Measurement Error-Corrected Estimation of Clinically Significant Change Trajectories for Interventions Targeting Comorbid PTSD and Substance Use Disorders in OEF/OIF Veterans.
In randomized control trials (RCTs), a focus on average differences between treatment arms often limits our understanding of whether individuals show clinically significant improvement or deterioration. The present study examined differences in individual-level clinical significance trajectories between Concurrent Treatment of PTSD and Substance Use Disorders Using Prolonged Exposure (COPE) and Relapse Prevention (RP). Eighty-one treatment-seeking veterans with a comorbid PTSD/SUD diagnosis were randomized to COPE or RP; data from an additional n = 48 patients who did not meet criteria for both disorders was used to establish a normative threshold. A newly developed, modernized approach to the Jacobson and Truax (1991) clinically significant change framework, using (a) moderated nonlinear factor analysis (MNLFA) scale scoring and (b) measurement error-corrected multilevel modeling (MEC-MLM) was used; this approach was compared to other approaches using conventional total scores and/or assuming no measurement error. Using a conventional approach to estimating the Reliable Change Index (RCI) yielded no differences between COPE and RP in the percentage of patients achieving statistically significant improvement (SSI; 88.9% for both groups). However, under MNLFA/MEC-MLM, higher percentages of patients receiving COPE (75.0%) achieved SSI compared to RP (40.7%). Findings suggest that, even though COPE and RP appear to reduce the same number of PTSD symptoms, MNLFA scoring of outcome measures gives greater weight to interventions that target and reduce "hallmark" PTSD symptoms.


The pattern of recurrence of adenocarcinoma of the oesophago-gastric junction.
Knowledge of the pattern of recurrence of surgically treated cases of adenocarcinoma of the oesophago-gastric junction is important both for better understanding of their biological nature and for future strategic planning of therapy. The aim of this study is to demonstrate and compare the pattern of dissemination and recurrence in patients with Type I and Type II adenocarcinoma of oesophago-gastric junction. A prospective audit of the clinico-pathological features of patients who had undergone surgery with curative intent for adenocarcinoma of oesophago-gastric junction between 1991 and 1996 was undertaken. Patients were followed up by regular clinical examination. Clinical evaluation was supported by ultrasound, computerised tomography, radio-isotope bone scan, endoscopy and laparotomy each with biopsy and histology where appropriate. One hundred and sixty-nine patients with oesophago-gastric junction tumours (94 Type I and 75 Type II) have been followed up for a median of 75.3 (57-133) months. One hundred and three patients developed proven recurrent disease. The median time to recurrence was 23.3 (14.2-32.4) months for Type I and 20.5 (11.6-29.4) for Type II cancers. The most frequent type of recurrence was haematogenous (56% of Type I recurrences and 54% of Type II) of which 56% were detected within 1 year of surgery. The most frequent sites were to liver (27%), bone (18%) brain (11%) and lung (11%). Local recurrence occurred in 33% of Type I cancer and 29% of Type II recurrences. Nodal recurrence occurred in 18 and 25% of Type I and Type II cancer recurrences, most frequently to coeliac or porta hepatis nodes (64%). Only 7% of Type I and 15% of Type II cancer recurrences were by peritoneal dissemination. Type I and Type II adenocarcinoma of the oesophago-gastric junction have a predominantly early, haematogenous pattern of recurrence. There is a need to better identify the group of patients with small metastases at the time of diagnosis who are destined to develop recurrent disease in order that they may be spared surgery and those with micro metastases in order that they can be offered multi-modality therapy including early post operative or neo-adjuvant chemotherapy.


Photoaging and release profile of acrylonitrile butadiene styrene microplastics under simulated solar radiation in water.
Microplastics (MPs) pollution has become a major environmental problem and poses a risk to a variety of organisms. In this study, the photoaging behavior of acrylonitrile butadiene styrene microplastics (ABS-MP) in aqueous environment was investigated under simulated solar irradiation. Results showed that the long chains of ABS-MP broke under the light irradiation, and its thermal stability was reduced. ABS-MP was oxidized during photoaging and produced a large number of oxygen-containing functional groups. Structure destruction of ABS-MP decreased the formation of environmentally persistent free radicals (EPFRs) and further photoirradiation generated secondary EPFRs. Nuclear magnetic resonance (NMR) analysis of the aged leachates confirmed that ABS-MP was oxidized and some small molecular fragments were dropped during photoaging. Meanwhile, C-Br bond broke of additive tetrabromobisphenol A (TBBPA) resulting in more bromine released into water and Sb(III) of additive Sb2O3 was oxidized to Sb(V) during photoaging. These findings illustrate the necessity of considering the aging of MPs in natural environment, expand the understanding of the potential harm and fate of MPs in aqueous environment, which is important for the management of MPs.


Paternal postpartum depression's relationship to maternal pre and postpartum depression, and father-mother dyads marital satisfaction: A structural equation model analysis of a longitudinal study.
Fathers' depression is an understudied subject, and the increasing participation of fathers on the care of their children, this is an issue of great importance. This study aimed to determine the relationship of paternal postpartum depression with prenatal and postpartum depression of mothers and their marital satisfaction. This longitudinal study was conducted among 352 expecting couples in 28-40 weeks of pregnancy and 6-8 weeks after delivery from April to September 2019. Eligible participants were selected from primary health care centers in northern Iran using a two-stage sampling method. Socio-demographic information, Edinburgh Postpartum Depression Scale, and ENRICH Couple Scale were used for data collection. The primary basis of data analysis was cross-lagged structural equation modeling to explore the underlying mechanism for paternal postpartum depression. The results showed that a) maternal prenatal depression indirectly (βstand = 0.32, p = 0.004); b) maternal postpartum depression directly (βstand = 0.56, p <0.001); c) paternal prenatal depression indirectly (βstand = 0.11, p = 0.028) were associated with paternal postpartum depression. Also, marital satisfaction directly (βstand = -0.19, p = 0.002) and indirectly (βstand = -0.11, p = 0.007) had a relationship to paternal postpartum depression. Culturally-sensitive measures of marital satisfaction, especially in conservative context of developing countries, along with self-reported data of psychological problems may lead to under-reported findings. The major contribution of marital satisfaction and maternal depression during prenatal period on the paternal postpartum depression, emphasizes on the prenatal period as the ideal time for fathers' mental health improvement.


Improved Semiautomated 4D Flow MRI Analysis in the Aorta in Patients With Congenital Aortic Valve Anomalies Versus Tricuspid Aortic Valves.
The aim of this study was to systematically investigate a newly developed semiautomated workflow for the analysis of aortic 4-dimensional flow MRI and its ability to detect hemodynamic differences in patients with congenitally altered aortic valve (bicuspid or quadricuspid valves) compared with tricuspid aortic valves. Four-dimensional flow MRI data were acquired in 20 patients with aortic dilatation (9 tricuspid aortic valves, 11 congenitally altered aortic valves). A semiautomated workflow was evaluated regarding interobserver variability, accuracy of net flow, regurgitant fraction and peak systolic velocity, and the ability to detect differences between cohorts. Results were compared with manual segmentation of vessel contours. Despite the significantly reduced analysis time, a good interobserver agreement was found for net flow and peak systolic velocity, and a moderate agreement was found for regurgitation. Significant differences in peak velocities in the descending aorta (P = 0.014) could be detected. Four-dimensional flow MRI-based semiautomated analysis of aortic hemodynamics can be performed with good reproducibility and accuracy.


In silico characterization of atypical kinase PFD0975w from Plasmodium kinome: a suitable target for drug discovery.
RIO-2 kinase is known to regulate ribosome biogenesis and other cell cycle events. The 3D model of ATP bound and an unbound form of PFD0975w was generated using AfRIO-2 crystal structure 1TQI, 1ZAO as template employing Modeller9v7 program. Structural characterization identified N-terminal winged helix domain (1-84), C-terminal kinase domain (148-275), and presence of other critical residues known for ATP binding and kinase activity. Using Q-site and pocket finder, a number of well-defined substrate (peptide) binding regions were identified in the catalytic core of the protein. The peptide binding regions were further validated by molecular modeling a non-specific polyalanine peptide and a sequence-specific peptide2 into these sites to generate a stable PFD0975w/peptide complexes. Peptide fits well into identified pocket on PFD0975w and makes extensive interaction with the protein residues. These newly identified peptide binding sites potentially give opportunity to design a specific inhibitor against PFD0975w. There are subtle but significant differences between Plasmodium falciparum and human RIO-2 to exploit PFD0975w for drug development. In conclusion, our finding will let us to design effective chemotherapy against malaria parasite exploiting PFD0975w as a drug target.


Structural determinants of unexpected agonist activity in a retro-peptide analogue of the SDF-1alpha N-terminus.
We have synthesised two retro-peptide analogues of the stromal cell derived growth factor 1 (SDF-1alpha) segment known to be critical for CXCR4 receptor binding, corresponding to the sequences HSEFFRCPCRFFESH and HSEFFRGGGRFFESH. We have assayed the ability of these peptides to activate extracellular signal-regulated kinase 1/2 phosphorylation in cells over expressing the SDF-1alpha receptor, finding that the first variant was able to serve as an agonist of CXCR4, whereas the second one was inactive. Finally, by comparing representative solution structures of the two peptides, we have found that the biological response of HSEFFRCPCRFFESH may be ascribed to a beta-beta-type turn motif centred on Phe(4)-Phe(5).


Coarsening of antiferromagnetic domains in multilayers: the key role of magnetocrystalline anisotropy.
The domain structure of an antiferromagnetic superlattice is studied. Synchrotron Mössbauer and polarized neutron reflectometric maps show micrometer-size primary domain formation as the external field decreases from saturation to remanence. A secondary domain state consisting mainly of at least 1 order of magnitude larger domains is created when a small field along the layer magnetizations induces a bulk-spin-flop transition. The domain-size distribution is reproducibly dependent on the magnetic prehistory. The condition for domain coarsening is shown to be the equilibrium of the external field energy with the anisotropy energy.


Highly potent inhibitors of proprotein convertase furin as potential drugs for treatment of infectious diseases.
Optimization of our previously described peptidomimetic furin inhibitors was performed and yielded several analogs with a significantly improved activity. The most potent compounds containing an N-terminal 4- or 3-(guanidinomethyl)phenylacetyl residue inhibit furin with K(i) values of 16 and 8 pM, respectively. These analogs inhibit other proprotein convertases, such as PC1/3, PC4, PACE4, and PC5/6, with similar potency, whereas PC2, PC7, and trypsin-like serine proteases are poorly affected. Incubation of selected compounds with Madin-Darby canine kidney cells over a period of 96 h revealed that they exhibit great stability, making them suitable candidates for further studies in cell culture. Two of the most potent derivatives were used to inhibit the hemagglutinin cleavage and viral propagation of a highly pathogenic avian H7N1 influenza virus strain. The treatment with inhibitor 24 (4-(guanidinomethyl)phenylacetyl-Arg-Val-Arg-4-amidinobenzylamide) resulted in significantly delayed virus propagation compared with an inhibitor-free control. The same analog was also effective in inhibiting Shiga toxin activation in HEp-2 cells. This antiviral effect, as well as the protective effect against a bacterial toxin, suggests that inhibitors of furin or furin-like proprotein convertases could represent promising lead structures for future drug development, in particular for the treatment of infectious diseases.


Knowledge mapping of the links between the microbiota and allergic diseases: A bibliometric analysis (2002-2021).
In recent decades, dramatic changes in modern environmental exposures and lifestyles have resulted in a steep rise in the prevalence of allergic diseases such as asthma, allergic rhinitis, atopic dermatitis and food allergies. Evidence is mounting that the microbiota plays a crucial role in allergic disorder development and evolution. Therefore, a better understanding of allergic diseases within the context of the microbiota is urgently needed. This work aimed to comprehensively outline general characteristics, research hotspots, evolution routes, and emerging trends in this area. Relevant publications from January 2002 to December 2021 were obtained from the Web of Science Core Collection on 5 August 2022. Bibliometric and visual analyses were performed using CiteSpace; VOSviewer; an online bibliometric platform; and Microsoft Excel 2019. In total, 2535 documents met the requirements. The annual number of publications has shown rapid growth in the last two decades. The USA, University of California System, and Isolauri E of the University of Turku were the most productive and influential country, institution, and author, respectively. The Journal of Allergy and Clinical Immunology was the most prolific and most cocited journal. High-frequency keywords included "gut microbiota", "asthma", "atopic dermatitis", "children", and "probiotics". Recent studies have focused on "atopic dermatitis", "skin", "asthma", and "probiotics", according to the cocitation analysis of references. Burst detection analysis of keywords showed that "community", "skin microbiome", "microbiome", "Staphylococcus aureus", and "chain fatty acid" were emerging research frontiers, which currently have ongoing bursts. In the last 20 years, studies of the microbiota in allergic diseases have been flourishing, and the themes have been increasing in depth. These findings provide valuable references on the current research hotspots and gaps and development trends in the link between the microbiota and allergic diseases.


Venting during venoarterial extracorporeal membrane oxygenation.
Cardiogenic shock and cardiac arrest contribute pre-dominantly to mortality in acute cardiovascular care. Here, veno-arterial extracorporeal membrane oxygenation (VA-ECMO) has emerged as an established therapeutic option for patients suffering from these life-threatening entities. VA-ECMO provides temporary circulatory support until causative treatments are effective and enables recovery or serves as a bridging strategy to surgical ventricular assist devices, heart transplantation or decision-making. However, in-hospital mortality rate in this treatment population is still around 60%. In the recently published ARREST trial, VA-ECMO treatment lowered mortality rate in patients with ongoing cardiac arrest due to therapy refractory ventricular fibrillation compared to standard advanced cardiac life support in selected patients. Whether VA-ECMO can reduce mortality compared to standard of care in cardiogenic shock has to be evaluated in the ongoing prospective randomized studies EURO-SHOCK (NCT03813134) and ECLS-SHOCK (NCT03637205). As an innate drawback of VA-ECMO treatment, the retrograde aortic flow could lead to an elevation of left ventricular (LV) afterload, increase in LV filling pressure, mitral regurgitation, and elevated left atrial pressure. This may compromise myocardial function and recovery, pulmonary hemodynamics-possibly with concomitant pulmonary congestion and even lung failure-and contribute to poor outcomes in a relevant proportion of treated patients. To overcome these detrimental effects, a multitude of venting strategies are currently engaged for both preventive and emergent unloading. This review aims to provide a comprehensive and structured synopsis of existing venting modalities and their specific hemodynamic characteristics. We discuss in detail the available data on outcome categories and complication rates related to the respective venting option.


A new understanding of the microstructure of soot particles: The reduced graphene oxide-like skeleton and its visible-light driven formation of reactive oxygen species.
The mechanisms of soot's photochemistry are still unclear, especially, how the microstructure and composition of soot influence its photoactivity. In the current study, we started with the exploration of the microstructure of soot particles and gained new insights. The elemental-carbon fraction of soot (E-soot), considered the core component of soot and can reflect the intrinsic characteristics of soot, was extracted by organic solvents and characterized in terms of structure and chemical reactivity. The intrinsic structure of E-soot was found to be more analogous to reduced graphene oxide than to graphene, in terms of containing similar levels of defective sites such as oxygen-containing functional groups and environmentally persistent free radicals, as well as exhibiting similar optoelectronic performance. The generation of reactive oxygen species via an electron transfer pathway under visible light suggests that reduced graphene oxide-like E-soot can serve as a potential carbo-photocatalyst, which facilitates elucidating the mechanism of E-soot's role during soot's photochemical aging. Our study reveals the intrinsic structure of soot and its role in photo-triggered reactive oxygen species production, which is vital for atmospheric and health effects.


Empirical Comparison and Analysis of Web-Based DNA N 4-Methylcytosine Site Prediction Tools.
DNA N 4-methylcytosine (4mC) is a crucial epigenetic modification involved in various biological processes. Accurate genome-wide identification of these sites is critical for improving our understanding of their biological functions and mechanisms. As experimental methods for 4mC identification are tedious, expensive, and labor-intensive, several machine learning-based approaches have been developed for genome-wide detection of such sites in multiple species. However, the predictions projected by these tools are difficult to quantify and compare. To date, no systematic performance comparison of 4mC tools has been reported. The aim of this study was to compare and critically evaluate 12 publicly available 4mC site prediction tools according to species specificity, based on a huge independent validation dataset. The tools 4mCCNN (Escherichia coli), DNA4mC-LIP (Arabidopsis thaliana), iDNA-MS (Fragaria vesca), DNA4mC-LIP and 4mCCNN (Drosophila melanogaster), and four tools for Caenorhabditis elegans achieved excellent overall performance compared with their counterparts. However, none of the existing methods was suitable for Geoalkalibacter subterraneus, Geobacter pickeringii, and Mus musculus, thereby limiting their practical applicability. Model transferability to five species and non-transferability to three species are also discussed. The presented evaluation will assist researchers in selecting appropriate prediction tools that best suit their purpose and provide useful guidelines for the development of improved 4mC predictors in the future.


Exploring a parent-focused physical literacy intervention for early childhood: a pragmatic controlled trial of the PLAYshop.
Parents play a key role in young children's physical activity and physical literacy development. Little research has explored parent-focused interventions to improve young children's physical literacy. We examined if a theory-based, feasible physical literacy training workshop (PLAYshop) for parents could improve their physical literacy knowledge and confidence and improve parenting practices related to facilitating the physical literacy development of their preschool-aged child (3-5 years). The secondary objective was to explore implementation facilitators and barriers. We conducted a pragmatic controlled trial in two Canadian cities (Edmonton and Victoria) from November 2019 - March 2020. A total of 143/151 parents were eligible and assigned to intervention (n = 71) or control group (n = 72). The PLAYshop included: (i) a 75-min in-person workshop with interactive activities and physical literacy educational messages, (ii) educational materials, (iii) an equipment pack, and (iv) two post-workshop booster emails. Surveys measured parents' knowledge and confidence at baseline and follow-up. Application of PLAYshop concepts and implementation facilitators and barriers were explored with interviews of parents and workshop leaders. Repeated measures ANOVAs and thematic analyses were completed. Parents' knowledge and confidence improved significantly over time; intervention group changes were significantly greater than control group changes (p < 0.001; ɳ2 = .32). Parents applied PLAYshop concepts at-home, including child-led play, making activities fun, and promoting child manipulative and locomotor skills. Time was a key parental implementation barrier. Program implementation issues varied by context (location and participants). PLAYshop participation changed parents' physical literacy knowledge and confidence and physical literacy enhancing play with their children. Implementation feasibility was high. The findings from this real-world trial highlight an efficacious and scalable intervention that warrants further testing. ClinicalTrials.gov: NCT04394312 . Registered 19/05/2020.


Development of a potassium-based soil washing solution using response surface methodology for efficient removal of cesium contamination in soil.
The overuse of chelating soil washing agents for removal of heavy metal can release soil nutrients and negatively affect organisms. Therefore, developing novel washing agents that can overcome these shortcomings is necessary. In this study, we tested potassium as a main solute of novel washing agent for cesium-contaminated field soil, owing to the physicochemical similarities between potassium and cesium. Response surface methodology was combined with a four-factor, three-level Box-Behnken design to determine the superlative washing conditions of the potassium-based solution for the removal of cesium from the soil. The parameters that were considered were the following: potassium concentration, liquid-to-soil ratio, washing time, and pH. Twenty-seven sets of experiments were conducted using the Box-Behnken design, and a second-order polynomial regression equation model was obtained from the results. Analysis of variance proved the significance and goodness of fit of the derived model. Three-dimensional response surface plots displayed the results of each parameter and their reciprocal interactions. The washing conditions that achieved the highest cesium removal efficiency (81.3%) in field soil contaminated at 1.47 mg/kg were determined to be the following: a potassium concentration of 1 M, a liquid-to-soil ratio of 20, washing time of 2 h, and a pH of 2.


IL-34 is a potential biomarker for the treatment of papillary thyroid cancer.
Interleukin (IL)-34 is a recently discovered pro-inflammatory cytokine and is a vital regulator in different tumor types. However, the function of IL-34 in thyroid carcinoma has yet to be investigated. In this study, we analyzed the expression of IL-34 in human papillary thyroid cancer (PTC) samples and determined its effects on the proliferation and apoptosis of PTC cells. We examined the expression of IL-34 in serum and tissue samples of patients with PTC by Western blotting and ELISA assay and analyzed its association with clinicopathological features including tumor size, tumor node metastasis (TNM) stage, and lymph node metastasis (LNM). We selected TPC1 and K1 for knockdown or overexpressing of IL-34 via small interference RNA transfection. The proliferation of PTC cells was evaluated by CCK8 assay. We further investigated the role of IL-34 in apoptosis by flow cytometry and studied the protein levels of epithelial-mesenchymal transition (EMT) biomarkers, phosphorylated extracellular-regulated kinase (ERK), and total-ERK (t-ERK) by Western blotting. Our results show that IL-34 is significantly upregulated in serum and tissue samples from patients with PTC. IL-34 promotes the proliferation and suppresses apoptosis in PTC cells. In addition, IL-34 can promote the EMT and activate ERK signaling pathway in PTC cells. This study provides novel evidence that IL-34 serves as an oncogene in PTC. IL-34 promotes proliferation, EMT phenotype, and ERK signaling pathway and inhibits apoptosis in PTC cells. Therefore, IL-34 may be a potent therapeutic target for the treatment of PTC.


Highly stretchable composites based on cellulose.
Cellulose is a kind of natural polymer with good biocompatibility, biodegradability, non-toxicity, low cost and other advantages, which has been widely used in many fields, such as energy, biological scaffolds, medicine, paper making, cosmetics, and template materials. Based on this, how to use cellulose to construct stretchable composites to meet the needs of different fields has attracted widespread attention. In this review, we have described the applications of cellulose-based stretchable composites, including sensor applications, energy applications, bionic and medical materials applications, fabric applications, and packaging applications. Finally, the future development of stretchable composites based on cellulose is discussed.


Influence of bulking agents on organic matter evolution during sewage sludge composting; consequences on compost organic matter stability and N availability.
The influence of bulking agents on organic matter (OM) stability and nitrogen (N) availability in sludge composts was investigated. Seven mixtures were composted over a 12-week period in 170 L-reactors using the same sludge with different bulking agent mixtures. The OM evolution was characterised by carbon (C) and N mass balances in biochemical fractions. The evolution of OM stability and N potential availability were measured during soil incubations. The type of bulking agent had little influence on the intensity of OM stabilisation and the N availability in final composts. However, they influenced the time to reach similar OM stability and the biochemical evolution of OM. Depending on their ligno-cellulosic characteristics and a careful control of aeration, initial mixtures with high C:N ratio and rather biodegradable carbonaceous materials could favour the organisation of initially present mineral N or easily mineralisable sludge N and therefore limit NH3 volatilisation responsible for the low compost N availability measured.


Giant colon polyp in a child with suspected inflammatory bowel disease: US findings.
A 6-year-old boy with a history of diarrhea and rectal bleeding was referred to our department where he underwent ultrasound (US) examination for suspected inflammatory bowel disease. US showed the presence of an echoic oval mass measuring about 30 × 24 mm located at the transition between the transverse and descending colon. It moved with the peristaltic waves and was attached to the intestinal wall through a pedicle. Color Doppler showed intralesional blood flow. On the basis of these findings, the patient was suspected of having a colon polyp. This diagnosis was confirmed at subsequent colonoscopy. The mass was removed using a diathermy snare, and histologic examination revealed hamartomatous polyp measuring 32 mm.


Prevention of CeCl3-induced hepatotoxicity by hypolipidemic compounds.
Pretreatment of rats with nafenopin, a hypolipidemic compound, prevents the lethality and hepatotoxicity induced by cerium chloride (CeCl3), a rare earth metal. The increase in hepatic triglycerides and the morphologic changes observed after 48 h of the CeCl3 injection (10 mg/kg) are completely abolished by nafenopin given for 4 days in doses of 250 mg/kg. However, an increase in the frequency of peroxisomes is noted in rats receiving nafenopin and CeCl3, attributable to the hypolipidemic drug pretreatment. In comparing the protective effect of nafenopin with that of CPIB (a structurally related compound) and lentysine (a structurally unrelated agent), it can be seen that nafenopin is about five times more active in decreasing liver triglycerides. The hepatic ultrastructure of rats pretreated with CPIB or lentysine is similar to that of CeCl3-treated controls.


L-arginine increases nitric oxide and attenuates pressor and heart rate responses to change in posture in sickle cell anemia subjects.
Pressor and heart rate changes following change in posture without or with L-arginine supplementation (1g/day for 6 weeks) were studied in 28 sickle cell anemia (SCA) and 32 non-sickle cell anemia (NSCA) subjects. Change in posture increased HR (p<0.01), RPP (p<0.05) in both groups of subjects, MABP (p<0.05) in SCAS but reduced MABP (p<0.01) in NSCAS and PP (p<0.01) in SCAS. L-Arginine supplementation increased plasma L-Arginine concentration ([R]) in both groups of subjects (p<0.001 in each group) and serum nitric oxide metabolites concentration ([NOx]) (p<0.01 in each group). Change (Δ) [R] correlated positively with Δ [NOx] in both groups (+ 0.7 in each group). L-Arginine supplementation caused greater reduction of MABP (p<0.001) in NSCAS than in SCAS. However, reduction in HR was greater (p<0.001) in SCAS than in NSCAS. After supplementation, MABP and PP responses to change in posture were attenuated in the two groups. However, while HR and RPP responses in SCAS were attenuated, the same responses were enhanced in NSCAS by change in posture after supplementation. In conclusion, study shows that oral, low dose, chronic supplementation with L-arginine increased NO availability and attenuated pressor and heart rate responses to change in posture in sickle cell anemia subjects.


Cobalt as a gastric juice volume marker: comparison of two methods of estimation.
We investigated the use of cobalt-EDTA, a novel, nonabsorbable liquid phase marker, in the estimation of secretory volumes during topical misoprostol (synthetic PGE, analog) administration in the canine chambered gastric segment. We compared atomic absorption spectrophotometry (AAS) and instrumental neutron activation analysis (INAA) in the estimation of [Co]. Mucosal bathing solutions containing cobalt-EDTA were instilled into and recovered from the chamber by gravity every 15-min period as follows: (i) basal--60 min; (ii) misoprostol periods--150 min (plus 0.1-, 1-, 10-, 100-, and 1000-micrograms doses of misoprostol for two periods per dose). The recovered solutions were analyzed for [Co] by AAS and INAA. Total cobalt recovery by AAS after chamber washout was 102.97 +/- 0.98%. Mean +/- SE volumes (12.14 +/- 0.33 and 13.24 +/- 0.60 ml/15 min) obtained respectively from AAS and INAA were significantly higher (P less than 0.001) than the recovered mean volumes (10.51 +/- 0.17 ml/15 min). The percentage error in volume collection increased (range: 9.3-52.7%) with the volume of secretion. Values of [Co] obtained by the two techniques were comparable and not significantly different from each other (P greater than 0.05). INAA-estimated mean +/- SE [Co] showed consistently higher coefficients of variation. Spectra obtained for all samples during INAA measurements showed significant Compton background activity from 24Na and 38Cl. Cobalt-EDTA did not grossly or histologically damage the gastric mucosa. We conclude that cobalt is not adsorbed, absorbed, or metabolized, and is a suitable and reliable volume marker in this model.(ABSTRACT TRUNCATED AT 250 WORDS)


Portal arteriovenous fistula following partial gastrectomy.
An emergency transthoracic transection of the esophagus was performed on a 62 year old man for hematemesis caused by rupture of esophageal varices. Hepatic functional reserve of this patient was classified as Child C. Postoperative celiac arteriography revealed an arteriovenous fistula between a branch of the gastroduodenal artery and a branch of the superior mesenteric vein. He had undergone a partial gastrectomy with Billroth II reconstruction 15 years earlier. Bleeding from the esophageal varices did not recur, but he subsequently died of liver failure. In some areas of the liver the microscopic changes were similar to those occurring in cirrhosis, but in most areas they resembled those seen in congestive liver fibrosis. This case suggested that portal arteriovenous fistula is an important predisposing cause leading to deterioration of liver function.


Blockade of lymphotoxin pathway exacerbates autoimmune arthritis by enhancing the Th1 response.
To study the role of the lymphotoxin (LT) signaling pathway in the development and pathogenesis of collagen-induced arthritis (CIA), and to understand the mechanisms by which blockade of the LT pathway influences the arthritogenic response to type II collagen (CII). LTalpha-deficient and wild-type C57BL/6 mice were immunized with CII. Male DBA/1 mice were immunized with CII and treated with LTbeta receptor immunoglobulin fusion protein (LTbetaR-Ig) or control Ig. Mice were monitored for the development and severity of arthritis. The effects of LT blockade on immune responses were evaluated by cytokine production and antigen-specific proliferation in vitro, the delayed-type hypersensitivity (DTH) response, and serum levels of CII-specific antibodies. CIA that developed in LTalpha-deficient mice was more severe and prolonged than that which developed in wild-type mice. Blocking LT signaling with LTbetaR-Ig significantly exacerbated the disease. Exacerbation of CIA was associated with an enhanced Th1-type response, including increased type 1 cytokine production, an enhanced DTH response, and elevated production of CII-specific IgG2a antibodies. Blockade of the LT signaling pathway exacerbates the development and progression of CIA, probably by skewing the Th1/Th2 balance that determines the outcome of autoimmune responses.


Mechanisms for successful management of enterprise resource planning from user information processing and system quality perspective.
Enterprise resource planning (ERP) systems are now ubiquitous in modern organizations. A number of previous studies have focused only on system factors and perceptions, there is a noticeable shortfall in research that concurrently addresses technological factors and human roles in explaining user satisfaction. This study aimed to identify these variables from the perspectives of information systems, technology, and human participation, thereby addressing this knowledge gap. The focus of the study was a large shipbuilding and marine company utilizing an ERP system. The participants, a sample of 234 ERP users, were carefully selected by the company's executives and practitioners, and data was collected through online questionnaires. They were selected through purposive sampling from among employees who use ERP systems in large-scale shipbuilding and marine engineering companies. The study aimed to clarify the relationships between user satisfaction and perceived ease of use, perceived usefulness, system quality, service quality, participation, and information quality. A partial least squares structural equation modeling (PLS-SEM) was used to analyze the collected data. The results indicated that perceived ease of use, system quality, service quality, and participation positively influenced user satisfaction, whereas perceived usefulness did not have a significant impact. Interestingly, participation was found to lessen the effects of perceived usefulness on satisfaction. The findings of this study suggest that to enhance ERP user satisfaction, managers should strive to make the ERP system easy-to-use and stable, encourage employee participation in the decision-making process, and bolster the role of the support team. It should be noted, however, that the study has limitations as it did not consider all possible factors, such as training and support. Future research should take a broader view of the variables involved in the operation of an enterprise-wide information system.


Determination of purity values of amino acid reference materials by mass balance method: an approach to the quantification of related structure impurities.
A systematic procedure for the determination of purity values of amino acid reference materials was developed by use of mass balance method where four categories of impurities (related structure impurities (RSIs), water, organic solvent residue (OSR), and non-volatile residue (NVR)) were quantified separately. The amount of RSIs was determined using a combination of three quantification methods. To ensure metrological traceability in the determination of RSIs, at least one such impurity in each candidate amino acid reference material was quantified using liquid chromatography-isotope dilution tandem mass spectrometry (LC-IDMS/MS). Other RSIs were determined using external calibration liquid chromatography-tandem mass spectrometry (LC-MS/MS) or o-phthaldialdehyde (OPA) derivatization, followed by liquid chromatography-ultraviolet (LC-UV) measurement. As the UV absorption of most RSIs came basically from the same chromophore after OPA derivatization, a relative peak area approach was used in the LC-UV method to quantify the amount of RSIs by comparing their peak areas with that of a reference RSI. The reference RSI was pre-selected and the amount determined by LC-IDMS/MS separately. The absence of D-amino acids was confirmed using Marfey's reagent derivatization, followed by LC-UV analysis. The amounts of water, OSR, and NVR were measured using Karl Fischer coulometry, gas chromatography-mass spectrometry (GC-MS) and thermogravimetry, respectively. By using this procedure, four amino acid (L-valine, L-leucine, L-isoleucine, and L-phenylalanine) certified reference materials (CRMs) were developed from the candidate materials. The homogeneity and stability of the CRMs were demonstrated by use of LC-IDMS/MS or OPA-LC-UV method, following the principles in ISO 17034 and ISO Guide 35.Graphical abstract.


Direct determinations of energetic parameters at chitosan/Cr(VI) interfaces by means of immersion heat-conduction microcalorimetry.
Interaction parameters at epichlorohydrin-crosslinked chitosan beads/Cr(VI) interfaces from aqueous solutions was obtained by using immersion heat-conduction microcalorimetry. This technique permits simultaneous determinations of adsorbed amounts and interaction energies. The experimental variables evaluated were pH of the Cr(VI) solutions of 4.0 and 6.0, initial Cr(VI) concentration in solution of 0.50 and 5.00 × 10(-3) mol L(-1) and temperature of 25 and 45 °C. The calorimetric results were evaluated using a 2(3) full factorial design. The responses were the adsorption amounts (n(int)), the adsorption energies (Q(int)) and the adsorption enthalpies (Δ(int)H). The results indicated that all thermodynamic responses (adsorption energies and adsorption enthalpies) are all exothermic in nature. The initial Cr(VI) concentration in solution was the most important parameter in all responses evaluated in this study. Polynomial fits have pointed out that almost all interactive effects are statistically important on the values of n(int), Q(int) and Δ(int)H. It is concluded that the thermodynamical aspects of the Cr(VI) adsorption parameters are greatly influenced by the interactive factors and not by temperature changes alone.


Higher intuitive eating is associated with lower adiposity in midlife women.
Intuitive eating (IE) is consistently associated with a lower body mass index, though its relationship with adiposity, specifically abdominal adiposity, is unknown. Given that midlife women often experience increases in adiposity during midlife, our objective was to examine the association between IE and adiposity in midlife women. We also aimed to validate the factor structure of the Intuitive Eating Scale (IES) in a sample of midlife women. We analyzed data from a cross-sectional study of 116 women between 40 and 64 years of age. Participants completed in-person visits and self-reported questionnaires, including the 21-item IES. Adiposity was assessed using dual energy x-ray absorptiometry. Measurements included total body fat percentage and android/gynoid (AG) ratio as a measure of abdominal adiposity. Confirmatory factor analysis of the IES demonstrated a poor fit to the data. Thus, we conducted an exploratory factor analysis which resulted in a 15-item scale with five items on each subscale, and demonstrated improved fit. Higher intuitive eating was associated with lower total body fat percentage (β = -6.77, p < 0.0001) and lower abdominal adiposity (β = -0.09, p = 0.0005). Higher scores on eating for physical reasons and reliance on internal hunger and satiety cues were associated with lower total body fat and lower abdominal adiposity. Our findings suggest that higher intuitive eating is associated with lower total body fat percentage and lower abdominal adiposity. These results may have public health implications to promote intuitive eating in midlife women, a population at risk of weight gain and changes to body fat distribution.


Sexual discrimination in neurosurgery: a questionnaire-based nationwide study amongst women neurosurgeons in Bulgaria.
The aim of this qualitative, descriptive, cross-sectional study was to identify potential factors influencing the progression of female neurosurgeons in Bulgaria. The study was conducted nationally, by sending out an online (SurveyMonkey®) questionnaire with 30 questions over a 3-month period to 15 registered female neurosurgeons in practice including residents/trainees and specialists from state universities, private universities and regional hospitals in Bulgaria. The questionnaire covered basic demographics, level of academic achievement and aspects of personal and professional experience, along with questions on the perceived barriers that female neurosurgeons nationally encountered during their clinical and academic career. These results were compared with similar studies conducted in other countries following a literature search on PubMed. Eleven out of fifteen respondents returned the completed survey, covering 10 institutions which included 8 university clinics and two regional clinics, achieving a response rate of 73.3%. No questionnaires were excluded. The factors negatively influencing the clinical and academic professional development and progression in the field included lack of mentors and other female role models, perceived bias regarding remuneration and leave, as well as a lack of support with regards to work-life balance and difficulty progressing in the academic fields. Although there is an ever increasing and growing awareness of the factors negatively impacting women progression in neurosurgery worldwide, there are still significant gaps and biases that hinder career progression amongst female neurosurgical communities and highlight a need for potential practices to be established in the workplace to counteract this.


Studies of enzymuria and beta 2-microglobulinuria in patients receiving prophylactic cefotaxime in obstetric and gynaecological surgery.
Increased urinary excretion of beta 2-microglobulin and certain enzymes, for example leucine aminopeptidase (LAP) and N-acetyl-beta-D-glucosaminidase (NAG), produces sensitive markers of damage to renal tubular cells. These markers were monitored in patients undergoing obstetric and gynaecological surgery who received cefotaxime for 5 days. Slight increased activity in NAG and beta 2-microglobulin was observed in some patients 3 to 5 days after surgery. However, no changes of significance were found in levels of urinary LAP and NAG. During cefotaxime treatment, urinary beta 2-microglobulin in the group of abdominal hysterectomy increased slightly. In most cases renal side effects are negligible and cannot be detected by these tests. These results indicate that administration of cefotaxime in obstetric and gynaecological surgery does not produce cumulative renal tubular toxicity.


Systematic Review and Meta-Analysis: Epidemiology of Human Blastocystis spp. Infection in Malaysia.
Blastocystis spp. is a unicellular enteric protozoan parasite in humans with a controversial role in disease etiology. It is common in developing countries among immunocompromised patients and people who have close contact with animals. In this study, we have systematically reviewed previous studies on the distribution and genotypes of human Blastocystis infection in Peninsular Malaysia. Studies examining the prevalence of Blastocystis in diverse demographics, including rural, urban, comorbid conditions, and high-risk populations, were taken into consideration. The infection has been reported in nine states; the total percentage of infection was 17.8% (1671/9397), with the most cases in Pahang (27.3%) and the least in Johor (3.4%). Molecular studies revealed the presence of six subtypes: ST1, ST2, ST3, ST4, ST5, and ST6. ST3 was reported as the predominant subtype in all the states, with a prevalence of 54.7% (338/618). The findings provide greater clarity on the epidemiology of Blastocystis in Malaysia, which will help in policy making towards planning and strategizing control measures against the parasite.


Exploring the role of LC-PUFA metabolism in pregnancy complications.
Maternal nutrition during pregnancy plays a significant role in growth and development of the placenta and influencing pregnancy outcome. Suboptimal nutritional status during early gestational period compromises the normal course of pregnancy leading to adverse maternal and fetal outcomes. Omega-3 and omega-6 long chain polyunsaturated fatty acids (LC-PUFA) are important for the growth and development of the placenta. Maternal fatty acids and their metabolites influence the normal course of pregnancy by regulating cell growth and development, cell signaling, regulate angiogenesis, modulate inflammatory responses and influence various structural and functional processes. Alterations in LC-PUFA and their metabolites may result in inadequate spiral artery remodeling or placental angiogenesis leading to structural and functional deficiency of the placenta which contributes to several pregnancy complications like preeclampsia, gestational diabetes mellitus, intrauterine growth restriction, and results in adverse birth outcomes. In this review, we summarize studies examining the role of fatty acids and their metabolites in pregnancy. We also discuss the possible molecular mechanisms through which LC-PUFA influences placental growth and development. Studies have demonstrated that omega-3 fatty acid supplementation lowers the incidence of preterm births, but its effect on reducing pregnancy complications are inconclusive.


Deltamycins, new macrolide antibiotics. II. Isolation and physicochemical properties.
The new macrolide antibiotics were isolated by silica gel chromatography. They showed a UV absorption maximum at 240 nm. Deltamycins A1, A2 and A3 were demonstrated to be new macrolide antibiotics on the basis of their physicochemical properties whereas deltamycin A4 was identified as carbomycin A.


Analysis of Secreted MIF from Cultured Murine Bone Marrow-Derived Immune Cells.
Macrophage migration inhibitory factor (MIF) is expressed and released ubiquitously by numerous cell types and tissues. MIF is detected and constitutively expressed at the protein level both intra- and extracellularly. This chapter outlines methods for cultivating, purifying, detecting, and quantifying concentrations of MIF from murine primary derived macrophages and dendritic cell culture supernatants.


Low viral load of Merkel cell polyomavirus in Iranian patients with head and neck squamous cell carcinoma: Is it clinically important?
Recent studies show that the human Merkel cell polyomavirus (MCPyV) may be involved in causing cancer. The objective of this study was to assess the impact of MCPyV on the development of head and neck squamous cell carcinoma (HNSCC). In total, 50 paraffin-embedded HNSCC biopsy samples and 50 adjacent non-cancerous samples were evaluated for the presence of MCPyV DNA and RNA. Among patients, the five most frequent histopathologic sites were the tongue (22.0%), lip (16.0%), submandibular (14.0%), cheek (14.0%), and throat (14.0%). MCPyV DNA was positive in eight (16.0%) samples. The median MCPyV LT-Ag copy number in the eight positive samples and in one non-cancerous sample was 4.8 × 10-3 and 2.6 × 10-5 copies/cell, respectively. Quantification of MCPyV LT-Ag revealed increased expression in stage III (5.6 × 10-3 copies/cell) than in the other stages. The MCPyV DNA load in different stages of HNSCC was also statistically significant (P = 0.027). The viral load was low, suggesting that only a fraction of cancerous cells is infected. This result provides evidence confirming the presence of MCPyV in a subset of Iranian patients with HNSCCs, but further studies needed to confirm our findings.


Mechanistic implications of the inhibition of peptidases by amino aldehydes and bestatin.
alpha-Amino aldehydes and bestatin are found to be effective inhibitors of a cytosolic dipeptidase (rat testicular peptidase C), and a cytosolic tripeptidase (rat kidney peptidase B, EC 220.127.116.11), as well as cytosolic leucine aminopeptidase (pig kidney peptidase S, EC 188.8.131.52). Aldehyde hydrates and bestatin share a resemblance to intermediates that might be formed during direct attack by water on peptide substrates, affording a possible explanation for their tight binding. Alternatively, inhibitors of both kinds might form derivatives of an active site nucleophile, resembling intermediates in a double-displacement mechanism. Exchange experiments with H218O suggest that bestatin is bound intact by leucine aminopeptidase, lending support to the first of these two mechanisms.


[Effect of RbAp48 knockdown on migration and invasion of human cervical cancer cell line MS751 in vitro].
To investigate the effect of RbAp48 knockdown on the migration and invasion of human cervical cancer cells and explore the mechanism. A small interference RNA (siRNA) was used to knock down the expression of RbAp48 in MS751 cells. The changes in cell migration and invasion were evaluated using wound healing assay and Transwell assay, respectively, and the expressions of RbAp48, vimentin, N-cadherin, E-cadherin, Snail, Twist, MMP-2 and TIMP-2 were determined with Western blotting. After siRNA-mediated RbAp48 knockdown, MS751 cells showed a significantly reduced expression of RbAp48 with significantly suppressed cell migration and invasion (P<0.01). RbAp48 knockdown induced obvious down-regulation of the expressions of interstitial cell phenotype proteins vimentin, N-cadherin, and MMP-2 and up-regulation of epithelial cell phenotype proteins E-cadherin and TIMP-2, suggesting the inhibition of epithelial- mesenchymal transition of the cells. The expressions of Snail and Twist were significantly down-regulated in the cells following RbAp48 knockdown. Knockdown of RbAp48 can significantly inhibit epithelial-mesenchymal transition and suppress the migration and invasion of cervical cancer cell line MS751, the mechanism of which may involve the down-regulation of Snail and Twist expressions.


Clinical manifestations of human immunodeficiency virus-induced uveitis.
To describe the clinical manifestations of patients with human immunodeficiency virus (HIV)-induced uveitis in Thailand. Prospective cohort study of 6 patients with HIV-induced uveitis. Six patients (8 eyes) with HIV-induced uveitis who had an extremely high intraocular: plasma HIV-1 RNA ratio. The clinical manifestations and laboratory findings are reported of 6 consecutive patients with HIV-induced uveitis who had an extremely high intraocular-to-plasma HIV-1 RNA ratio and were diagnosed between July 2009 and May 2011. Clinical manifestations and laboratory findings. Human immunodeficiency virus-induced uveitis was diagnosed in 4 men and 2 women with an average age of 41 years at presentation. None of the patients were receiving highly active anti-retroviral therapy (HAART) or had clinical or laboratory evidence, or both, of opportunistic infections. The mean plasma load was 218 688 copies/ml (median, 137 500 copies/ml; range, 24 900-540 000 copies/ml), and the mean intraocular HIV load was 20 937 755 copies/ml (median, 7 499 000 copies/ml; range, 2 460 000-89 800 000 copies/ml). The average CD4 cell count was 192 cells/μl (median, 248 cells/μl; range, 5-342 cells/μl). All the patients had decreased vision, and none had conjunctival hyperemia. The anatomic location of uveitis was anterior in all patients, and associated vitreitis was present in 4 patients; none exhibited retinal lesions or scars. Anterior segment inflammation and keratic precipitates were observed in all patients, and none responded to topical corticosteroid therapy. After the administration of HAART, the intraocular inflammation disappeared entirely within several weeks in all of the patients and the intraocular and plasma HIV loads decreased. Human immunodeficiency virus-induced uveitis should be suspected in HAART-naïve, HIV-positive patients or in those in whom this treatment fails and who have anterior uveitis without any retinal lesions and exhibit no response to topical corticosteroids. The concurrent determination of HIV load in the intraocular fluids and plasma may clarify the cause of HIV-associated uveitis.


High pressure induced charge transfer in 3d-4f bimetallic photomagnetic materials.
Pressure-induced crystal color change of photo-magnetic materials [Ln(DMF)4(H2O)3(μ-CN)M(CN)5]·H2O, Ln = Y, M = Fe (1), Ln = Y, M = Co (2), Ln = Nd, M = Fe (3) (DMF = N,N-dimethyl formamide) are investigated using variable pressure X-ray Absorption Near-Edge Structure (XANES) spectroscopy and X-ray diffraction. For 1 the effect is caused by ligand-to-metal charge transfer (LMCT) on the iron site.


Bcl-X(L) is a chemoresistance factor in human melanoma cells that can be inhibited by antisense therapy.
Malignant melanoma is a tumor that responds poorly to a variety of apoptosis-inducing treatment modalities, such as chemotherapy. The expression of genes that regulate apoptotic cell death plays an important role in determining the sensitivity of tumor cells to chemotherapeutic intervention. Bcl-x(L) is an antiapoptotic member of the Bcl-2 family and is universally expressed in human melanoma. To evaluate the Bcl-x(L) protein as a potential therapeutic target in melanoma, the influence of Bcl-x(L) expression levels on the chemoresistance of human melanoma cells was investigated. Overexpression of Bcl-x(L) in stably transfected human melanoma Mel Juso cells significantly reduced sensitivity to cisplatin-induced apoptosis (p < or = 0.05). In a parallel approach, reduction of Bcl-x(L) protein by specific AS oligonucleotide (ISIS 16009) treatment enhanced the chemosensitivity of Mel Juso cells by 62% compared to cells treated with MM control oligonucleotide (ISIS 16967) as well as chemotherapy-induced apoptosis. These data suggest that Bcl-x(L) is an important factor contributing to the chemoresistance of human melanoma. Reduction of Bcl-x(L) expression by AS oligonucleotides provides a rational and promising approach that may help to overcome chemoresistance in this malignancy.


A variant of neonatal progeroid syndrome, or Wiedemann-Rautenstrauch syndrome, is associated with a nonsense variant in POLR3GL.
Neonatal progeroid syndrome, also known as Wiedemann-Rautenstrauch syndrome, is a rare condition characterized by severe growth retardation, apparent macrocephaly with prominent scalp veins, and lipodystrophy. It is caused by biallelic variants in POLR3A, a gene encoding for a subunit of RNA polymerase III. All variants reported in the literature lead to at least a partial loss-of-function (when considering both alleles together). Here, we describe an individual with several clinical features of neonatal progeroid syndrome in whom exome sequencing revealed a homozygous nonsense variant in POLR3GL (NM_032305.2:c.358C>T; p.(Arg120Ter)). POLR3GL also encodes a subunit of RNA polymerase III and has recently been associated with endosteal hyperostosis and oligodontia in three patients with a phenotype distinct from the patient described here. Given the important role of POLR3GL in the same complex as the protein implicated in neonatal progeroid syndrome, the nature of the variant identified, our RNA studies suggesting nonsense-mediated decay, and the clinical overlap, we propose POLR3GL as a gene causing a variant of neonatal progeroid syndrome and therefore expand the phenotype associated with POLR3GL variants.


The prospective evaluation of risk factors and clinical influence of carbapenem resistance in children with gram-negative bacteria infection.
Carbapenem-resistant gram-negative (CRGN) infections have been increasing in recent years and associated with significant morbidity, mortality, and health care costs. The aim of this study was to evaluate the epidemiologic and clinical risk characteristics, risk factors, and outcome of CRGN infections and to compare with carbapenem-sensitive gram-negative (CSGN) infections in children. Newly diagnosed CRGN infections in hospitalized children younger than age 18 years were prospectively recorded and all patients infected with a CSGN pathogen in the same unit within 48 hours of diagnosis were included in a control group between April 1, 2014, and December 31, 2014. Twenty-seven patients with CRGN infections and 28 patients with CSGN infections were enrolled in this study. Ventilator-associated pneumonia was the most common type of infection in both groups. Prior exposure to carbapenems (relative risk [RR], 11.368; 95% confidence interval [CI], 1.311-98.589), prolonged hospitalization (RR, 5.100; 95% CI, 1.601-16.242) were found to be independent risk factors for acquiring CRGN infections. Septic shock was significantly more frequent in the CRGN group (RR, 9.450; 95% CI, 1.075-83.065). The in-hospital mortality was higher in the CRGN group (RR, 7.647; 95% CI, 1.488-39.290). Prior carbapenem exposure and prolonged hospitalization are the most important risk factors for acquiring CRGN infections in our hospital. This study demonstrated, similar to previous reports, that carbapenem resistance increases morbidity, mortality, and health care costs.


A new test of resistance in the diagnosis of postero-superior rotator cuff tears.
The aim of this study was to assess the diagnostic accuracy of a new clinical test for the diagnosis of subacromial impingement and full thickness postero-superior rotator cuff tears. One hundred and twenty patients who underwent arthroscopic treatment for acromioplasty or cuff repair were previously submitted to a new test of resistance. The test is performed in the standing position with the involved arm in 90 degrees abduction, 20 degrees -30 degrees anteposition and in external rotation (as for full-can test). Thus, the patient was invited to follow the way of a spiral drawn on a drawing sheet for 20 turns; 1 turn = from the centre to the end of the spiral and vice versa (spiral width = 20 cm). The test was considered positive when the patient was not able to conclude it due to strength decrease or to shoulder pain. Sensitivity, specificity, positive and negative predictive values as well as diagnostic accuracy were calculated for our test of resistance. The test resulted scarcely reliable as detector of subacromial impingement and not very reliable as detector of small tear. When the test is positive there is a high probability that a subacromial disease exists; instead, when it is negative there is a high probability that the patient has not a large or massive cuff tear. The resistance test (Gum-Turn test) adds to our armamentarium of physical examination signs in patients with painful shoulder and furnishes further information on possible dimensions of tendinous tear.


Tumor necrosis factor as a mediator of Mycoplasma orale-induced tumor cell lysis by macrophages.
We and other investigators have previously demonstrated that mycoplasmas induce macrophage-mediated lysis of tumor cells, but the mechanism responsible for this process had, thus far, not been clarified. We now report that addition of either viable or heat-killed Mycoplasma orale to murine macrophages induces a cytolytic activity which, due to its neutralization by a specific antiserum against murine cloned recombinant tumor necrosis factor (rTNF), was identified as TNF-mediated. Both thioglycollate-elicited peritoneal macrophages and the normal macrophages cloned from our JBM phi 1.1 bone-marrow-derived cell line effectively produced TNF at levels similar to, or higher than, those obtained in the presence of high concentrations of lipopolysaccharide (LPS). Four other mycoplasma species demonstrated a varied capacity to induce TNF production by macrophages. Elevated TNF levels were also observed during macrophage-mediated cytolysis of murine A9 fibrosarcoma cells in the presence of either M. orale or LPS. Addition of the specific antiserum against rTNF at a concentration which neutralized all TNF activity in the co-cultures partially inhibited concomitant A9 cell killing. We can, therefore, conclude that M. orale induces TNF production which is, at least partially, responsible for subsequent tumor cell killing.


[Treatment of a traumatic intestinal prolaps in a lizard (author's transl)].
A serious intestinal prolaps in a lizard (Lacerta pityusensis pityusensis) that was sent by parcel post package, was replaced and the wound sutured. Anaesthesia, surgery and post-operative course are described.


X chromosome inactivation analysis to distinguish sporadic cases of X-linked agammaglobulinaemia from common variable immunodeficiency.
The X chromosome inactivation analysis of eight female relatives was performed to elucidate the X chromosome gene defect of six male hypogammaglobulinaemic individuals. The patients had diminished numbers of circulating B-cells and no relevant family history. The methylation status of three X-linked genes, phosphoglycerate kinase, hypoxanthine phosphoribosyl transferase and DXS255, was determined on DNA from Epstein-Barr virus-transformed B-cell lines established from the female relatives. The methylation pattern of at least one gene was informative in all eight females examined. While both alleles were equally methylated in four of eight females, the remaining four female relatives of three hypogammaglobulinaemia patients exhibited a non-random methylation pattern in their B-cells, suggesting that these three patients represented sporadic cases of X-linked agammaglobulinaemia (XLA). The clinical or immunological status of these three patients did not differ from the remaining two who had early onset hypogammaglobulinaemia and who were tentatively diagnosed as having common variable immunodeficiency. The sixth patient had recurrent infections after undergoing surgical removal of a brain tumour at 22 years of age, although his immunological features did not distinguish him from the other patients. X chromosome inactivation analysis can be useful in differentiating XLA from hypogammaglobulinaemia in male patients.


The Geometry of Marked Contact Engel Structures.
A contact twisted cubic structure ( M , C , γ ) is a 5-dimensional manifold M together with a contact distribution C and a bundle of twisted cubics γ ⊂ P ( C ) compatible with the conformal symplectic form on C . The simplest contact twisted cubic structure is referred to as the contact Engel structure; its symmetry group is the exceptional group G 2 . In the present paper we equip the contact Engel structure with a smooth section σ : M → γ , which "marks" a point in each fibre γ x . We study the local geometry of the resulting structures ( M , C , γ , σ ) , which we call marked contact Engel structures. Equivalently, our study can be viewed as a study of foliations of M by curves whose tangent directions are everywhere contained in γ . We provide a complete set of local invariants of marked contact Engel structures, we classify all homogeneous models with symmetry groups of dimension ≥ 6 up to local equivalence, and we prove an analogue of the classical Kerr theorem from Relativity.


Amplification-mutagenesis: evidence that "directed" adaptive mutation and general hypermutability result from growth with a selected gene amplification.
When a particular lac mutant of Escherichia coli starves in the presence of lactose, nongrowing cells appear to direct mutations preferentially to sites that allow growth (adaptive mutation). This observation suggested that growth limitation stimulates mutability. Evidence is provided here that this behavior is actually caused by a standard Darwinian process in which natural selection acts in three sequential steps. First, growth limitation favors growth of a subpopulation with an amplification of the mutant lac gene; next, it favors cells with a lac(+) revertant allele within the amplified array. Finally, it favors loss of mutant copies until a stable haploid lac(+) revertant arises and overgrows the colony. By increasing the lac copy number, selection enhances the likelihood of reversion within each developing clone. This sequence of events appears to direct mutations to useful sites. General mutagenesis is a side-effect of growth with an amplification (SOS induction). The F' plasmid, which carries lac, contributes by stimulating gene duplication and amplification. Selective stress has no direct effect on mutation rate or target specificity, but acts to favor a succession of cell types with progressively improved growth on lactose. The sequence of events--amplification, mutation, segregation--may help to explain both the origins of some cancers and the evolution of new genes under selection.


Lasso procedure to revise overcorrection with radial keratotomy.
To report three patients who underwent the lasso procedure to revise overcorrection with radial keratotomy. Case report and review of the literature. Four eyes of three patients who had undergone radial keratotomy with resultant hyperopic overcorrection underwent a lasso procedure. Before the procedure, average cycloplegic refraction spherical equivalent was +3.656 +/- 1.352 diopters, and average manifest refraction spherical equivalent was +2.250 +/- 0.621 diopters. A 10.0 monofilament nylon suture was placed in a circumferencial manner through the corneal stroma and overlapping the old radial keratotomy incisions. At 1 month postoperatively, best-corrected visual acuity was 20/20 in all four eyes, with average cycloplegic refraction spherical equivalent +0.438 +/- 1.423 diopters and average manifest refraction spherical equivalent -0.156 +/- 1.147 diopters. Mean delta cycloplegic refraction spherical equivalent was 3.219 +/- 1.724. The lasso procedure provides an immediate solution for symptomatic overcorrected hyperopic eyes after radial keratotomy. Predictability and long-term stability necessitate further follow-up.


The microbial diversity of laboratory-scale wetlands appears to be randomly assembled.
This study investigated the formation of the microbial communities in two horizontal subsurface-flow laboratory-scale constructed wetlands, one planted and the other one unplanted. The abundance of the predominant functional groups (Archaea, Bacteria and sulphate-reducing bacteria) was determined using fluorescence in situ hybridization and the diversity and community structure of those functional groups were analysed using denaturing gradient gel electrophoresis. The numbers of Archaea, Bacteria and sulphate-reducing bacteria were indistinguishable in both reactors (P=0.99, 0.80 and 0.55, respectively). The microbial communities in both wetlands were typically no more similar than if they had been randomly assembled from a common source community. Plants did not appear to exert a strong effect on the structure of the microbial communities in the horizontal subsurface-flow constructed wetlands (HSCWs) studied in this investigation.


Myocardial perfusion during cardiopulmonary resuscitation (CPR): effects of 10, 25 and 50% coronary stenoses.
Myocardial blood flow under normal physiologic conditions remains relatively unaltered by coronary lesions with diameter stenosis of less than 70%. However, during cardiac arrest and cardiopulmonary resuscitation (CPR), autoregulation of coronary blood flow is compromised. We studied the effect of previously considered 'trivial' coronary stenoses of 10, 25 and 50% on distal myocardial perfusion in 39 swine undergoing CPR for cardiac arrest. Endocardial blood flow distal to the stenosis was significantly less than that proximal in all the different stenoses groups (P < 0.05). A 50% diameter stenosis also compromised epicardial blood flow distal to the stenosis (P < 0.05). This study suggests that any coronary lesion may compromise myocardial perfusion during CPR. Since the vast majority of cardiac arrest victims have coronary artery disease, careful attention to maximizing myocardial blood flow during CPR is needed.


Functional traits of plants and pollinators explain resource overlap between honeybees and wild pollinators.
Managed and wild pollinators often cohabit in both managed and natural ecosystems. The western honeybee, Apis mellifera, is the most widespread managed pollinator species. Due to its density and behaviour, it can potentially influence the foraging activity of wild pollinators, but the strength and direction of this effect are often context-dependent. Here, we observed plant-pollinator interactions in 51 grasslands, and we measured functional traits of both plants and pollinators. Using a multi-model inference approach, we explored the effects of honeybee abundance, temperature, plant functional diversity, and trait similarity between wild pollinators and the honeybee on the resource overlap between wild pollinators and the honeybee. Resource overlap decreased with increasing honeybee abundance only in plant communities with high functional diversity, suggesting a potential diet shift of wild pollinators in areas with a high variability of flower morphologies. Moreover, resource overlap increased with increasing trait similarity between wild pollinators and the honeybee. In particular, central-place foragers of family Apidae with proboscis length similar to the honeybee exhibited the highest resource overlap. Our results underline the importance of promoting functional diversity of plant communities to support wild pollinators in areas with a high density of honeybee hives. Moreover, greater attention should be paid to areas where pollinators possess functional traits similar to the honeybee, as they are expected to be more prone to potential competition with this species.


Targeting bromodomain-containing protein 4 (BRD4) inhibits MYC expression in colorectal cancer cells.
The transcriptional regulator BRD4 has been shown to be important for the expression of several oncogenes including MYC. Inhibiting of BRD4 has broad antiproliferative activity in different cancer cell types. The small molecule JQ1 blocks the interaction of BRD4 with acetylated histones leading to transcriptional modulation. Depleting BRD4 via engineered bifunctional small molecules named PROTACs (proteolysis targeting chimeras) represents the next-generation approach to JQ1-mediated BRD4 inhibition. PROTACs trigger BRD4 for proteasomale degradation by recruiting E3 ligases. The aim of this study was therefore to validate the importance of BRD4 as a relevant target in colorectal cancer (CRC) cells and to compare the efficacy of BRD4 inhibition with BRD4 degradation on downregulating MYC expression. JQ1 induced a downregulation of both MYC mRNA and MYC protein associated with an antiproliferative phenotype in CRC cells. dBET1 and MZ1 induced degradation of BRD4 followed by a reduction in MYC expression and CRC cell proliferation. In SW480 cells, where dBET1 failed, we found significantly lower levels of the E3 ligase cereblon, which is essential for dBET1-induced BRD4 degradation. To gain mechanistic insight into the unresponsiveness to dBET1, we generated dBET1-resistant LS174t cells and found a strong downregulation of cereblon protein. These findings suggest that inhibition of BRD4 by JQ1 and degradation of BRD4 by dBET1 and MZ1 are powerful tools for reducing MYC expression and CRC cell proliferation. In addition, downregulation of cereblon may be an important mechanism for developing dBET1 resistance, which can be evaded by incubating dBET1-resistant cells with JQ1 or MZ1.


Physical distancing for care delivery in health care settings: Considerations and consequences.
As health care systems explore new ways of delivering care for patients with and without COVID-19, they must consider how to maintain physical distancing among health care workers and patients. Physical distancing in high complexity systems such as health care is particularly challenging and may benefit from a human factors and systems engineering perspective. We discuss challenges to implementing and maintaining physical distancing in health care settings and present possible solutions from a human factors and systems engineering perspective.


Ultrastructure of the human antral G cells during fasting.
The ultrastructure of the human antral G cells was examined in gastrobiopsies of 7 healthy volunteers fasting 24 to 240 hours. In contrast to the animals gastric C cells during fasting, the dissolution of the substance of gastrin granules (but not emiocytosis of granules) was observed in the human antral G cells during long fasting. The authors consider the possibility of artificially inducing the dissolution of the substance of the granules only the technique of gastrobiopsy itself.


Comparable morphometric data of pathological nerve obtained using the three-window sampling method and total fiber quantification.
Morphometric analysis of nerve biopsy provides data of structural changes that are essential for early detection of peripheral neuropathy. Because of the laborious work associated with the total fiber quantification, various sampling methods have been introduced with controversial accuracy. Three-window sampling technique has been recently proposed to provide the accurate morphometric data of normal human sural nerve. However, its application in the diseased nerve has not been validated. This study, therefore, compared the morphometric data of nerve biopsies from 12 patients with various neuropathies obtained using this sampling method and those obtained by total fiber analysis. Total number, density, and diameter of myelinated fibers including myelin thickness and g ratio were analyzed. Intraclass correlation coefficients ranging from 0.95 to 0.99 indicate the high agreement between the data derived from the two methods in these parameters. This finding suggests the accuracy of the three-window sampling technique in the morphometric study of nerve with pathological alterations.


Solitary and multiple resected adenocarcinomas after CT screening for lung cancer: histopathologic features and their prognostic implications.
To study the histopathologic features of CT screen-detected Stage IA adenocarcinomas to determine whether survival differed by the proportion of bronchioloalveolar component (BAC) or by the presence of multiple lesions in node-negative patients. Five pathologists with expertise in pulmonary pathology examined 279 resected cases of adenocarcinomas, 30 mm or less in length diagnosed by CT screening for lung cancer. The panel determined the consensus diagnosis for each case, identified additional cancers, and classified each case as solitary or non-solitary. The presence and proportion of BAC was also documented. Of the cases of adenocarcinoma, 20 (7%) were BAC subtype, 246 (88%) mixed subtype and 13 (5%) adenocarcinoma-OTHER. BAC cases manifested as non-solid and part solid nodules, mixed as solid and part-solid, and other as solid only. Kaplan-Meier 10-year survival rates were 100% for BAC and adeno-MIXED with 90-99% BAC cases, 95% for mixed with 1-90% BAC, 90% for those without a BAC component, and 75% for other cases. Fifty (18%) cases were non-solitary carcinomas and 44 of these were node negative; the non-solitary node-negative cases had the same excellent prognosis as solitary node-negative cases. The proportion of BAC component was a positive prognostic factor and correlated with CT consistency. Contrary to staging predictions, cases of non-solitary node-negative adenocarcinoma had the same excellent prognosis as solitary node-negative cases, suggesting that most of the small, node-negative multiple carcinomas probably represent multiple primaries rather than intrapulmonary metastasis.


Selective binding of retrotransposons by ZFP352 facilitates the timely dissolution of totipotency network.
Acquisition of new stem cell fates relies on the dissolution of the prior regulatory network sustaining the existing cell fates. Currently, extensive insights have been revealed for the totipotency regulatory network around the zygotic genome activation (ZGA) period. However, how the dissolution of the totipotency network is triggered to ensure the timely embryonic development following ZGA is largely unknown. In this study, we identify the unexpected role of a highly expressed 2-cell (2C) embryo specific transcription factor, ZFP352, in facilitating the dissolution of the totipotency network. We find that ZFP352 has selective binding towards two different retrotransposon sub-families. ZFP352 coordinates with DUX to bind the 2C specific MT2_Mm sub-family. On the other hand, without DUX, ZFP352 switches affinity to bind extensively onto SINE_B1/Alu sub-family. This leads to the activation of later developmental programs like ubiquitination pathways, to facilitate the dissolution of the 2C state. Correspondingly, depleting ZFP352 in mouse embryos delays the 2C to morula transition process. Thus, through a shift of binding from MT2_Mm to SINE_B1/Alu, ZFP352 can trigger spontaneous dissolution of the totipotency network. Our study highlights the importance of different retrotransposons sub-families in facilitating the timely and programmed cell fates transition during early embryogenesis.


Cerebral Imaging in Patients with COVID-19 and Neurological Symptoms: First Experience from two University Hospitals in Northern Germany.
To describe findings on cerebral imaging in patients with COVID-19 and neurological symptoms at two German university hospitals. Patients with COVID-19 and neurological symptoms and cerebral imaging (CT or MRI) were included. A chart review regarding neurological symptoms, COVID-19 and imaging findings was conducted. 12 patients (4 females, age 68 ± 12 years) could be included. Three patients had acute findings. Two patients had acute and subacute cerebral ischemia, one patient had additional intracranial hemorrhages and presumed central pontine myelinolysis. One patient had presumed COVID-19-associated pansinusitis. Findings on cerebral imaging in patients with COVID-19 are uncommon and nonspecific. However, cerebral ischemia is regularly encountered and patients should be evaluated for stroke symptoms. · Approx. 20 % of patients with COVID-19 develop neurological symptoms.. · Findings on cerebral imaging in patients with COVID-19 are heterogeneous and nonspecific.. · The most common findings are cerebral ischemia and hemorrhages.. · Jensen-Kondering U, Neumann A, Margraf N et al. Cerebral Imaging in Patients with COVID-19 and Neurological Symptoms: First Experience from two University Hospitals in Northern Germany. Fortschr Röntgenstr 2021; 193: 667 - 671.


Computer analysis of etiology and pregnancy rate in 636 cases of primary infertility.
Since the rate of pregnancy is a function of time, conventional pregnancy rates (number of patients achieving pregnancy per number of patients treated) are inadequate for counseling unless the follow-up period is specified. To overcome this problem, the expectancy of pregnancy for 636 cases of primary infertility was calculated with the assumption that the patients were followed up indefinitely. The overall "conventional" pregnancy rate was 38%, whereas the overall expectancy of pregnancy was 64%. Endometriosis was found to be the most common factor, comprising 25% of the cases, with a pregnancy rate of 31% and an expectancy of 52%. The expectancy of future pregnancy in a patient who has not achieved pregnancy by a given time is presented for each etiologic factor. This paper also presents a comparison of expectancies of pregnancy by different treatments, which may be helpful in selecting appropriate therapy.


[Current methods of systemic amyloidosis diagnosis and monitoring of its course].
To determine clinical significance of measuring blood levels of protein precursors of AA- and AL-amyloidosis - SAA and immunoglobulin free light chains (ILC), respectively. SAA concentrations were studied with ELISA in 43 rheumatoid arthritis (RA) patients including complicated with reactive AA-amyloidosis (n = 31). Inflammation activity and its severity were studied (indices Li, richi, HAQ, DAS4). A modern quantitative nephelometric method Freelite estimated ILC levels in 31 patients with AL-amyloidosis. Patients with RA complicated with AA-amyloidosis and free of it had a strong correlation between blood serum SAA concentration and activity of joint disease. Elevated SAA concentrations to 160 mg/l (normal 10 mg/l) were detected in many patients with clinical remission of the joint syndrome. Significal inhibition of AA-amyloidosis progression was seen only in SAA concentration drop under 60 mg/l. For AL-amyloidosis patients ILC fall by less than 3 normal value means a 6-time increase in chances of a favourable outcome. Monitoring of blood levels of proteins precursors of AA- and AL-amyloidosis is a key factor in prognosis of the disease and treatment efficacy.


[Statistical use of a database (Bull-SOPRA-ADICAP system). Application in the study of cancers in women].
The author analyses the frequency of cancer among women for 2 years at pathological department of Bichat's hospital. He presents a method about how to use the computer système Bull-SOPRA of "Assistance Publique de Paris". Among 13,778 women, he counts 750 primary invasive malignant tumors which 3/4 are grouped among fifties to eighties. The author notes cancers frequency doubles nearly every 10 years and notes an often late appearance of breast cancers which are known to reach women between 60 to 90.


Applying MAP-MRI to Identify the WHO Grade and Main Genetic Features of Adult-type Diffuse Gliomas: A Comparison of Three Diffusion-weighted MRI Models.
Currently, there is no noninvasive method to effectively judge the genotype of diffuse gliomas. We explored the association between mean apparent propagator-MRI (MAP-MRI) and WHO grade 2/3, IDH 1/2 mutations, and chromosome 1p/19q combined deletion genotypes in adult-type diffuse gliomas and compared it with the diagnostic efficiency of diffusion tensor imaging (DTI) and diffusional kurtosis imaging (DKI). We prospectively recruited 67 participantshistopathologically diagnosed with adult-type diffuse gliomas. Routine MRI, DKI, and DSI were performed before surgery. The extreme and average partial diffusion indexes of solid tumors were measured. A comprehensive assessment of statistically significant diffusion parameters was performed after Bonferroni correction, including ROC curves, correct classification percentage (CCP), integrated discrimination improvement (IDI), net reclassification improvement (NRI), and k-fold cross validation. For differentiating WHO grade 2/3, q-space inverse variance (QIV), mean kurtosis (MK), non-Gaussianity (NG), and return to the origin probability (RTOP) were different (p' < .05), with the mean QIV exhibiting the best diagnostic efficacy and stability (AUC = 0.973, CCP = 0.906). We observed significant differences in mean diffusivity (MD), mean square displacement, QIV, MK, and RTOP between the IDH wild-type and IDH mutant groups (p' < .001) (AUC, 0.806-0.978) and MAP-MRI showed a higher IDI than DTI and DKI (0.094-0.435, NRI > 0, respectively). For the chromosome 1p/19q combined deletion, the minimum QIV was different between the overall (p' < .05) and no significant differences in MD and MK was observed. MAP-MRI effectively predicts the WHO grade 2/3, IDH 1/2 mutations, and chromosome 1p/19q combined deletion in adult-type diffuse gliomas, and it may perform better than DTI and DKT.


Bta-miR-200b promotes endometrial epithelial cell apoptosis by targeting MYB in cattle.
Embryonic mortality is considered to be one of the main reasons for reduced conception rates in the cattle industry. Insufficient endometrial receptivity is a major factor resulting in embryo implantation failure and losses. Apoptosis of endometrial epithelial cells is an important process during establishment of uterine receptivity and embryo implantation. The aim of this study was to explore the role of bta-miR-200b on endometrial epithelial cell apoptosis in cattle. Overexpression of bta-miR-200b upregulated the expression of proapoptotic gene BCL2 associated X, apoptosis regulator (BAX) and endometrial receptivity marker gene osteopontin (OPN) at mRNA and protein level in bovine endometrial epithelial cells. Moreover, overexpression of bta-miR-200b was able to inhibit proliferation and promote apoptosis of bovine endometrial epithelial cells by arresting the cell cycle at the G0/G1 phase. MYB Proto-Oncogene (MYB) was verified to be a target of bta-miR-200b in bovine endometrial epithelial cells using dual-luciferase reporter assay. Transfection of bta-miR-200b mimics decreased the mRNA and protein expression of MYB. Overexpression of MYB decreased the effect of bta-miR-200b on apoptosis of bovine endometrial epithelial cells. Our findings suggest that bta-miR-200b can affect the apoptosis of endometrial epithelial cells in cattle by targeting the MYB gene.


A rapid method for the inactivation of virus infectivity prior to assay for interferons.
Virus infectivity in samples of culture medium or suspensions of animal tissue which are required for interferon assay can be rapidly and conveniently inactivated by overnight incubation with beta-propiolactone (BPL). As BPL hydrolyses spontaneously samples can be assayed with no further treatment. BPL does not affect the interfering activity of alpha, beta or gamma mouse interferons.


Tunica Vaginalis Graft Use for Repair of Traumatic Testicular Rupture: A Case Report.
Testicular rupture is a rare but serious condition which requires immediate and emergent surgical intervention in order to preserve fertility and maintain gonadal hormone function. We present here a case of a 16-year-old male who suffered a shattered right testicle following gunshot wound. Additionally, the left cord structures were also hit with possible compromise of the left testicle. He underwent scrotal exploration with reconstruction of the right tunica albuginea with a tunica vaginalis graft. The right testicle was found to be viable within 2months postoperatively with normal arterial and venous flow seen on Doppler scrotal ultrasound. We propose that tunica vaginalis can be used successfully as a graft to manage testicular rupture.


[Gardner-Diamond syndrome in a young man: A case report and literature review].
Gardner-Diamond syndrome is a rare condition secondary to a sensitization to self-erythrocytes. It is predominantly seen in women and presents as a painful ecchymotic disorder. An underlying psychiatric disease or a triggering psychological stress is of important diagnostic value. We report a 24-year-old patient who presented with intermittent spontaneous painful ecchymosis since 5 years. Complementary investigations failed to identify an organic disorder. Gardner-Diamond syndrome was retained because of the clinical presentation, the negativity of diagnostic work-up and the identification of a psychological trauma. Patient management (pain, psychological support) is difficult, justifying a multidisciplinary approach. Gardner-Diamond syndrome is a rare and unrecognized disorder, which should be discussed in the presence of ecchymotic or purpuric lesions that do not have a diagnostic orientation. Early recognition of this disorder enables initiation of an appropriate management, but also limits unnecessary additional explorations.


Preschool blood lead levels, language competency, and substance use in adolescence.
Elevated lead levels in children are a persistent public health problem, particularly in urban areas in the United States, yet few prospective studies have examined the association of childhood lead levels with substance use in adolescence. To determine the association of early lead levels with adolescent substance use and whether childhood IQ, language skills, and externalizing (aggressive and disruptive) behavior mediate the association, controlling for confounding biological and environmental factors. The participants (N = 265) were a subsample of a prospective birth cohort study on the developmental effects of prenatal cocaine exposure in the Midwest United States. Blood lead levels (BLL) were assessed at age 4, IQ at age 11, language skills and externalizing behavior at age 12, and substance (alcohol, tobacco, marijuana) use and substance use-related problems at age 15. Biologic assays (hair, urine, bloodspots), along with self-report, were utilized to determine adolescent substance use. Path analyses were conducted to examine the direct and indirect associations of BLL with adolescent substance use. The children's mean BLL at 4 years of age was 7.07 (SD = 4.12) μg/dL. Approximately 31% of adolescents used tobacco or marijuana, 40% used alcohol, and 23% reported experiencing substance use-related problems at age 15.7 (SD = 0.28). Elevated BLL was related to a higher likelihood of substance use. Childhood language skills fully mediated the relationship of BLL with substance use-related problems. IQ was related to neither substance use nor substance use-related problems. Elevated BLL in preschool years is a risk factor for adolescent substance use and related problems. Early screening and intervention for language impairment may reduce substance use-related problems.


Automated analysis of heterogeneous carbon nanostructures by high-resolution electron microscopy and on-line image processing.
High-resolution electron microscopy is an efficient tool for characterizing heterogeneous nanostructures; however, currently the analysis is a laborious and time-consuming manual process. In order to be able to accurately and robustly quantify heterostructures, one must obtain a statistically high number of micrographs showing images of the appropriate sub-structures. The second step of analysis is usually the application of digital image processing techniques in order to extract meaningful structural descriptors from the acquired images. In this paper it will be shown that by applying on-line image processing and basic machine vision algorithms, it is possible to fully automate the image acquisition step; therefore, the number of acquired images in a given time can be increased drastically without the need for additional human labor. The proposed automation technique works by computing fields of structural descriptors in situ and thus outputs sets of the desired structural descriptors in real-time. The merits of the method are demonstrated by using combustion-generated black carbon samples.


Surgical management of pediatric Graves' disease: an effective definitive treatment.
The optimal treatment for pediatric Graves' disease (GD) is controversial. Antithyroid drugs are often used initially, but they are associated with a high failure rate. Therefore alternative therapies have become important. In the present study, we analyze our institution's experience regarding the safety and efficacy of thyroid surgery among pediatric patients with GD. This is a retrospective chart review of 27 pediatric patients (age ≤ 18 years) with GD who underwent thyroid surgery between 1991 and 2009 at a single academic Institution. We recorded preoperative, intraoperative, and short-term postoperative data. All 27 patients were initially treated with thionamides. The high rate of hyperthyroidism relapse after discontinuation of medical treatment, age < 5 years, adverse reaction to medical therapy, severe ophthalmopathy, and patient preference justified the final decision to proceed with surgery as definitive therapy. All patients underwent total thyroidectomy. We had no mortality; surgical complications were rare: 4 (14.8 %) cases of transient hypocalcemia, 1 (3.7 %) of permanent hypocalcemia, 3 (11.1 %) of transient RLN neuropraxia, and 2 (7 %) of keloid scar. No bleeding, permanent RLN palsy or relapse hyperthyroidism were reported. Surgical therapy for pediatric GD performed by experienced thyroid surgeons is a safe, definitive and cost-effective treatment.


Patulin suppresses α1-adrenergic receptor expression in HEK293 cells.
Patulin (PAT) is a common mycotoxin contaminant of apple products linked to impaired metabolic and kidney function. Adenosine monophosphate activated protein kinase (AMPK), abundantly expressed in the kidney, intercedes metabolic changes and renal injury. The alpha-1-adrenergic receptors (α1-AR) facilitate Epinephrine (Epi)-mediated AMPK activation, linking metabolism and kidney function. Preliminary molecular docking experiments examined potential interactions and AMPK-gamma subunit 3 (PRKAG3). The effect of PAT exposure (0.2-2.5 µM; 24 h) on the AMPK pathway and α1-AR was then investigated in HEK293 human kidney cells. AMPK agonist Epi determined direct effects on the α1-AR, metformin was used as an activator for AMPK, while buthionine sulphoximine (BSO) and N-acetyl cysteine (NAC) assessed GSH inhibition and supplementation respectively. ADRA1A and ADRA1D expression was determined by qPCR. α1-AR, ERK1/2/MAPK and PI3K/Akt protein expression was assessed using western blotting. PAT (1 µM) decreased α1-AR protein and mRNA and altered downstream signalling. This was consistent in cells stimulated with Epi and metformin. BSO potentiated the observed effect on α1-AR while NAC ameliorated these effects. Molecular docking studies performed on Human ADRA1A and PRKAG3 indicated direct interactions with PAT. This study is the first to show PAT modulates the AMPK pathway and α1-AR, supporting a mechanism of kidney injury.


Duplicate bladder exstrophy: a unique variant.
Duplicate bladder exstrophy is an extremely rare congenital malformation. Two forms have been described, the anteroposterior form and the collateral form, which is the less common. We report a case of bladder exstrophy in association with a duplicated lower urinary tract, omphalocele, colic duplication and diphallia. Fewer than 30 cases of duplicate bladder exstrophy have been described previously, emphasizing the embryologic significance of this case. To our knowledge it is the first reported case of such an association of anomalies with the exstrophy-epispadias complex.


AfterQC: automatic filtering, trimming, error removing and quality control for fastq data.
Some applications, especially those clinical applications requiring high accuracy of sequencing data, usually have to face the troubles caused by unavoidable sequencing errors. Several tools have been proposed to profile the sequencing quality, but few of them can quantify or correct the sequencing errors. This unmet requirement motivated us to develop AfterQC, a tool with functions to profile sequencing errors and correct most of them, plus highly automated quality control and data filtering features. Different from most tools, AfterQC analyses the overlapping of paired sequences for pair-end sequencing data. Based on overlapping analysis, AfterQC can detect and cut adapters, and furthermore it gives a novel function to correct wrong bases in the overlapping regions. Another new feature is to detect and visualise sequencing bubbles, which can be commonly found on the flowcell lanes and may raise sequencing errors. Besides normal per cycle quality and base content plotting, AfterQC also provides features like polyX (a long sub-sequence of a same base X) filtering, automatic trimming and K-MER based strand bias profiling. For each single or pair of FastQ files, AfterQC filters out bad reads, detects and eliminates sequencer's bubble effects, trims reads at front and tail, detects the sequencing errors and corrects part of them, and finally outputs clean data and generates HTML reports with interactive figures. AfterQC can run in batch mode with multiprocess support, it can run with a single FastQ file, a single pair of FastQ files (for pair-end sequencing), or a folder for all included FastQ files to be processed automatically. Based on overlapping analysis, AfterQC can estimate the sequencing error rate and profile the error transform distribution. The results of our error profiling tests show that the error distribution is highly platform dependent. Much more than just another new quality control (QC) tool, AfterQC is able to perform quality control, data filtering, error profiling and base correction automatically. Experimental results show that AfterQC can help to eliminate the sequencing errors for pair-end sequencing data to provide much cleaner outputs, and consequently help to reduce the false-positive variants, especially for the low-frequency somatic mutations. While providing rich configurable options, AfterQC can detect and set all the options automatically and require no argument in most cases.