is a member of an adhesion/growth-regulatory family known to interact for example with ganglioside GM(1) and also the hydrophobic tail of oncogenic H-Ras. Assays on membrane fluidity and osmofragility detect galectin-1's capacity to increase the parameters. Moreover, it increases susceptibility of erythrocytes to radical damage. These observations indicate the potential of this endogenous lectin to affect membrane properties beyond the immediate interaction with cell surface epitopes.


The looming maladaptive style in social anxiety.
This exploratory study examined the relationship between the looming maladaptive style (i.e., an enduring and traitlike cognitive pattern to appraise threat as rapidly rising in risk, progressively worsening, or actively speeding up and accelerating) and three different aspects of trait social anxiety (i.e., fear of negative evaluation, social interaction anxiety, and public scrutiny fears) as well as general anxiety and depression. A large nonclinical, female-only sample (n=152) completed the Looming Maladaptive Style Questionnaire-II (Riskind, J. H., Williams, N. L., Theodore, L. G., Chrosniak, L. D., & Cortina, J. M. (2000). The looming maladaptive style: Anxiety, danger, and schematic processing. Journal of Personality and Social Psychology, 79, 837-852), which assesses two types of looming vulnerability: social (i.e., looming appraisals in response to potentially threatening social situations) and physical (i.e., looming appraisals in response to potentially threatening physical stimuli). Multiple regression analyses indicated that social looming uniquely predicted fear of negative evaluation, social interaction anxiety, and public scrutiny fears, accounting for 7%, 4%, and 3% of the variance, respectively. However, social looming did not predict depression. These findings support the looming model of anxiety and encourage further attention to the possible role of social looming as an anxiety-specific vulnerability factor in social anxiety.


IRT1 and ZIP2 were involved in exogenous hydrogen-rich water-reduced cadmium accumulation in Brassica chinensis and Arabidopsis thaliana.
The results of Cd (cadmium) concentration, Cd2+ fluorescent staining, NMT (non-invasive micro-test technology) analysis of Cd absorption revealed the remarkably positive role of HRW in reducing Cd uptake by root of pak choi seedlings. BcIRT1 (iron-regulated transporter 1) and BcZIP2 (zinc-regulated transporter protein 2) are the main Cd transporters in pak choi, but their roles in the process of HRW-reduced Cd uptake is still far from being answered. In this study, we specifically verified the function of IRT1 and ZIP2 in HRW-reduced Cd absorption in pak choi and Arabidopsis thaliana. Heterologous and homologous expression in Arabidopsis thaliana displayed that Cd concentrations in wild-type (Col-0) and transgenic A. thaliana of IRT1 and ZIP2 were significantly reduced by HRW, except for irt1- and zip2-mutant. NMT detection showed that HRW not only decreased Cd2+ influx in root of WT and transgenic lines, but also enhanced the competition between Zn and Cd. Taken together, the HRW-induced reduction of Cd accumulation in plants may be result from depressing the expression of BcIRT1 and BcZIP2 and affecting the preference of BcIRT1 and BcZIP2 in ion uptake.


Hepatitis B and Schistosoma co-infection in a non-endemic area.
Schistosomiasis is related to the development of liver fibrosis and portal hypertension. Chronic co-infection with HBV and Schistosoma has been associated in endemic areas with a higher risk for a more severe liver disease. However, no studies have assessed the real importance of this co-infection in non-endemic regions. This is a retrospective observational study of Sub-Saharan immigrants attending between October 2004 and February 2014. Patients with chronic HBV infection with and without evidence of schistosomal infection were compared. Epidemiological, analytical, and microbiological data were analysed. Likelihood of liver fibrosis based on APRI and FIB-4 indexes was established. A total of 507 patients were included in the study, 170 (33.5 %) of them harbouring evidence of schistosome infection. No differences were found in transaminase, GGT, and ALP levels. In fibrosis tests, a higher proportion of patients with HVB and S. mansoni detection reached possible fibrosis scores (F > 2) when compared to patients without schistosomiasis: 17.4 vs 14.2 % and 4.3 % vs 4.2 % (using high sensitivity and high specificity cut-offs respectively), although differences were not statistically significant (p = 0.69, p = 0.96). For possible cirrhosis (F4) score, similar results were observed: 4.3 % of co-infected patients vs 2.1 % of mono-infected ones, p = 0.46. According to these datas, in non-endemic regions the degree of hepatic fibrosis in patients with chronic hepatitis B is not substantially modified by schistosome co-infection.


Mechanisms and management of edema in pediatric nephrotic syndrome.
Edema is the abnormal accumulation of fluid in the interstitial compartment of tissues within the body. In nephrotic syndrome, edema is often seen in dependent areas such as the legs, but it can progress to cause significant accumulation in other areas leading to pulmonary edema, ascites, and/or anasarca. In this review, we focus on mechanisms and management of edema in children with nephrotic syndrome. We review the common mechanisms of edema, its burden in pediatric patients, and then present our approach and algorithm for management of edema in pediatric patients. The extensive body of experience accumulated over the last 5 decades means that there are many options, and clinicians may choose among these options based on their experience and careful monitoring of responses in individual patients.


[Long-term low-dose microcystin-LR exposure induces renal injury in mice by activating PI3K/AKT signaling pathway].
To investigate the toxic effect of long-term low-dose exposure to microcystin-LR (MC-LR) on kidney and its underlying molecular mechanism. Forty male C57BL/6 mice were randomized into 4 groups for exposure to 0, 1, 60, and 120 μg/L MC-LR (mixed in drinking water) for 12 months, and the body and kidney weight changes and renal pathologies of the mice were observed. The renal function indexes, the mRNA expression levels of IL-6, TNF-α and IL-10, and relative expression levels of PI3K/AKT pathway proteins in the kidney of the mice were detected. These parameters were also detected in HEK293 cells treated with MC- LR, LY294002, or both. The overall trend of body weight changes was consistent among the 4 groups of mice, and their kidney mass and kidney index underwent no significant changes. In mice exposed to 60 and 120 μg/L MC-LR, obvious renal structural damage and significant elevation of the BUN and SCr levels were observed (P < 0.05) with up-regulated levels of IL-6 and TNF-α mRNA and increased protein expressions of p-PI3K/PI3K and p-AKT/AKT in the renal tissues (P < 0.05). IL-10 mRNA expression was significantly decreased in all the exposure groups (P < 0.05). The levels of BUN and Cr increased significantly in MC-LR-treated HEK293 cells and decreased in cells treated with both MC-LR and LY294002 (P < 0.05). The mRNA expression levels of IL-6 and TNF-α increased and the level of IL-10 mRNA decreased obviously in MC-LR-treated cells, and the opposite changes were observed in the cells with the combined treatment (P < 0.05). The proteins levels of p-PI3K/PI3K and p-AKT/AKT were significantly up-regulated in MC-LR group and down-regulated in the combined treatment group (P < 0.05). MC- LR can activate inflammatory response and induce renal structural and functional damages in mice by activating the PI3K/AKT signaling pathway.


The development of an analytical method for urinary metabolites of the riot control agent 2-chlorobenzylidene malononitrile (CS).
The analysis of biomedical samples such as urine and blood can provide evidence of exposure to chemicals for a range of applications including occupational exposure monitoring, detection of drugs of abuse, performance enhancement in sport and investigations of poisoning and incapacitation. This paper reports the development of an analytical method for two suspected urinary metabolites of the riot control agent 2-chlorobenzylidene malononitrile (CS): 2-chlorohippuric acid and 2-chlorobenzyl-N-acetylcysteine. 2-Chlorohippuric acid was identified in all 2h post-exposure samples from a set of urine samples taken from army recruits exposed to low levels of thermally dispersed CS during training. 2-Chlorobenzyl-N-acetylcysteine, a metabolite known to be formed in the rat, was not identified in any of the samples. The lower limit of detection (LLOD) for 2-chlorohippuric acid and 2-chlorobenzyl-N-acetylcysteine was 1ng/ml and 0.5ng/ml in pooled urine from the pre-exposed subjects. 2-Chlorohippuric acid was rapidly excreted but was detectable in the urine of 17 of the 19 subjects tested 20h after exposure.


An automated assay for adenylate cyclase using reversed-phase high-performance liquid chromatography.
An automated high-performance liquid chromatographic method for the assay of 3',5'-cyclic AMP was developed using octylsilica. Total analysis time was 10.1 min, with cAMP eluting at 3 min. As little as 10 pmol of cyclic AMP could be detected by absorption at 260 nm. Peak height and area were linearly related to cyclic AMP concentration over at least two orders of magnitude. The analytical procedure gave good results in the assay of crude microsomal preparations of adenylate cyclase from both bovine brain and sea urchin eggs. The method was used to demonstrate that sea urchin adenylate cyclase is a Ca2+-activated enzyme.


Foam Cells: One Size Doesn't Fit All.
Chronic inflammation in many infectious and metabolic diseases, and some cancers, is accompanied by the presence of foam cells. These cells form when the intracellular lipid content of macrophages exceeds their capacity to maintain lipid homeostasis. Concurrently, critical macrophage immune functions are diminished. Current paradigms of foam cell formation derive from studies of atherosclerosis. However, recent studies indicate that the mechanisms of foam cell biogenesis during tuberculosis differ from those operating during atherogenesis. Here, we review how foam cell formation and function vary with disease context. Since foam cells are therapeutic targets in atherosclerosis, further research on the disease-specific mechanisms of foam cell biogenesis and function is needed to explore the therapeutic consequences of targeting these cells in other diseases.


Development of the epidermal growth factor receptor inhibitor Tarceva (OSI-774).
The epidermal growth factor receptor (EGFR) is a transmembrane receptor involved in the regulation of a complex array of essential biological processes such as cell proliferation and survival. Dysregulation of EGFR signaling network has been frequently reported in multiple human cancers and has been associated with the processes of tumor development, growth, proliferation, metastasis and angiogenesis. Inhibition of the EGFR was associated with antitumor effects in preclinical models. On the bases of these data, therapeutics targeting the EGFR were explore in clinical trials. Tarceva (OSI-774, OSI Pharmaceuticals, Uniondale, NY) is a small molecule selective inhibitor of the EGFR tyrosine kinase (TK). In preclinical studies, Tarceva inhibited the phosphorylation of the EGFR in a dose and concentration dependent manner resulting in cell cycle arrest and induction of apoptosis. In in vivo studies, the agent caused tumor growth inhibition and shoved synergistic effects when combined with conventional chemotherapy. Subsequent single agent phase I studies and phase I studies in combination with chemotherapy demonstrated that the agent has a good safety profile and induced tumor growth inhibition in a substantial number of patients with a variety of different solid tumor. Preliminary report from phase II studies confirmed the excellent tolerability of Tarceva as well as showed encouraging preliminary activity. Phase III studies have either been completed or are ongoing in several tumor types such as lung cancer and pancreatic cancer. In summary, Tarceva is a novel inhibitor of the EGFR TK which has shown promising activity in initial studies and is currently undergoing full development as an anticancer drug.


External validation and revision of Penn incisional hernia prediction model: A large-scale retrospective cohort of abdominal operations.
Incisional hernia (IH) manifests in 10%-15% of abdominal surgeries and patients at elevated risk of this complication should be identified for prophylactic intervention. This study aimed to externally validate the Penn hernia risk calculator. The Ramathibodi abdominal surgery cohort was constructed by linking relevant hospital databases from 2010 to 2021. Penn hernia risk scores were calculated according to the original model which was externally validated using a seven-step approach. An updated model which included four additional predictor variables (i.e., age, immunosuppressive medication, ostomy reversal, and transfusion) added to those of the three original predictors (i.e., body mass index, chronic liver disease, and open surgery) was also evaluated. The area under the receiver operating characteristic curve (AUC) was estimated, and calibration performance was compared using the Hosmer-Lemeshow goodness-of-fit method for the observed/expected (O/E) ratio. A total of 12,155 abdominal operations were assessed. The original Penn model yielded fair discrimination with an AUC (95% confidence interval (CI)) of 0.645 (0.607, 0.683). The updated model that included the additional predictor variables achieved an acceptable AUC (95% CI) of 0.733 (0.698, 0.768) with the O/E ratio of 0.968 (0.848, 1.088). The updated model achieved improved discrimination and calibration performance, and should be considered for the identification of high-risk patients for further hernia prevention strategy.


Activation of single heteromeric GABA(A) receptor ion channels by full and partial agonists.
The linkage between agonist binding and the activation of a GABA(A) receptor ion channel is yet to be resolved. This aspect was examined on human recombinant alpha1beta2gamma2S GABA(A) receptors expressed in human embryonic kidney cells using the following series of receptor agonists: GABA, isoguvacine, 4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol (THIP), isonipecotic acid, piperidine-4-sulphonic acid (P4S), imidazole-4-acetic acid (IAA), 5-(4-piperidyl)-3-isothiazolol (thio-4-PIOL) and 5-(4-piperidyl)-3-isoxazolol (4-PIOL). Whole-cell concentration-response curves enabled the agonists to be categorized into four classes based upon their maximum responses. Single channel analyses revealed that the channel conductance of 25-27 pS was unaffected by the agonists. However, two open states were resolved from the open period distributions with mean open times reduced 5-fold by the weakest partial agonists. Using saturating agonist concentrations, estimates of the channel shutting rate, alpha, ranged from 200 to 600 s(-1). The shut period distributions were described by three or four components and for the weakest partial agonists, the interburst shut periods increased whilst the mean burst durations and longest burst lengths were reduced relative to the full agonists. From the burst analyses, the opening rates for channel activation, beta, and the total dissociation rates, k(-1), for the agonists leaving the receptor were estimated. The agonist efficacies were larger for the full agonists (E approximately 7-9) compared to the weak partial agonists ( approximately 0.4-0.6). Overall, changes in agonist efficacy largely determined the different agonist profiles with contributions from the agonist affinities and the degree of receptor desensitization. From this we conclude that GABA(A) receptor activation does not occur in a switch-like manner since the agonist recognition sites are flexible, accommodating diverse agonist structures which differentially influence the opening and shutting rates of the ion channel.


Differences in soil organic carbon and soil erosion for native pasture and minimum till agricultural management systems.
There is considerable debate over how different agricultural management systems such as minimum tillage and grazing affect soil organic carbon (SOC), soil nitrogen (SN) concentrations and soil erosion over the long-term. In this study SOC, SN and erosion characteristics were compared over a ten year period for two neighbouring sites with longstanding but different land management strategies; one cropped under a minimum tillage (MT) regime and one used for grazing on largely native pasture. Both sites (Hunter Valley, New South Wales, Australia) shared the same soil type (Euchrozem) and climate. SOC and SN were both found to be ~50% higher at the grazing site while erosion was found to be significantly greater (an order of magnitude) at the cropping site despite the application of MT practices. No discernible link between erosion and either SOC, SN or C:N was evident. While both sites have temporally constant SOC, SN and C:N, the MT site offers scope for increased SOC sequestration.


Clinical comparison of two different plating methods in minimally invasive plate osteosynthesis for clavicular midshaft fractures: A randomized controlled trial.
The aim of this study was to compare the clinical and radiographic outcomes between two different plating methods (superior vs. anteroinferior) in minimally invasive plate osteosynthesis (MIPO) for acute displaced clavicular shaft fractures. A prospective, randomized controlled trial was performed in a single centre. Nineteen patients were treated with superior plating and 18 with anteroinferior plating using the MIPO technique. A 3.5-mm locking reconstruction plate was bent preoperatively and applied to either the anteroinferior or superior aspect of the clavicle through two separate incisions. The operating time, time to union, the proportional length difference, complications, and functional outcome of the shoulder joint were evaluated using the Constant score and the University of California Los Angeles (UCLA) score. There was no statistically significant difference in the Constant score and UCLA score. The mean time to union was 16.8 weeks for superior plating and 17.1 weeks for anteroinferior plating (p=0.866). The average operation time was 77.2min in superior plating and 79.4min in anteroinferior plating (p=0.491). One patient in the superior plating group showed plate failure. Despite no significant difference, one patient had nonunion in the superior plating group (p>0.999). From a clinical perspective, although MIPO with anteroinferior plating provides better outcomes especially in complications without statistically significant difference, both plating methods provided satisfactory clinical and radiographic outcomes. Level I, a single-centre, prospective, randomized controlled trial.


Autoantibodies to mitochondrial and centromere antigens in primary biliary cirrhosis and systemic sclerosis.
High levels of IgG antibodies to the multi-enzyme complex bovine pyruvate dehydrogenase (PDHC) were detected by a sensitive ELISA in all patients with histologically proven primary biliary cirrhosis (PBC), in a minority of patients with systemic sclerosis without overt PBC or with chronic liver diseases of another cause and in no rheumatoid arthritis or normal controls. Most (15/21) but not all of these positive patients recognized a 70-kD (E2) component of PDHC on immunoblotting. Additional recognition of a centromere-associated 140-kD polypeptide was associated with the presence of scleroderma-like features (Raynaud's phenomenon and sclerodactyly) in PBC, further emphasizing the serological and clinical overlap between these two conditions.


Changing prescribing behaviour: early low dose aspirin in suspected acute myocardial infarction.
Evidence obtained from large clinical trials would be of limited value, if such evidence does not reach the provider of care, and even when it reaches them, if they do not change their clinical behaviour accordingly. The aim of our study was to assess the effectiveness of intervention, aimed at changing prescribing behaviour of general practitioners (GPs) with regard to early low dose aspirin in patients with suspected acute myocardial infarction (MI). A total of 96 GPs were sent a questionnaire assessing their knowledge and practices with regard to use of low dose aspirin in acute MI in November 1995 (Q1), June 1996 (Q2) and September 1996 (Q3). An 'intervention' was carried out with a view to changing GP prescribing of low dose aspirin is suspected acute MI after the first two questionnaires were sent. The results of this study seem to show that an intensive 'intervention' achieved success in changing prescribing behaviour of GPs. Although the intervention resulted in a overall significant increase in the prescription of low dose aspirin in suspected acute MI, it was seen that in the GPs who were aged <40 years the success achieved with the 'intervention' was greater when compared with that seen in those older than 40 years. Dissemination of information on new practices in medicine are important in the process of continuing medical education for doctors. A 'personal intervention' such as is described in this study seems to have good effect.


Design, synthesis and antithrombotic evaluation of novel dabigatran prodrugs containing methyl ferulate.
A novel series of prodrugs containing dabigatran and methyl (E)-3-(4-hydroxy-2-methoxyphenyl)propenoate (methyl ferulate) were synthesized. All of them reveal the effect of thrombin-induced anti-platelet aggregation in vitro. In addition, in vivo experiment shows that one of the target compounds, X-2 (ED50=3.7 ± 1.0 μmol/kg) possesses a more potent activity for inhibiting venous thrombosis than that of dabigatran etexilate (ED50=7.8 ± 1.5 μmol/kg).


[Parodontal status distinctive features in patients with the loss of mineral density of peripheral skeleton bone tissue].
According as the loss of mineral bone density (MBD) of peripheral skeleton grows parodontal lesion heaviness increase was demonstrated. Strong negative correlations between API and PBI indices, as well as middle negative correlations between PI index and degree loss of MBD of peripheral skeleton were disclosed. In patients with osteoporosis chronic generalized parodontitis (CGP) was found more frequently when compared with patients not suffering from CGP (41,5 against 12,5% correspondingly).


Establishment and characterization of a Kaposi's sarcoma-associated herpesvirus- and Epstein-Barr virus-negative malignant lymphoma cell line (OHK) with primary effusion lymphoma immunophenotype.
A novel cell line, designated OHK, was established from ascites of a 59-year-old Japanese woman with diffuse large B-cell lymphoma showing a peculiar serosal tropism, as seen in primary effusion lymphomas (PEL). OHK exhibited a large pleomorphic morphology with irregular nuclei and distinct nucleoli, and included immunoblastic and Reed-Sternberg-like giant cells. On ultrastructural examination, rich intermediate filaments, and well-developed Golgi apparati and rough endoplasmic reticulum, were seen. Immunophenotypically, OHK lacked T and B cell-associated antigens, and had CD10, CD30, CD33 and CD138 antigens. Although OHK cells did not express immunoglobulin (Ig) protein, Southern blot analysis demonstrated clonal rearrangements of Ig heavy and light chain genes. These observations suggest that OHK cells are derived from preterminally differentiated B cells, and that they have features of PEL. Kaposi's sarcoma-associated herpesvirus and Epstein-Barr virus were not detected. OHK displayed hyperploid karyotypes with multiple structural abnormalities, and produced some cytokines such as macrophage-colony-stimulating factor (M-CSF), granulocyte-CSF, interleukin 6 and transforming growth factor beta 1. In particular, vascular endothelial growth factor (VEGF), whose stimulation of vascular permeability is thought to be critical to the pathogenesis of PEL, was also produced in large quantities. These results indicate that OHK may be a useful tool for the investigation of PEL.


METALIC reveals interorganelle lipid flux in live cells by enzymatic mass tagging.
The distinct activities of organelles depend on the proper function of their membranes. Coordinated membrane biogenesis of different organelles necessitates lipid transport from their site of synthesis to their destination. Several factors have been proposed to participate in lipid distribution, but despite its basic importance, in vivo evidence linking the absence of putative transport pathways to specific transport defects remains scarce. A reason for this scarcity is the near absence of in vivo lipid trafficking assays. Here we introduce a versatile method named METALIC (Mass tagging-Enabled TrAcking of Lipids In Cells) to track interorganelle lipid flux inside cells. In this strategy, two enzymes, one directed to a 'donor' and the other to an 'acceptor' organelle, add two distinct mass tags to lipids. Mass-spectrometry-based detection of lipids bearing the two mass tags is then used to quantify exchange between the two organelles. By applying this approach, we show that the ERMES and Vps13-Mcp1 complexes have transport activity in vivo, and unravel their relative contributions to endoplasmic reticulum-mitochondria lipid exchange.


SMN loss dysregulates microtubule-associated proteins in spinal muscular atrophy model.
Spinal muscular atrophy (SMA) is a rare neurodegenerative disease caused by the absence of survival motor neuron (SMN) protein. SMN loss results in impairments of the cytoskeleton, including microtubules and regulatory proteins. However, the contribution of microtubule-associated proteins (MAPs) to microtubule dysregulations in SMA is not fully understood. In this study, we investigated neuronal MAPs responsible for the microtubule stability and growth, including MAP1A, MAP2, MAP6, MAP7, EB1, and EB3 using an in vitro model of SMA. Decreased MAP2 and EB3 levels were found in SMN-deficient motor neuron-like cells, and EB3 protein level was also relevant to MAP1B. SMN loss leads to an increase in EB3 comet numbers at proximal neurites, indicating increased microtubule growth. Our findings suggest that SMN deficiency simultaneously causes dysregulations of several MAPs, contributing to the perturbations of microtubule dynamics in SMA.


Spatial redistribution and enantiomeric signatures of hexachlorocyclohexanes in Chinese forest soils: Implications to environmental behavior and influencing factors.
Hexachlorocyclohexanes (HCHs) are a group of highly persistent pesticides. The concentrations of HCHs and the enantiomeric fractions of α-HCH in the O- and A-horizons from 30 mountains across China were analyzed in this study. The concentrations of total HCHs ranged from 0.061 to 46.9 ng/g (mean 2.12 ng/g) and 0.046 to 16.1 ng/g (mean 0.792 ng/g) in the O- and A-horizons, respectively. The HCH residues were mainly derived from the historical applications of technical HCH and lindane. Higher concentrations of HCHs were typically found in northern China, and no significant correlations were found between historical technical HCH usage and HCH isomer concentrations in either the O- or A-horizons (p > 0.05). Conversely, the concentrations of HCH isomers were significantly correlated with the environmental parameters (temperature and precipitation), thus indicating a typical secondary distribution pattern. Some HCH isomers tended to be transported northward under the long-term effect of monsoon. Chiral α-HCH was non-racemic in soils and showed preferential degradation of (-) α-HCH in both the O- and A-horizons. The transformation from γ-HCH to α-HCH might alter the enantiomeric signatures of α-HCH in soils. Moreover, the deviation from racemic of α-HCH was positively correlated with the C/N ratio in the A-horizon (p < 0.01), thus suggesting that the C/N ratio could alter the microbial activity and significantly affect the enantioselective degradation extent of α-HCH in soils.


What causes the aphid 28S rRNA to lack the hidden break?
In order to determine why the aphid 28S rRNA lacks the hidden break otherwise found in insects, the structure of the region of the aphid ribosomal DNA (rDNA) corresponding to the gap region, which in other insect rDNA transcripts is excised posttranscriptionally, was studied. Sequence comparison suggested that, in contradistinction to what is found in rDNA transcripts of other insects, a stem-loop structure formed in this region of the aphid rDNA transcript is not AU-rich. Nor did the loop of the aphid molecule contain the UAAU tract that can be a signal for the introduction of the hidden break, suggesting that in this particular region the aphid 28S rRNA resembles 28S rRNAs of deuterostomes, which do not contain the hidden break.


Inhibition of antibody production by 2-chloroadenosine.
The ability of 2-chloroadenosine (2Cl Ado) to modulate lymphocyte function was examined in culture and in vivo. Mitogenic stimulation of B cell DNA synthesis was antagonized by 2Cl Ado while adenosine produced both stimulations and inhibitions. In culture, 2Cl Ado was found to suppress antibody production to sheep erythrocytes (SRBC) regardless of whether the nucleoside was added at the initiation of culture or 48 hours after sensitization. Inhibiting adenosine deaminase (ADA) did not affect the response to 2Cl Ado, and 1-homocysteine thiolactone was found to potentiate the inhibition suggesting formation of S-adenosylhomocysteine. Similar responses were found with adenosine provided ADA was inhibited. When 2Cl Ado was administered to mice 3-4 days after SRBC, a concentration-dependent decrease in antibody producing cells was observed. These data suggest that nucleosides can inhibit antibody production by inhibiting transmethylation reactions. 2Cl Ado appears to be an effective immunosuppressant without concomitant cytotoxicity both in culture and in vivo.


Marching band model for simulating a single muscle fiber action potential.
We describe a mathematical model to calculate a single muscle fiber action potential (AP). Based on a marching band pattern, it is an enhancement to our previously described "modified line source" model. Calculations were performed using an Excel spread sheet. AP was simulated for a 200 mm long muscle fiber with 60 µm diameter, propagation velocity of 4 m/s, and end-plate located at the center. Several different electrode locations were used to calculate the AP. The AP amplitude was highest at the end-plate where the waveform was biphasic with initial negativity. When the electrode was moved towards the tendon, the amplitude decreased for the first 1.5 mm. The AP was triphasic and its waveform was relatively constant at electrode positions beyond 1.5 mm from the end-plate. It matched the calculations using the modified line source model. When the electrode was near the tendon, the AP amplitude decreased asymmetrically and waveform became biphasic resembling a positive sharp wave. The model is conceptually and computationally simple. It simulated the expected AP shape at different electrode positions along the muscle fiber. The waveforms are similar to those obtained from mathematically complex volume conductor models. The revised model can be useful for teaching and future simulation studies.


A prospective study of the active management of labor in women of high parity.
High parity has been suggested as contra-indication for the use of oxytocin stimulation in labor. The aim of our study was to prospectively evaluate a protocol of oxytocin administration in 130 consecutive low-risk patients having their sixth or subsequent delivery. Induction of labor failed only in 5 cases. No adverse effect on maternal and perinatal outcome was found. We conclude that with the introduction of electronic fetal monitoring and direct recording of uterine activity, oxytocin can be safely used for low-risk grand multiparae.


How old is too old for in vitro maturation (IVM) treatment?
Fertility declines with age. A study of the outcomes of in vitro maturation (IVM) in women of different ages has not been reported to date. The aim of our study was to evaluate the impact of age on treatment response and on pregnancy rates after IVM treatment. We reviewed the data of all IVM cycles and recorded the total number of oocytes, total metaphase II (MII) oocytes, the number and quality of embryos as well as pregnancy rates. The main outcome measures were number and maturity of retrieved oocytes and pregnancy rates. Compared to cycles in women ≤25 years, the number of oocytes and total MII oocytes were significantly lower in women over 40 years. The number of good quality embryos in women ≤25 years (3.6±1.7) was higher than in women aged 40 years (0.8±1.2, P<0.0001). The ongoing pregnancy rates in women aged 20-25 years were 36.8%, 26-35 years were 30.0% and in those 36-39 years were 31.9%. No clinical pregnancy was observed in women over the age of 40. Women over 40 years are poor candidates for IVM treatment.


Phylogenetic affinity of a wide, vacuolate, nitrate-accumulating Beggiatoa sp. from Monterey Canyon, California, with Thioploca spp.
Environmentally dominant members of the genus Beggiatoa and Thioploca spp. are united by unique morphological and physiological adaptations (S. C. McHatton, J. P. Barry, H. W. Jannasch, and D. C. Nelson, Appl. Environ. Microbiol. 62:954-958, 1996). These adaptations include the presence of very wide filaments (width, 12 to 160 microm), the presence of a central vacuole comprising roughly 80% of the cellular biovolume, and the capacity to internally concentrate nitrate at levels ranging from 150 to 500 mM. Until recently, the genera Beggiatoa and Thioploca were recognized and differentiated on the basis of morphology alone; they were distinguished by the fact that numerous Thioploca filaments are contained within a common polysaccharide sheath, while Beggiatoa filaments occur singly. Vacuolate Beggiatoa or Thioploca spp. can dominate a variety of marine sediments, seeps, and vents, and it has been proposed (H. Fossing, V. A. Gallardo, B. B. Jorgensen, M. Huttel, L. P. Nielsen, H. Schulz, D. E. Canfield, S. Forster, R. N. Glud, J. K. Gundersen, J. Kuver, N. B. Ramsing, A. Teske, B. Thamdrup, and O. Ulloa, Nature [London] 374:713-715, 1995) that members of the genus Thioploca are responsible for a significant portion of total marine denitrification. In order to investigate the phylogeny of an environmentally dominant Beggiatoa sp., we analyzed complete 16S rRNA gene sequence data obtained from a natural population found in Monterey Canyon cold seeps. Restriction fragment length polymorphism analysis of a clone library revealed a dominant clone, which gave rise to a putative Monterey Beggiatoa 16S rRNA sequence. Fluorescent in situ hybridization with a sequence-specific probe confirmed that this sequence originated from wide Beggiatoa filaments (width, 65 to 85 microm). A phylogenetic tree based on evolutionary distances indicated that the Monterey Beggiatoa sp. falls in the gamma subdivision of the class Proteobacteria and is most closely related to the genus Thioploca. This vacuolate Beggiatoa-Thioploca cluster and a more distantly related freshwater Beggiatoa species cluster form a distinct phylogenetic group.


[Sources used to obtain information on COVID-19 and its impact on mental health.]
With the rise of COVID-19, the society has had the need to search for information about the pandemic and the sources used to obtain information have been very diverse, with a greater predominance of social media, traditional media and consultation with loved ones. In addition, an excess of information has been observed in the media that made access and understanding difficult, as well as a constant concern and anxiety about health that caused a need to search excessively or repeatedly for information on health and disease. This information was not always endorsed by the scientific community and during the pandemic there has been the spread of misinformation, fake news and conspiracy theories about COVID-19 disseminated, mainly through social media. In this sense, both the knowledge and the beliefs apprehended have been able to impact the mental health of the population.


Use of professional practice guidance resources in pharmacy: a cross-sectional nationwide survey of pharmacists, intern pharmacists, and pharmacy students.
Variations in practice are commonplace in healthcare where health professionals, such as pharmacists act as autonomous practitioners. This is evident in simulated patient studies, where pharmacists practice does not meet widely accepted standards for medicines supply or treatment of an ailment. To promote best pharmacy practice a myriad of guidance resources including practice guidelines, codes and standards are produced by professional organisations. These resources provide a framework for pharmacy practice and endeavour to facilitate consistency in provision of pharmacy-based services to consumers. Despite their role in specifying essential pharmacist behaviours, there is limited research exploring if and how these resources are used in practice. To characterise Australian pharmacists' use of the Pharmaceutical Society of Australia's Code of Ethics, Professional Practice Guidelines and Professional Practice Standards. A cross-sectional, self-administered, electronic survey of registered pharmacists, intern pharmacists and pharmacy students living in Australia was conducted in July 2020. Questions considered use of professional practice resources (by resource group) in the preceding 12 months. Data were analysed descriptively. Of 601 responses included in the analysis 462 (76.9%) of respondents were registered pharmacists, 88 (14.6%) pharmacy students and 51 (8.5%) intern pharmacists. Interns and students accessed overarching practice resources, such as the Professional Practice Standards, Code of Ethics and Dispensing Practice Guidelines more frequently than practising pharmacists. Pharmacists accessed professional practice guidelines, such as Practice Guidelines for the Provision of Immunisation Services Within Pharmacy, more often than students. More pharmacists than interns and students indicated that they would access guidelines to resolve practice and patient care issues. All resources except the Professional Practice Standards for Pharmacists (67.4%) were accessed by less than 50% of respondents in the preceding 12-month period. Reasons for not accessing resources varied between participant and resource groups, and generally were due to a lack of awareness of the resource or not considering them necessary for the individual's practice. Access and use patterns for professional practice guidance resources change with experience. Professional organisations responsible for developing resources should consider these patterns when designing and reviewing resources and related policies. To ensure resources are meeting the needs of the profession, students, interns, and pharmacists should be involved in the review of and design of further resources.


Discordance in 21-gene recurrence scores between paired breast cancer samples is inversely associated with patient age.
The Oncotype DX 21-gene Recurrence Score is a genomic-based algorithm that guides adjuvant chemotherapy treatment decisions for women with early-stage, oestrogen receptor (ER)-positive breast cancer. However, there are age-related differences in chemotherapy benefit for women with intermediate Oncotype DX Recurrence Scores that are not well understood. Menstrual cycling in younger women is associated with hormonal fluctuations that might affect the expression of genomic predictive biomarkers and alter Recurrence Scores. Here, we use paired human breast cancer samples to demonstrate that the clinically employed Oncotype DX algorithm is critically affected by patient age. RNA was extracted from 25 pairs of formalin-fixed paraffin-embedded, invasive ER-positive breast cancer samples that had been collected approximately 2 weeks apart. A 21-gene signature analogous to the Oncotype DX platform was assessed through quantitative real-time PCR, and experimental recurrence scores were calculated using the Oncotype DX algorithm. There was a significant inverse association between patient age and discordance in the recurrence score. For every 1-year decrease in age, discordance in recurrence scores between paired samples increased by 0.08 units (95% CI - 0.14, - 0.01; p = 0.017). Discordance in recurrence scores for women under the age of 50 was driven primarily by proliferation- and HER2-associated genes. The Oncotype DX 21-gene Recurrence Score algorithm is critically affected by patient age. These findings emphasise the need for the consideration of patient age, particularly for women younger than 50, in the development and application of genomic-based algorithms for breast cancer care.


Photopatch testing in a tropical country, Thailand: 20 years' experience.
Photoallergic contact dermatitis is one of the important parts of photodermatoses. The investigation of choice is photopatch testing. However, reports with photopatch test results from Asian countries are scarce. The objective of this study was to determine the prevalence of positive photopatch test reactions and to ascertain the common photoallergens among Thai patients during 1998-2018. We retrospectively reviewed the records of 339 patients who were clinically suspected of having photoallergic contact dermatitis and had undergone photopatch testing. A total of 44 photoallergic contact reactions in 38 patients (11.2%) were found. The positive photoallergic reactions were mainly found with organic ultraviolet filters and fragrances. Organic ultraviolet filter chemicals especially benzophenone-3 and fragrances were found to have a high prevalence of photoallergic contact reactions. Monitoring of the photoallergens employed in photopatch tests should be conducted periodically to provide the best patient care.


Baseline cognitive function predicts full remission of suicidal symptoms among patients with treatment-resistant depression and strong suicidal ideation after low-dose ketamine infusion.
Whether pretreatment working memory and response inhibition function are associated with the rapid and sustained antisuicidal effect of low-dose ketamine among patients with treatment-resistant depression (TRD) and strong suicidal ideation is unclear. We enrolled 65 patients with TRD, comprising 33 who received a single infusion of 0.5 mg/kg ketamine and 32 who received a placebo infusion. The participants performed working memory and go/no-go tasks prior to infusion. We assessed suicidal symptoms at baseline and on postinfusion Days 2, 3, 5, and 7. The full remission of suicidal symptoms persisted for 3 days after a single ketamine infusion and the ketamine-related antisuicidal effect persisted for 1 week. Lower cognitive impairment at baseline (indicated by a higher rate of correct responses on a working memory task) was associated with the rapid and sustained antisuicidal effect of low-dose ketamine in patients with TRD and strong suicidal ideation. Patients with TRD and strong suicidal ideation but low cognitive impairment may benefit the most from the antisuicidal effect of low-dose ketamine.


Anti-Ia reactivity in sera from subjects with Entamoeba histolytica infection.
Sera from 15 patients with Entamoeba histolytica infection were tested for anti T-cell antibodies by assessing cross-reacting specificities with the antigens defined by an anti-Ia hybridoma antibody. T cells prepared by sheep erythrocyte rosetting were preincubated with the test sera and then with the anti-Ia antibody. Binding of the specific monoclonal antibody was assessed by rosetting with ox erythrocytes conjugated with goat anti-mouse IgG. Eight sera from amoebic patients were found to block the binding of monoclonal mouse hybridoma anti Ia-antibody to T cells. Blocking of anti-Ia binding was not due to Fc IgG receptor binding by immune complexes nor was it HLA-DR restricted. T cells pre-treatment with the amoebic sera positive for anti-Ia activity showed reduced activity when tested in the autologous mixed lymphocyte reaction (AMLR). The results of our study seem to suggest the existence of specific anomalies of immunoregulation during E. histolytica infection which may play a role in inducing immune disregulation in vivo.


Pediatric upper airway obstruction due to ectopic thyroid: classification and case reports.
Few clinical situations can be as frightening, challenging, and as rewarding as stabilizing the airway of a child. Most causes of pediatric upper airway obstruction are well recognized, often discussed in the literature, and commonly encountered in practice. However, ectopic thyroid (i.e., thyroid tissue found in places other than its normal location) may be an unusual cause of pediatric upper airway obstruction with which the clinician may not be familiar. The resulting airway obstruction may be slow or rapid in onset, total or partial, and the relationship of the thyroid to the airway may be clear or obscure. Two cases of obstructing ectopic thyroid are presented which demonstrate the spectrum within which this form of airway obstruction may occur. One case is the first reported example in the English literature of pediatric intratracheal thyroid. A review of the literature is also presented. Four types of ectopic thyroid (lingual, sublingual, thyroglossal, and intralaryngotracheal) are illustrated and discussed in relation to their effect upon the pediatric upper airway. The authors also review the developmental anatomy of the thyroid and present two major theories regarding the development of intralaryngotracheal thyroid. The possible etiologies of the other ectopic forms are also discussed.


IL-2 and GM-CSF are regulated by DNA demethylation during activation of T cells, B cells and macrophages.
DNA demethylation has been found to occur at the promoters of a number of actively expressed cytokines and is believed to play a critical role in transcriptional regulation. While many DNA demethylation studies have focused on T cell activation, proliferation and differentiation, changes in DNA methylation in other types of immune cells are less well studied. We found that the expression of two cytokines (IL-2 and GM-CSF) responded differently to activation in three types of immune cells: EL4, A20 and RAW264.7 cells. Using the McrBC and MeDIP approaches, we observed decreases in DNA methylation at a genome-wide level and at the promoters of the genes of these cytokines. The expression of several potential enzymes/co-enzymes involved in the DNA demethylation pathways seemed to be associated with immune cell activation.


Martin's Map: a conceptual framework for teaching and learning the medical interview using a patient-centred approach.
At the end of training, students seem to lack a basic understanding of how to take an organised, relevant medical and social history using a patient-centred approach. The aim of developing the map described in this paper was to provide a framework for such an approach. Action research was used to continuously modify and refine an interview map that was used by medical clerks, family medicine residents, international medical graduates and practising doctors for teaching and learning purposes over a 10-year period. 'Martin's Map' provides a realistic framework for flexibly organising and integrating medical content with process that did not previously exist. The map provides medical educators with a standardised framework for talking about the medical interview, which helps learners understand how to use their medical knowledge with a patient-centred approach. Learners are able to visually see how they can take a focused medical and social history using a patient-centred approach, which subsequently seems to help them organise their thinking and approach during the medical encounter.


Propargyl 1,2-orthoesters for stereoselective synthesis of thioglycosides and 1-thiotrehaloses.
Various thiosaccharides and 1-thiotrehaloses were synthesized exploiting salient features of gold-catalyzed glycosidation repertoire using alkynyl 1,2-orthoesters as glycosyl donors. The reaction was found to be general, high yielding, diastereoselective, fast, mild and catalytic.


First description of Lachnoanaerobaculum orale as a possible cause of human bacteremia.
Lachnoanaerobaculum spp. is an obligate anaerobic, gram-positive, spore-forming, rod-shaped bacillus. Here, we report the first known case of bacteremia due to L. orale, which was detected in a patient with acute lymphoblastic leukemia. A 69-year-old man developed neutropenic fever with severe stomatitis during chemotherapy for leukemia. The bacteria strain isolated from blood culture was successfully identified as L. orale via matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS). Susceptibility testing revealed that the strains showed low minimum inhibitory concentrations (MICs) of beta-lactams, clindamycin, and metronidazole, but higher MICs of fluoroquinolones. The present case study indicates that Lachnoanaerobaculum can be a cause of human infection, including bloodstream infection.


In vitro effect of heather extracts on Trichostrongylus colubriformis eggs, larvae and adults.
This study was carried out to evaluate the in vitro effects of different heather species on Trichostrongylus colubriformis eggs, larvae and adult worms, and obtain scientific evidence to attribute these effects to the action of their phenolic compounds and/or tannins. Total phenolic extracts of three heather species (Calluna vulgaris, Erica cinerea, and Erica umbellata) and an equal mixture of these three extracts were tested in vitro in the three development stages of T. colubriformis using an egg hatching assay (EHA), larval exsheathment inhibition assay (LEIA), and adult motility inhibition assay (AMIA). The egg hatching rate was measured after incubation with heather extracts for 48 h at 25°C. Infective third-stage larvae (L3) were incubated for 3h at 25°C with heather extracts. The evolution of artificial exsheathment over time was measured with repeated observations at 20-min intervals for 60 min. Adult worms were obtained from one donor goat and incubated with the extracts at 37°C for 5 days in 48-multiwell plates. Worm motility was measured at 0, 19, 24, 43, 48, 67, 72, 96 and 115 h after the beginning of the experiment. The extracts were tested at concentrations of 75, 150, 300, 600 and 1,200 μg/ml. All extracts significantly (P<0.001) inhibited egg hatching and the effect was dose dependent. All extracts inhibited or delayed the exsheathment of T. colubriformis L3, and the effect was dose dependent for C. vulgaris. Incubation with heather extracts induced a reduction in adult worm motility compared to control, although significant (P<0.05) differences were only found at the highest concentrations. Additional studies showed that purified tannins of the same heather species disturbed T. colubriformis larval exsheathment. All these results confirm the anthelmintic properties of heather against T. colubriformis, and suggest that not only tannins but also some other phenolic compounds might be involved.


Four-year outcomes from the Early Re-Intervention (ERI) experiment using Recovery Management Checkups (RMCs).
While drug abuse is the 10th leading cause of mortality in the US, the public health care system has been slow to adopt a chronic disease approach with aggressively timed monitoring and interventions. Drug abuse remains isolated from adoption into the "chronic condition" model of care. This paper evaluates the efficacy of quarterly Recovery Management Checkups (RMCs) on treatment reentry and long-term substance use in the context of chronic substance use disorders. 446 adult substance users were randomly assigned to RMC or a control group and assessed quarterly for 4 years (94% completion). The main outcome measures were: time from need of treatment to treatment reentry, frequency of treatment reentry, days of treatment, number of substance use related problems per month, and total days abstinent. Participants in the RMC condition were significantly more likely than participants in the control group to return to treatment sooner, to return at all, to return more times, and to receive more total days of treatment. They subsequently had significantly fewer quarters in need of treatment, fewer substance related problems per month, and more total days of abstinence. Effects were larger for those with earlier onset and higher crime/violence scores. RMC is an effective method of monitoring and re-intervening with chronic substance users and is associated with improved long-term outcomes. A subgroup of people for whom RMC did not appear to be "enough," signals a need to explore more intensive models to address chronicity.


WITHDRAWN:Development of Dot Enzyme Linked Immuno Sorbent Assay Using Recombinant Hexon Protein for Detecting Antibodies to Hydropericardium Syndrome Disease Virus.
Ahead of Print article withdrawn by publisher.


cAMP-dependent protein kinase and lipolysis in rat adipocytes. II. Definition of steady-state relationship with lipolytic and antilipolytic modulators.
The steady-state relationship between the activation state of cAMP-dependent protein kinase (A-kinase) and lipolysis has been defined quantitatively. A-kinase activation was assessed by measuring the ( +/- cAMP) activity ratio in adipocyte extracts, and lipolysis was determined by measuring glycerol release from cells. Both processes were stimulated either by incubating cells in a ligand-free environment achieved with adenosine deaminase or by addition of lipolytic hormones. A response spectrum was obtained with a variety of adenylate cyclase stimulators and inhibitors, both receptor- and nonreceptor-mediated. Regardless of the ligands used to manipulate adipocyte activity, lipolysis varied from nil to maximal as the A-kinase activity ratio varied from approximately 0.05 to 0.3-0.35. These data provide a quantitative description of the steady-state relationship between A-kinase activity and lipolysis and indicate that the various lipolytic and antilipolytic agents tested act on the lipolytic process exclusively by altering adenylate cyclase activity and, thus, cellular cAMP concentrations. The data reveal also that transient "peaking" of cAMP, as measured by A-kinase activity ratios, is not an inherent feature of adipocyte metabolism. Moreover, the concentration requirements for lipolytic hormone action are critically dependent on the ambient concentration of antilipolytic agents, and t concentration requirements for antilipolytic agents are dependent on the extent to which cells are stimulated. The data in this paper provide the basis for assessing the relationship between A-kinase activity ratio and lipolysis in the presence of insulin (Londos, C., Honnor, R. C., and Dhillon, G. S. (1985) J. Biol. Chem. 260, 15139-15145).


Serum soluble urokinase plasminogen activator receptor as a potential biomarker of renal impairment severity in diabetic nephropathy.
To investigate serum soluble form of urokinase-type plasminogen activator receptor (suPAR) in patients with diabetic kidney disease (DKD) and biopsy-proven diabetic nephropathy (DN), its correlation with histological parameters and its capacity as a biomarker for renal impairment severity. We conducted a cross-sectional study on 75 patients with diabetes mellitus (DM) and DKD, among whom 28 had biopsy-proven DN. Among the 75 patients, 9 (12%) had type 1 and 66 (88%) type 2 DM. The median value of the serum suPAR level was 2857.2 pg/mL (1916.4-3700) in the entire cohort and 2472.1 pg/mL (1782.6-3745.8) in the biopsy-proven DN subgroup, respectively. suPAR was significantly correlated with diabetes duration, diabetic retinopathy, anti-proteinuric treatment, albuminuria, kidney function, DN class, interstitial fibrosis and tubular atrophy (IFTA) score and with interstitial inflammation score. suPAR had a good accuracy for the association with chronic kidney disease (CKD) stages G3b-5, macroalbuminuria, DN class IV, IFTA score 3 and interstitial inflammation score 2. Serum suPAR was increased in DN patients and was associated with DM duration, diabetic retinopathy, renoprotective treatment, kidney function, proteinuria, DN class, IFTA and interstitial inflammation scores. Also, suPAR had a good capacity as a biomarker for advanced renal impairment and severe histological lesions of DN.


Adaptive changes results in activation of alternate signaling pathways and resistance to aromatase inhibitor resistance.
Hormone therapy is an effective approach for the treatment of breast cancer. The antiestrogen tamoxifen has had a major impact on the disease. Recently, aromatase inhibitors which reduce estrogen synthesis have proved to be more effective and these agents are now used as first line therapy for postmenopausal breast cancer. Nevertheless, resistance to treatment eventually may occur. We have investigated mechanisms involved in resistance to AIs and devised strategies to overcome the resistance. Using a xenograft model, we have identified adaptive changes that results in activation of alternate signaling pathways in tumors resistant to aromatase inhibitors. Expression of ERα and aromatase was decreased in the tumors after long term treatment with AIs. In contrast increased expression was observed of tyrosine kinase receptors such as HER-2 and IGFR as well as of downstream signaling proteins, including MAPK. We have demonstrated functional activation of the MAPKinase pathway and shown dependency on growth factor receptor signaling in letrozole resistant cells. Furthermore, our studies indicate that HER-2 is a negative regulator of ER. Thus, when HER-2 was blocked with antibody (herceptin, trastuzumab) ER expression was increased rendering the cells and tumors responsive to aromatase inhibitors and resulting in tumor regression.


Early developmental outcome following surgery for oesophageal atresia.
To compare the developmental outcome of infants with oesophageal atresia with or without trachea-oesophageal fistula (OA/TOF) who underwent surgery in early infancy with healthy control infants in New South Wales, Australia. Infants diagnosed with OA/TOF requiring surgical intervention were enrolled prospectively between 1 August 2006 and the 31 December 2008. Healthy control infants were enrolled in the same time period. The children underwent a developmental assessment at 1 year of age (corrected) using the Bayley Scales of Infant and Toddler Development (Version III). Of 34 infants with OA/TOF that were enrolled, 31 had developmental assessments. The majority (75%) were term infants (≥37 weeks gestation) with a mean birth weight of 2717 g. Fourteen infants (44%) had an associated birth defect and one infant with multiple associated anomalies subsequently died. Developmental assessments were also performed on 62 control infants matched for gestational age. Infants with OA/TOF had a mean score significantly lower on the expressive language subscale (P < 0.05) compared with the control infants. This study found a lower than expected developmental score for infants following surgery for OA/TOF in the expressive language subscale compared with the healthy control infants. These findings support concerns over the potential impact of OA/TOF and its effects on development. Further studies, including continuing developmental review to determine whether these differences persist and their functional importance, should be performed.


Aging-related changes in cutaneous corticotropin-releasing hormone system reflect a defective neuroendocrine-stress response in aging.
Skin, being a mirror of the body, is a major target for aging research. Aging is a complex process that involves the decline of function or dysfunction of many systems. The corticotropin-releasing hormone (CRH) system is involved in skin inflammation. In addition, CRH has a suggested role in age-associated conditions and in animal aging models. However, a consistent logic interaction between the different CRH system components and the aging process has, to our knowledge, never been examined before. The expression of CRH, CRH-binding protein (CRHBP), CRH receptor 1 (CRHR1), and CRH receptor 2 (CRHR2) in healthy skin samples of 42 patients of different ages (18-92 years) was evaluated by immunohistochemistry, and the age-related changes were assessed. Compared with young skin, the aged skin displayed an upregulation of CRH in sebaceous glands and CRHR1 in hair follicles and the epidermis. Moreover, age-associated downregulation of CRHBP in the sebaceous and sweat glands was detected, whereas the CRHR2 showed no age-related changes. Our findings suggest that the age-associated changes in the expression of CRH system components reflect an exaggerated stress response reaction, putting the aged skin continuously in a stress-like situation.


Correction of the soft tissue pollybeak using triamcinolone injection.
To describe the technique for correction of the soft tissue pollybeak deformity using intralesional injection of triamcinolone acetonide. We discuss our philosophy, regimen, and technique for treatment of the soft tissue pollybeak using triamcinolone injection. We include results from a series of 173 patients who underwent rhinoplasty performed by one of us (N.J.P.). Triamcinolone was injected at 1 week after surgery in 127 patients (73%). A second injection was performed in 92 (72%) of the 127 patients at 4 weeks after surgery. One hundred eight (85%) of the 127 patients had an acceptable result, as judged by the surgeon, with good supratip definition. Nineteen (15%) of the 127 patients had a less than optimal result, with residual supratip fullness, as judged by the surgeon. There were no complications caused by triamcinolone injection. Because revision surgery is difficult and may be associated with complications, intralesional triamcinolone injection is the first-line treatment for the soft tissue pollybeak deformities caused by subdermal scarring. Should intralesional steroid injection fail to satisfactorily treat the deformity, revision rhinoplasty can subsequently be performed.


PEEP decreases atelectasis and extravascular lung water but not lung tissue volume in surfactant-washout lung injury.
To examine the effects of positive end-expiratory pressure (PEEP) on extravascular lung water (EVLW), lung tissue, and lung volume. Experimental animal study at a university research facility. Fifteen adult sheep. All animals were studied before and after saline washout-induced lung injury while ventilated with sequentially increasing PEEP (0, 7, 14, or 21 cmH(2)O). Lung volume was determined by computed tomography and EVLW by the thermal dye dilution technique. Saline washout significantly increased lung tissue volume (21+/-3 to 37+/-5 ml/kg) and EVLW (9+/-2 to 36+/-9 ml/kg). While increasing levels of PEEP reduced EVLW (30+/-7, 24+/-8, and 18+/-4 ml/kg), lung tissue volume remained constant. Total lung volume significantly increased (50+/-8 ml/kg at PEEP 0 to 77+/-12 ml/kg at PEEP 21). Nonaerated lung volume significantly decreased and was closely correlated with the changes in EVLW ( r=0.67). In addition, a highly significant correlation was found between PEEP-induced decrease in nonaerated lung volume and decrease in transpulmonary shunt ( r=0.83). The main findings are as follows: (a) PEEP effectively decreases EVLW. (b) The decrease in EVLW is closely correlated with the PEEP-induced decrease in nonaerated lung volume, making EVLW a valuable bedside parameter indicating alveolar recruitment, similar to measurements of transpulmonary shunt. (c) As excess tissue volume remained constant, however, EVLW may not be suitable to reflect overall severity of lung disease


Predicting and comparing three corrective techniques for sagittal craniosynostosis.
Sagittal synostosis is the most occurring form of craniosynostosis, resulting in calvarial deformation and possible long-term neurocognitive deficits. Several surgical techniques have been developed to correct these issues. Debates as to the most optimal approach are still ongoing. Finite element method is a computational tool that's shown to assist with the management of craniosynostosis. The aim of this study was to compare and predict the outcomes of three reconstruction methods for sagittal craniosynostosis. Here, a generic finite element model was developed based on a patient at 4 months of age and was virtually reconstructed under all three different techniques. Calvarial growth was simulated to predict the skull morphology and the impact of different reconstruction techniques on the brain growth up to 60 months of age. Predicted morphology was then compared with in vivo and literature data. Our results show a promising resemblance to morphological outcomes at follow up. Morphological characteristics between considered techniques were also captured in our predictions. Pressure outcomes across the brain highlight the potential impact that different techniques have on growth. This study lays the foundation for further investigation into additional reconstructive techniques for sagittal synostosis with the long-term vision of optimizing the management of craniosynostosis.


Auditory novelty processing is enhanced in obsessive-compulsive disorder.
Cognitive models propose that anxiety disorders are associated with an attentional bias toward potentially threatening stimuli. In this study, it was analyzed whether patients with obsessive-compulsive disorder (OCD) show enhanced responses of their event-related brain potentials to novel stimuli, either in a context of potential threat or in a neutral context. In this study, 20 OCD patients and 20 matched healthy control subjects performed a visual recognition task during which irrelevant repeated standard sounds and unitary novel sounds were interspersed. As expected, OCD patients showed an increase in the novelty-P3 amplitude elicited by unitary novel sounds. However, no effect of emotional context conditions was observed. It is suggested that the novelty P3 amplitude increase in OCD patients represents a physiological indicator of an enhanced cortical orienting response implicating stronger involuntary shifts of attention. This characteristic is driven by novelty per se and not moderated by potential threat of upcoming events.


Post-streptococcal scleredema an unusual rare mimicker of scleroderma: a case report.
cleredema of Buschke is a rare pathological disorder of connective tissue, which is characterized by a woody, diffuse induration of the skin, most often in the upper extremities. We report an extremely rare complication of post-streptococcal infection in a six-year-old male complaining of gradually progressing, painless skin thickening and tightness which was preceded by a one-month history of fever, cough, and tonsillitis. By reporting this case, we hope to contribute to the creation of a database for future research aimed at better understanding the incidence, pathophysiology, and management of this extremely rare complication.


Shifting eating to the circadian rest phase misaligns the peripheral clocks with the master SCN clock and leads to a metabolic syndrome.
The light-entrained master central circadian clock (CC) located in the suprachiasmatic nucleus (SCN) not only controls the diurnal alternance of the active phase (the light period of the human light-dark cycle, but the mouse dark period) and the rest phase (the human dark period, but the mouse light period), but also synchronizes the ubiquitous peripheral CCs (PCCs) with these phases to maintain homeostasis. We recently elucidated in mice the molecular signals through which metabolic alterations induced on an unusual feeding schedule, taking place during the rest phase [i.e., restricted feeding (RF)], creates a 12-h PCC shift. Importantly, a previous study showed that the SCN CC is unaltered during RF, which creates a misalignment between the RF-shifted PCCs and the SCN CC-controlled phases of activity and rest. However, the molecular basis of SCN CC insensitivity to RF and its possible pathological consequences are mostly unknown. Here we deciphered, at the molecular level, how RF creates this misalignment. We demonstrate that the PPARα and glucagon receptors, the two instrumental transducers in the RF-induced shift of PCCs, are not expressed in the SCN, thereby preventing on RF a shift of the master SCN CC and creating the misalignment. Most importantly, this RF-induced misalignment leads to a misexpression (with respect to their normal physiological phase of expression) of numerous CC-controlled homeostatic genes, which in the long term generates in RF mice a number of metabolic pathologies including diabetes, obesity, and metabolic syndrome, which have been reported in humans engaged in shift work schedules.


Recent Advances on Genetic and Physiological Bases of In Vitro Somatic Embryo Formation.
Somatic embryogenesis involves a broad repertoire of genes, and complex expression patterns controlled by a concerted gene regulatory network. The present work describes this regulatory network focusing on the main aspects involved, with the aim of providing a deeper insight into understanding the total reprogramming of cells into a new organism through a somatic way. To the aim, the chromatin remodeling necessary to totipotent stem cell establishment is described, as the activity of numerous transcription factors necessary to cellular totipotency reprogramming. The eliciting effects of various plant growth regulators on the induction of somatic embryogenesis is also described and put in relation with the activity of specific transcription factors. The role of programmed cell death in the process, and the related function of specific hemoglobins as anti-stress and anti-death compounds is also described. The tools for biotechnology coming from this information is highlighted in the concluding remarks.