Simple Method to Produce in vitro Pyrenophora tritici-repentis Teleomorph.
A fungus Pyrenophora tritici-repentis induces tan spot of wheat which is a foliar disease that causes yield loss to wheat crops worldwide. In this study, a new, simple and non-costly technique was performed to produce the sexual stage of this fungus in culture, within 9 weeks using wheat straw. This protocol will be helpful to researchers studying the biology of sexual stage development, disease epidemiology and genetics of this fungus.


Immunoglobulin heavy chain/light chain pair measurement is associated with survival in diffuse large B-cell lymphoma.
Elevated serum free light chains (FLCs) have been associated with an unfavorable prognosis in diffuse large B-cell lymphoma (DLBCL). The aim of this study was to determine the clinical relevance of a quantitative assessment of intact circulating immunoglobulin (Ig), using serum Ig heavy chain/light chain pair (HLC) measurements in patients with DLBCL. FLC and HLC were measured in 409 serum samples of patients with DLBCL included in the LNH03-B clinical trial program of the Groupe d'Etudes des Lymphomes de l'Adulte (GELA). Patients with an abnormal IgMκ/IgMλ ratio or an abnormal FLC ratio more frequently displayed adverse clinical characteristics. Patients with abnormal IgMκ/IgMλ ratios had inferior progression-free survival (PFS) and overall survival (OS) as compared to patients with a normal ratio in the overall cohort (5-year PFS 44.9% vs. 69.3%, p = 0.0003 and 5-year OS 50.8% vs. 78.1%, p = 0.0003) and in the R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) cohort (5-year OS 43.5% vs. 70.3%, p = 0.003). In multivariate analysis, including elevated FLC/HLC and International Prognostic Index (IPI), an abnormal IgMκ/IgMλ ratio (hazard ratio [HR] = 1.54, 95% confidence interval [CI] 1.03-2.3, p = 0.03) remained predictive of shorter progression-free survival. Gene expression profile experiments and immunohistochemistry indicate that this measurement is at least partially related to tumor cell secretion. Both elevated serum FLCs and an abnormal IgMκ/IgMλ ratio are associated with unfavorable outcomes in patients with DLBCL treated by R-CHOP.


Interventions to promote adherence to antiretroviral therapy in Africa: a network meta-analysis.
Adherence to antiretroviral therapy (ART) is necessary for the improvement of the health of patients and for public health. We sought to determine the comparative effectiveness of different interventions for improving ART adherence in HIV-infected people living in Africa. We searched for randomised trials of interventions to promote antiretroviral adherence within adults in Africa. We searched AMED, CINAHL, Embase, Medline (via PubMed), and ClinicalTrials.gov from inception to Oct 31, 2014, with the terms "HIV", "ART", "adherence", and "Africa". We created a network of the interventions by pooling the published and individual patients' data for comparable treatments and comparing them across the individual interventions with Bayesian network meta-analyses. The primary outcome was adherence defined as the proportion of patients meeting trial defined criteria; the secondary endpoint was viral suppression. We obtained data for 14 randomised controlled trials, with 7110 patients. Interventions included daily and weekly short message service (SMS; text message) messaging, calendars, peer supporters, alarms, counselling, and basic and enhanced standard of care (SOC). Compared with SOC, we found distinguishable improvement in self-reported adherence with enhanced SOC (odds ratio [OR] 1·46, 95% credibility interval [CrI] 1·06-1·98), weekly SMS messages (1·65, 1·25-2·18), counselling and SMS combined (2·07, 1·22-3·53), and treatment supporters (1·83, 1·36-2·45). We found no compelling evidence for the remaining interventions. Results were similar when using viral suppression as an outcome, although the network contained less evidence than that for adherence. Treatment supporters with enhanced SOC (1·46, 1·09-1·97) and weekly SMS messages (1·55, 1·01-2·38) were significantly better than basic SOC. Several recommendations for improving adherence are unsupported by the available evidence. These findings can inform future intervention choices for improving ART adherence in low-income settings. None.


Prediction of Bloodstream Infection Due to Vancomycin-Resistant Enterococcus in Patients Undergoing Leukemia Induction or Hematopoietic Stem-Cell Transplantation.
Bloodstream infection (BSI) to due vancomycin-resistant Enterococcus (VRE) is an important complication of hematologic malignancy. Determining when to use empiric anti-VRE antibiotic therapy in this population remains a clinical challenge. A single-center cohort representing 664 admissions for induction or hematopoietic stem-cell transplant (HSCT) from 2006 to 2014 was selected. We derived a prediction score using risk factors for VRE BSI and evaluated the model's predictive performance by calculating it for each of 16232 BSI at-risk inpatient days. VRE BSI incidence was 6.5% of admissions (2.7 VRE BSI per 1000 BSI at-risk days). Adjusted 1-year mortality and length of stay were significantly higher in patients with VRE BSI. VRE colonization (adjusted odds ratio [aOR] = 8.4; 95% confidence interval [CI] = 3.4-20.6; P < .0001), renal insufficiency (aOR = 2.4; 95% CI = 1.0-5.8; P = .046), aminoglycoside use (aOR = 4.7; 95% CI = 2.2-9.8; P < .0001), and antianaerobic antibiotic use (aOR = 2.8; 95% CI = 1.3-5.8; P = .007) correlated most closely with VRE BSI. A prediction model with optimal performance included these factors plus gastrointestinal disturbance, severe neutropenia, and prior beta-lactam antibiotic use. The score effectively risk-stratified patients (area under the receiver operating curve = 0.84; 95% CI = 0.79-0.89). At a threshold of ≥5 points, per day probability of VRE BSI was increased nearly 4-fold. This novel predictive score is based on risk factors reflecting a plausible pathophysiological model for VRE BSI in patients with hematological malignancy. Integrating VRE colonization status with risk factors for developing BSI is a promising method of guiding rational use of empiric anti-VRE antimicrobial therapy in patients with hematological malignancy. Validation of this novel predictive score is needed to confirm clinical utility.


Variation in Definitions of Immobility in Pharmacological Thromboprophylaxis Clinical Trials in Medical Inpatients: A Systematic Review.
Although immobility is a common risk factor for venous thromboembolism (VTE) in medical inpatients, lack of a consistent definition of this term may limit accurate assessment of VTE risk for thromboprophylaxis. To examine various definitions of immobility used in recent pharmacological thromboprophylaxis clinical trials. PubMed and relevant references from articles/reviews from 2008 to 2016 were searched. Randomized controlled trials (RCTs) and other clinical studies involving adult hospitalized medical patients in acute care hospital settings that used the term immobility were selected. Two investigators independently abstracted data in duplicate, and accuracy was checked by a third investigator. Twenty-one clinical studies were included. There was heterogeneity among individual VTE risk factors, with respect to the definition of immobility in medical inpatients in these trials. Thirteen studies utilized objective criteria to define "immobility" including duration (12 studies) and distance or time walked (6 studies). In contrast, 7 studies focused principally on subjective definitions (ie, describing the nature of immobility rather than specifying its quantitative measurement). Three RCTs vaguely defined the level of patient's immobility after hospitalization. Despite the well-known effectiveness of pharmacological thromboprophylaxis for the prevention of VTE in acutely ill medical patients, there is no current consensus on how to define immobility. The heterogeneous nature of definitions of immobility has led to uncertainty about the importance of immobility in VTE risk assessment models. Although clinical studies have incorporated varying definitions of immobility into their inclusion criteria, immobility as a specific VTE risk factor has not been clearly defined.


CD40 ligation mediates plaque-associated tau phosphorylation in beta-amyloid overproducing mice.
Neuritic dystrophy with amyloid burden and neurofibrillary tangles are pathological hallmarks of Alzheimer's disease. Genetic disruption of CD40 or CD40L alleviates amyloid burden, astrocytosis, and microgliosis in transgenic animal models of Alzheimer's disease. It has been reported that phosphorylated tau-positive dystrophic neurites are observed in transgenic mice over-expressing human mutant beta-amyloid precursor protein (Tg2576). Here, we studied the pattern of phosphorylated tau (labeled with AT8, CP13, PG5, and PHF1 antibodies) and plaques using immunohistochemical techniques. Phosphorylated tau-positive dystrophic neurites were exclusively associated with Congo red-positive plaques as previously reported. Further, we show that CD40L or CD40 deficiency reduces the mean ratio of dystrophic neurite area to congophilic plaque area and the level of expression of cdk5 and p35/p25 in mice. In addition, we show that in a human neuroblastoma cell line treated with CD40L, cdk5 and p35/p25 are increased. Together, our data suggest that CD40-CD40L interaction has an effect on tau phosphorylation independent of beta-amyloid pathology, and that this effect may occur through a decrease of cdk5 and p35/p25.


Incidence and severity of retinopathy of prematurity in extremely premature infants.
To analyze incidence and severity of retinopathy of prematurity (ROP) among extremely premature infants. Retrospective, longitudinal study. We studied the data concerning 207 infants whose gestational ages (GAs) were equal to 27 weeks or fewer and who were admitted to a neonatal intensive care unit between July 2006 and July 2010. Data were extracted from the Canadian Neonatal Network, which maintains clinical information about neonates, and were confirmed by reviewing medical charts. Infants were classified into 2 groups: the GAs of the infants in group 1 were ≤ 25 weeks; those in group 2 had GAs between 26 and 27 weeks. The incidence and severity of ROP were assessed in the total screened population and between groups. The overall incidence of any ROP was 64.7%; 88% of infants in group 1 had any ROP compared to 48% infants in group 2. The overall incidence of type 1 ROP was 11.6%; in group 1 it was 24.4%, compared to 2.5% in group 2. Type 1 ROP was significantly associated with birth weight in grams (p < 0.001; OR = 8.20) and GA (p < 0.001; OR = 2.46). There was no difference in mean postmenstrual age at first ROP onset between group 1 and group 2 (33.5 vs 33.9 weeks, respectively). PMA at time of ROP diagnosis was not associated with development of type 1 ROP (p = 0.75; OR = 0.94; CI 0.62-1.41). Extremely premature infants with lower GA had a higher incidence of type 1 ROP. Earlier presentation of ROP did not predict development of type 1 ROP. No infant with a GA > 26 weeks at birth or birth weight > 1000 g had type 1 ROP.


Recommended nutrient intake for dietary fibre: bar set too high for malaysians?
This article presents findings from three separate data sets on food consumption in apparently healthy Malaysian adult males and females aged 22-60 years, and secondary data extracted from the Malaysian Adult Nutrition Survey (MANS) 2003. Assessment of food intake by 24-hour recall or the food diary method and use of the nutrient calculator- DietPLUS- to quantify intake of macronutrients and dietary fibre (DF) in the primary data, revealed low mean DF intakes of 10.7±1.0 g/day (Course participants, n=52), 15.6 ±1.2 (University sample, n=103), and 16.1±6.1 (Research Institute staff, n=25). An alarmingly high proportion of subjects (75 to 95%) in these three data sets did not meet the national population intake goal of 20-30 g DF/day. A list of 39 food items which contain fibre, extracted from the MANS 2003 report as being average amounts consumed daily by each Malaysian adult, provided 19.2 g DF which meant that >50% of Malaysian adults consumed less than the recommended DF intake of 20-30 g/day. This large deficit of actual intake versus recommended intakes is not new and is also observed in developed western nations. What is of great concern is that the preliminary findings presented in this article indicate that the national population goal of 20-30 g DF/day may be beyond the habitual diets of the majority of Malaysians. Appropriately, the authors propose the inclusion of a daily minimum requirement for DF intake in the Malaysian Dietary Guidelines, which would somewhat mimic the Malaysian Dietary Guidelines 1999 for dietary fat, as well as the stand taken by the Scientific Advisory Committee on Nutrition (SACN) of the United Kingdom. This minimum requirement, if agreed to, should not be higher than the 16 g DF or so provided by the hypothetical 'high-fibre' healthy diet exemplified in this article.


Hsp72 release: mechanisms and methodologies.
To date there are two mechanisms that are recognized by which heat shock proteins (HSP) are released from cells; a passive release mechanism, including necrotic cell death, severe blunt trauma, surgery and following infection with lytic viruses, and an active release mechanism which involves the non classical protein release pathway in which HSPs are released within highly immunologically potent exosomes and as free HSP. This chapter describes the experimental procedures that have been developed to study the mechanism by which stress induces the release of HSP72 into the circulation and addresses the biological significance of circulating HSP72 to host defense against disease.


Total synthesis of (-)-saliniketals A and B.
A stereocontrolled total synthesis of the orthinine decarboxylase inhibitors saliniketals A and B is described. Key features of the 17-step route include the use of two boron aldol/reduction sequences to control six of the nine stereocenters, an intramolecular Wacker-type cyclization to install the bicyclic acetal core, and a late-stage Stille coupling to append the requisite (2 Z,4 E)-dienamide.


Azathioprine versus betamethasone for the treatment of parthenium dermatitis: a randomized controlled study.
Parthenium hysterophorus is the commonest cause of airborne contact dermatitis in India. Azathioprine has been shown to be effective and safe in parthenium dermatitis, but there are no reports of comparison of steroids and azathioprine in this condition. To study the therapeutic efficacy of azathioprine versus betamethasone in patients having contact dermatitis to parthenium and compare the side effects of the drugs. Fifty-five patients of airborne contact dermatitis to parthenium were randomly assigned to treatment with azathioprine 100 mg daily (group A) or betamethasone 2 mg daily (group B), for 6 months in a blinded manner. The patients were evaluated every month for 6 months to determine the response to treatment and side effects and then further followed up for another 6 months to determine any relapse. There were 26 patients in group A and 29 in group B, of which 20 patients of group A and 21 of group B completed the study. Nineteen (95%) patients in group A and all 21 (100%) patients in group B had an excellent response (complete remission) to treatment (P=0.0156 vs. 0.0005). The patients in group B, however, had more adverse effects (Fisher exact, P<or=0.05). Nine (45%) patients in group A and 14 (67%) patients in group B relapsed during the post-treatment follow-up. Azathioprine and betamethasone appear to be almost equally effective (P=0.0156 vs. 0.0005) in the treatment of parthenium dermatitis. However, adverse effects and relapses were observed to be more frequent in patients treated with betamethasone.


New benzylureas as a novel series of potent, nonpeptidic vasopressin V2 receptor agonists.
Vasopressin (AVP) is a hormone that stimulates an increase in water permeability through activation of V2 receptors in the kidney. The analogue of AVP, desmopressin, has proven an effective drug for diseases where a reduction of urine output is desired. However, its peptidic nature limits its bioavailability. We report herein the discovery of potent, nonpeptidic, benzylurea derived agonists of the vasopressin V2 receptor. We describe substitutions on the benzyl group to give improvements in potency and subsequent modifications to the urea end group to provide improvements in solubility and increased oral efficacy in a rat model of diuresis. The lead compound 20e (VA106483) is reported for the first time and has been selected for clinical development.


AA amyloid nephropathy with predominant vascular deposition in Crohn's disease.
A 44-year-old man with a 17-year history of Crohn's disease (CD) was referred to our nephrology department on suspicion of drug-induced nephrotoxicity. Over the preceding 18 months, he had slowly progressive renal insufficiency with slight urinary abnormalities. His disease activity had been well controlled up to that point with 5-aminosalicylic acid and azathiopurine. Laboratory examination revealed slight proteinuria without hematuria and an elevated serum creatinine level of 1.4 mg/dl. Pathological examination revealed amyloid A (AA) deposition in the kidney, predominantly in the arterial and arteriolar walls with little to none in the glomerular capillaries. AA amyloidosis is typically accompanied by glomerular amyloid deposition and massive proteinuria. In the present case, however, vascular amyloid deposition was predominant, and the renal function was deteriorated with slight urinary abnormalities. The present case confirmed the importance of conducting a definitive pathological diagnosis of renal insufficiency in CD patients.


Standards for the optimal management of COPD: a summary.
Tobacco smoking is the main cause of COPD, and encouragement and support in smoking cessation is the best way to help the patient with COPD. The three major goals of COPD management are to lessen airflow limitation, to prevent and treat secondary medical complications, and to decrease respiratory symptoms and improve quality of life. Outpatient pharmacotherapy should be organized in a stepwise manner according the severity of disease, the aims being to induce bronchodilation, reduce inflammation, and facilitate expectoration, although the role of anti-inflammatory and mucolytic treatment of COPD has not been clearly established. Patients whose conditions are not well controlled with optimal pharmacotherapy are candidates for enrollment in a pulmonary rehabilitation program. Correction or prevention of hypoxemia is a priority, and long-term oxygen therapy supplementation prolongs survival in hypoxemic patients. With only limited data on criteria for hospital admission and the objectives of hospitalization, the published standards on the management of COPD include an expert consensus statement on these aspects of hospital care. Surgery, special considerations such as sleep, nutrition, and air travel, and ethical issues are discussed.


Coupling ontology driven semantic representation with multilingual natural language generation for tuning international terminologies.
The importance of clinical communication between providers, consumers and others, as well as the requisite for computer interoperability, strengthens the need for sharing common accepted terminologies. Under the directives of the World Health Organization (WHO), an approach is currently being conducted in Australia to adopt a standardized terminology for medical procedures that is intended to become an international reference. In order to achieve such a standard, a collaborative approach is adopted, in line with the successful experiment conducted for the development of the new French coding system CCAM. Different coding centres are involved in setting up a semantic representation of each term using a formal ontological structure expressed through a logic-based representation language. From this language-independent representation, multilingual natural language generation (NLG) is performed to produce noun phrases in various languages that are further compared for consistency with the original terms. Outcomes are presented for the assessment of the International Classification of Health Interventions (ICHI) and its translation into Portuguese. The initial results clearly emphasize the feasibility and cost-effectiveness of the proposed method for handling both a different classification and an additional language. NLG tools, based on ontology driven semantic representation, facilitate the discovery of ambiguous and inconsistent terms, and, as such, should be promoted for establishing coherent international terminologies.


Treatment of chronic mallet fractures using extension-block Kirschner wire.
Eleven patients with chronic mallet fractures that were seen later than four weeks after injury were treated by extension-block Kirschner wire technique. The average duration from injury to operative treatment was 56 days (range, 28-111). The follow-up evaluations took place after a mean of eight months. The radiographic bone union was obtained in all patients. The average extension loss of the DIP joint was 4 degree (range, 0-15) and the average flexion was 68 degree (range, 43-90). The results according to Crawford's criteria were six excellent, two good, two fair, and one poor. We would say that the technique we treated is effective method of treatment for younger patients with chronic mallet fractures.


Peak offset times as an indication of stress relaxation during tableting on a rotary tablet press.
During powder compaction on a Manesty Betapress, peak pressures, Pmax, are reached before the punches are vertically aligned with the centres of the upper and lower compression roll support pins. The interval between the time taken to reach this alignment and the time to reach Pmax is defined as the peak offset time, t(off). The duration of t(off) depends on the ability of the compacted powder to relieve stress and is an indication of the predominant mechanisms of particle deformation during consolidation. Thus, at a given Pmax, short t(off) values are characteristic of materials that consolidate mainly by brittle fracture while longer values indicate an increase in plastic flow. On the Betapress, the decrease in stress during t(off) occurs under conditions approaching constant strain and t(off) therefore, is an indirect measure of stress relaxation. Stress relaxation, and hence t(off), decreases with increase in Pmax due to the reduction in the porosity of the compact and consequent restriction of plastic flow into the void spaces. In addition to Pmax, the effects of variables such as punch head geometry, press speed and formulation on t(off) are reported.


Domain architecture and oligomerization properties of the paramyxovirus PIV 5 hemagglutinin-neuraminidase (HN) protein.
The mechanism by which the paramyxovirus hemagglutinin-neuraminidase (HN) protein couples receptor binding to activation of virus entry remains to be fully understood, but the HN stalk is thought to play an important role in the process. We have characterized ectodomain constructs of the parainfluenza virus 5 HN to understand better the underlying architecture and oligomerization properties that may influence HN functions. The PIV 5 neuraminidase (NA) domain is monomeric whereas the ectodomain forms a well-defined tetramer. The HN stalk also forms tetramers and higher order oligomers with high alpha-helical content. Together, the data indicate that the globular NA domains form weak intersubunit interactions at the end of the HN stalk tetramer, while stabilizing the stalk and overall oligomeric state of the ectodomain. Electron microscopy of the HN ectodomain reveals flexible arrangements of the NA and stalk domains, which may be important for understanding how these two HN domains impact virus entry.


Drug Delivery Applications of Core-Sheath Nanofibers Prepared by Coaxial Electrospinning: A Review.
Electrospinning has emerged as one of the potential techniques for producing nanofibers. The use of electrospun nanofibers in drug delivery has increased rapidly over recent years due to their valuable properties, which include a large surface area, high porosity, small pore size, superior mechanical properties, and ease of surface modification. A drug loaded nanofiber membrane can be prepared via electrospinning using a model drug and polymer solution; however, the release of the drug from the nanofiber membrane in a safe and controlled way is challenging as a result of the initial burst release. Employing a core-sheath design provides a promising solution for controlling the initial burst release. Numerous studies have reported on the preparation of core-sheath nanofibers by coaxial electrospinning for drug delivery applications. This paper summarizes the physical phenomena, the effects of various parameters in coaxial electrospinning, and the usefulness of core-sheath nanofibers in drug delivery. Furthermore, this report also highlights the future challenges involved in utilizing core-sheath nanofibers for drug delivery applications.


Amino acid substitutions in the nonstructural region 5A of hepatitis C virus genotypes 2a and 2b and its relation to viral load and response to interferon.
The interferon sensitivity-determining region (ISDR) in nonstructural region 5A (NS5A) of hepatitis C virus genotype 1b has been reported to correlate with response to interferon therapy and viral load. Recently the correlation between NS5A and response to interferon in genotype 2a was also reported. We examined the region of genotypes 2a and 2b corresponding to the ISDR of genotype lb to elucidate its correlation with response to interferon and viral load. The sequences of amino acid positions 2213-2248 in NS5A were determined in 39 patients with genotype 2a and 12 patients with genotype 2b. In the patients infected with genotype 2a, the number of amino acid substitutions in the ISDR-corresponding region compared with the consensus sequence of genotype 2a was significantly correlated with viral load (p = -0.541, p < 0.001) and with response to interferon therapy (p < 0.05); 83% of the patients with three or more substitutions obtained sustained responses, whereas only 44% of those with less than three substitutions obtained sustained responses. Multivariate analysis confirmed that the number of substitutions in the ISDR-corresponding region of genotype 2a was one of the independent predictors of response to interferon therapy (discriminant coefficient = 1.35, p < 0.001). Substitutions in the ISDR-corresponding region in NS5A of hepatitis C virus genotype 2a was confirmed to correlate to viral load and response to interferon therapy. In genotype 2b, further work must be considered because of the small number of patients studied.


[Effects of cysteamine on the plasma levels of SS and some metabolic hormones in adult geese].
To know the effect of cysteamine (CS) on the plasma levels of somatostatin (SS) and some metabolic hormones in adult geese. Fourteen adult crossbred geese (Chuan white x Tai lake) fitted with chronic wing vein cannulas were used in this study to evaluate the effect of CS on SS, TSH, T3 and T4 levels. The experiment was consisted of control and treated phase. The diet was added CS at dosage of 100 mg/kg bw on the first day of the treated phase. The blood samples were collected from the cannulas and analyzed by radioimmunoassay. The plasma SS concentration was (1.87 +/- 0.10) microg/L in control phase. Whereas SS concentrations on day 1, 3, 5, 7 of treated phase were decreased markedly (P < 0.05 or P < 0.01). Thereafter it was rose on the seventh day, however it was still lower than that of control. The thyroid stimulating hormone (TSH) content (2.45 +/- 0.31 mIU/L) was significantly decreased by 21.63% (P < 0.01) on day 1, and 18.37% (P > 0.05) on day 3 and day 5. Comparing with control phase (5.41 +/- 0.98 microg/L), T4 contents were elevated by 60.26% (P < 0.01), 43.25% (P < 0.01), 37.15% (P < 0.01) and 16. 82% (P < 0.01) respectively on day 1, 3, 5, 7. T3 level was (1.05 +/- 0.06) microg/L in control phase, whereas the levels was significantly increased by 36.19% (P < 0.01) on day 3. Also, the insulin concentration was higher than that of control (4.43 +/- 0.41 mU/ L) by 18.28% (P < 0.05) on the day 5. These results indicate that CS can decrease the plasma SS and TSH levels, whereas increase the levels of T4, T3 and insulin, therefore change metabolism, improve the nutrition transform and accelerate the growth in geese.


Two-dimensional supramolecular organization of copper octaethylporphyrin and cobalt phthalocyanine on Au(111): molecular assembly control at an electrochemical interface.
Mixed adlayers of 2,3,7,8,12,13,17,18-octaethyl-21H,23H-porphine copper(II) (CuOEP) and cobalt(II) phthalocyanine (CoPc) were prepared by immersing Au(111) substrate in a benzene solution containing CuOEP and CoPc molecules, and they were investigated in 0.1 M HClO(4) by cyclic voltammetry (CV) and in-situ scanning tunneling microscopy (STM). The composition of the mixed adlayer consisting of CuOEP and CoPc molecules was found to vary depending on the immersion time. CoPc molecules displaced CuOEP molecules during the modification process with increasing immersion time, and the CuOEP molecules were completely replaced with CoPc molecules in the mixed solution after a long modification time. The two-component adlayer consisting of CuOEP and CoPc, which has a structure with the constituent molecules arranged alternately, was found to form either a p(9 x 3(square root)7R - 40.9 degrees) or a p(9 x 3(square root)7R - 19.1 degrees) structure, each involving two molecules on the Au(111) surface. The surface mobility and the molecular reorganization of CuOEP and CoPc were accelerated by modulation of the electrode potential. Different surface structures were produced at different electrode potentials, and hence potential modulation should allow a precisely controllable phase separation to take place in aqueous HClO(4).


Heck Migratory Insertion Catalyzed by a Single Pt Atom Site.
Single-atom catalysts (SACs) have generated excitement for their potential to downsize metal particles to the atomic limit with engineerable local environments and improved catalytic reactivities and selectivities. However, successes have been limited to small-molecule transformations with little progress toward targeting complex-building reactions, such as metal-catalyzed cross-coupling. Using a supercritical carbon-dioxide-assisted protocol, we report a heterogeneous single-atom Pt-catalyzed Heck reaction, which provides the first C-C bond-forming migratory insertion on SACs. Our quantum mechanical computations establish the reaction mechanism to involve a novel C-rich coordination site (i.e., PtC4) that demonstrates an unexpected base effect. Notably, the base was found to transiently modulate the coordination environment to allow migratory insertion into an M-C species, a process with a high steric impediment with no previous example on SACs. The studies showcase how SACs can introduce coordination structures that have remained underexplored in catalyst design. These findings offer immense potential for transferring the vast and highly versatile reaction manifold of migratory-insertion-based bond-forming protocols to heterogeneous SACs.


Production and epitope analysis of monoclonal antibodies against a Rhizobium leguminosarum biovar trifolii strain.
Heat-treated cells of Rhizobium leguminosarum biovar trifolii strain 162X95 were used to produce monoclonal antibodies (MAbs). The fusion produced three cross-reactive MAbs and eight MAbs specific for the immunizing strain and a group of five other R. trifolii strains from the same geographic region where 162X95 was isolated (California). Seven MAbs were analyzed by competitive enzyme-linked immunosorbent assay to determine the number of different epitopes detectable on strain 162X95. The results indicated that six MAbs reacted with the same or overlapping epitopes, and the seventh MAb gave inconclusive results.


Risk profile of coronary heart disease among the staff members of Qassim University, Saudi Arabia.
To estimate the risk profile of coronary heart disease (CHD) among the staff members of Qassim University and assess their knowledge in a screening campaign in Qassim region, Saudi Arabia. A cross-sectional study was conducted among male and female staff at Qassim University campus. All employees of Qassim University were invited to participate in the study. Data were collected through a self-administered questionnaire. The study sample size was 233 staff and employees. The data were entered and analyzed using SPSS version 18. The data analysis focused on providing point estimates for the risk factors. The study found that 30% of participants have one or more risk factors for CHD, namely obesity 20.6%, diabetes 10.3%, hypertension 12.4%, dyslipidemia 10.7%, and smokers (11.6%). About 54% of the participants have a family history of at least one chronic disease as a risk factor for CHD. The most common risk factor of CHD among the staff members is obesity by 20.6%. Risk factors for CHD are quite common among Qassim University staff. These findings need to increase the health education and disease promotion program as an important intervention to reduce the occurrence and severity of CHD risk factors and to improve the quality of the life of the staff members of Qassim University.


Mondani intraoral welding: historical process and main practical applications.
The intraoral welder was invented by Dr. Pierluigi Mondani during the early 70's to weld titanium needle implants to a titanium bar in patient's mouth and to load them immediately by means of resin prosthesis. The clinical use documented dates back to 1972. Over the years, many practical applications have been added to the initial one, which have expanded the use of this device. In this scientific work, main applications are described. The aim of the work was to trace the historical process of intra-oral welding according to Mondani and describe the main practical applications. Intra-oral welding is a process introduced by dr. Pier Luigi Mondani of Genova (Italy) which allows to firmly conjoin titanium implants of any shape by means of a titanium bar or also directly between them in the mouth during surgery. The immediate stabilization achieved by intraoral welding increases implants success rate, allows immediate loading even in situations of bone atrophy, saves implants that are running into failure, re-evaluates fractured implants, allows to stabilize submerged implants postponing prosthesis management, allows to achieve efficient rehabilitation protocols to deal with difficult cases. The 40-years' experience with intra-oral welding described in this article, confirms the ease of use and efficiency in providing immediate stabilization of titanium implants of all types.


Sequence Specificity in the Entropy-Driven Binding of a Small Molecule and a Disordered Peptide.
Approximately one-third of the human proteome is made up of proteins that are entirely disordered or that contain extended disordered regions. Although these disordered proteins are closely linked with many major diseases, their binding mechanisms with small molecules remain poorly understood, and a major concern is whether their specificity can be sufficient for drug development. Here, by studying the interaction of a small molecule and a disordered peptide from the oncogene protein c-Myc, we describe a "specific-diffuse" binding mechanism that exhibits sequence specificity despite being of entropic nature. By combining NMR spectroscopy, biophysical measurements, statistical inference, and molecular simulations, we provide a quantitative measure of such sequence specificity and compare it to the case of the interaction of urea, which is diffuse but not specific. To investigate whether this type of binding can generally modify intermolecular interactions, we show that it leads to an inhibition of the aggregation of the peptide. These results suggest that the binding mechanism that we report may create novel opportunities to discover drugs that target disordered proteins in their monomeric states in a specific manner.


John Hunter (1728-1793): founder of scientific surgery and precursor of oncology.
In the following article we briefly present the life and scientific work of John Hunter, founder of the experimental surgery, who by means of his researches and writings in the field of Oncology, contributed enormously to the development of this discipline. In reference to this matter, we quote some examples indicative of his work on Oncology.


The incidence and outcome of ischemic colitis in a population-based setting.
Population-based studies on patients with ischemic colitis (IC) are limited. We aimed to determine the incidence, risk factors and outcome of patients with IC. A retrospective nationwide study was conducted on adult patients with histologically confirmed IC in 2009-2013 in Iceland. IC patients were matched for age and gender with patients hospitalized with lower gastrointestinal bleeding. Data were collected on clinical presentation, comorbidities, smoking habits, management and outcome. Eighty-nine patients, 61 (69%) females and mean age of 65 years (±17), fulfilled the predetermined criteria. Females were older than males, 68 years (±14) vs. 59 years (±20) (p = .0170). The mean cumulative incidence was 7.3 cases per 100,000 inhabitants. A total of 57 (64%) patients presented with abdominal pain, hematochezia and diarrhea. IC was localized in the left colon in 78 (88%) patients. Overall, 62 (70%) patients had cardiovascular disease vs. 53 (60%) of control group (NS) and 55 (62%) had a history of smoking vs. 53 (60%) in control group (NS). Ten (11%) patients required surgery and/or died within 30-days from hospital admission. At the end of follow-up, 7 (9%) patients had experienced recurrence of IC with an estimated 3-year recurrence rate of 15%. IC is a common clinical phenomenon that affects a wide range of age groups, but is most prominent among elderly women. It typically presents with a clinical triad of abdominal pain, hematochezia and diarrhea. Most cases are mild and self-limiting with a good prognosis.


[Acid phosphatase activity during digestion in the anintestinal turbellaria Convoluta convoluta].
Studies have been made on changes in the activity of acid phosphatase during the digestion in the turbellaria C. convoluta. The increase of the enzymic activity of cytoplasm of the peripheral parenchyma at the initial stages after feeding (6 hours, 1 day) and gradual decrease of this activity at later stages (2,4 and 7 days) were noted. The presence of acid phosphatase in the nuclei and cytoplasm of cells of the central parenchyma at all stages of the digestive cycle is explained by degeneration of these cells which is associated with holocrine secretion of the digestive enzymes.


Noise-Robust Heart Rate Estimation Algorithm from Photoplethysmography Signal with Low Computational Complexity.
This paper introduces a noise-robust HR estimation algorithm using wrist-type PPG signals that consist of preprocessing block, motion artifact reduction block, and frequency tracking block. The proposed algorithm has not only robustness for motion noise but also low computational complexity. The proposed algorithm was tested on a data set of 12 subjects and recorded during treadmill exercise in order to verify and compare with other existing algorithms.


Relaxation dynamics of a polymer in a 2D confinement.
The molecular dynamics of oligomeric poly(propylene glycol) (PPG) liquids (MW=1000, 2000, and 4000 g/mol) confined in a two-dimensional layer-structured Na-vermiculite clay has been studied by broadband dielectric spectroscopy. The alpha-relaxation and the normal mode relaxation processes were studied for all samples in bulk and confinement. The most prominent experimental observation was that for the normal mode process: the relaxation rate in the clay is drastically shifted to lower frequencies compared to that of the bulk material. This slowing down is probably caused by the strongly reduced number of accessible chain conformations in two dimensions. Also the temperature dependence of the relaxation time for the normal mode process is strongly affected by the confinement. In contrast, for the alpha-relaxation of the confined polymers we observed only a slight increase of the relaxation rate at high temperatures compared to the corresponding bulk samples, and a decrease of its relaxation strength relative to the beta relaxation. Thus, the glass transition is unaffected by the 2D confinement, suggesting that the underlying phenomena responsible for the glass transition is the same as in bulk. Moreover, in the clay the intensity of the normal mode is stronger than that of the alpha-process, in contrast to the bulk samples where the opposite behavior is observed.


Proliferation of villous trophoblast of the human placenta in normal and abnormal pregnancies.
The proliferation of villous trophoblast in the human placenta was estimated throughout normal gestation and in term placentae from preeclamptic and smoking mothers by two different methods. These were: 1) labeling of DNA producing cells by bromodeoxyuridine (BrdU) followed by immunohistochemistry using a monoclonal anti-BrdU antibody, and 2) immunohistochemical identification of all proliferating cells by the monoclonal antibody Ki67. Both methods revealed comparable results. In uncomplicated pregnancies there was a remarkable decrease in the labeling indices from early gestation to term. This was the result of a diminution of the number of Langhans' cells, although the cell division rate within the Langhans' cell layer remained nearly constant throughout gestation. A prolongation of the cell cycle in the cytotrophoblast cells at term was indicated by an increase in the Ki67/BrdU ratio. Compared with normal term placentae, there was an increase in the trophoblast proliferation rate in preeclampsia, but not in placentae from smoking mothers. Moreover, the number of Langhans' cells was diminished in placentae from smokers. The results indicate that there are different pathogenetic mechanisms of placental impairment in preeclampsia and in maternal smoking. In preeclampsia an injury to the syncytiotrophoblast seems to lead to a repair hyperplasia of the cytotrophoblast, whereas in maternal smoking, there seems to be a direct toxic effect on the cytotrophoblastic cells.


[Bacterial colonization of the epithelial cells of gingival pockets].
Common methods for microbiologic examination of the gingival pocket contents in periodontitis are rarely used in practical periodontology. The author proposes to quantify epithelial cells contaminated by bacterial flora. Results of cytologic studies of smear impressions from 30 patients with periodontal diseases and from 13 normal subjects are presented, evidencing a significant elevation of bacterial contamination of the epithelium in the patients vs. that in normal subjects (66.51 +/- 3.5 vs. 44.66 +/- 4.75 percent).


Highly stable PtP alloy nanotube arrays as a catalyst for the oxygen reduction reaction in acidic medium.
Nanostructured Pt-metal alloys have shown impressive catalytic properties for the oxygen reduction reaction (ORR) in acidic medium, but their long-term stability has not been satisfactory. Herein, we look beyond the traditional Pt-metal alloys and have developed a new kind of Pt-nonmetal alloy electrocatalyst for the ORR. Specifically, the novel catalyst is composed of interconnected platinum monophosphide (PtP) alloy nanocrystals (∼3-4 nm) and featured supportless nanotube array morphologies. Due to the unique combination of composition and structure, the obtained PtP alloy nanotube arrays not only exhibited remarkable ORR activity, but also showed almost no degradation of the half-wave potential after accelerated durability tests. The result suggests that alloying Pt with a nonmetallic element (such as P) is indeed an effective approach to address the poor stability of Pt-based catalysts in acidic medium.


Twenty-four-hour serum levels of TSH in affective disorders.
As a part of a broad endocrine testing of patients with affective disorders the 24 h serum levels of thyrotropin (TSH) were investigated and correlated to the clinical history and disease symptoms. Thirty-two patients with the research diagnostic criteria of major depressive disorder were investigated. Twenty-six of these patients were reinvestigated in a state of full or partial clinical remission. Nine patients with unipolar and eight patients with bipolar affective disorders were also investigated in clinical remission. The control group comprised 32 healthy subjects. The results showed significantly lower 24 h serum levels of TSH and less variability of TSH levels during the 24 h period in the group with acute major depression compared with the controls. The 24 h serum levels of TSH normalized during clinical remission. Different subtypes of depression, different clusters of symptoms and severity of depression did not significantly correlate with the 24 h serum levels of TSH. There were also no significant correlations between abnormalities of the dexamethasone suppression test or nightly melatonin levels and the 24 h serum levels of TSH. The lower TSH levels seen in acute major depression could not be correlated to increased or decreased levels of peripheral thyroid hormones. The mechanism of the decreased 24 h serum levels of TSH is unclear. One possibility is an altered sensitivity in the thyrotrophs of the pituitary.


Cationic lanthanide complexes of neutral tripodal N,O ligands: enthalpy versus entropy-driven podate formation in water.
The cationic lanthanide complexes of two neutral tripodal N,O ligands, tpa (tris[(2-pyridyl)methyl]amine) and tpaam (tris[6-((2-N,N-diethylcarbamoyl)pyridyl)methyl]amine) are studied in water. The analysis of the proton lanthanide induced NMR shifts indicate that there is no abrupt structural change in the middle of the rare-earth series. Unexpectedly, the formation constant values of the lanthanide podates of tpaam and tpa in D2O at 298 K are similar, suggesting that the addition of the three amide groups to the ligand tpa does not lead to any increase in stability of the lanthanide complexes of tpaam in respect to tpa, even though the amide groups are coordinated to the metal in aqueous solution. The measurement of the enthalpy and entropy changes of the complexation reactions shows that the two similar ligands tpa and tpaam have different driving forces for lanthanide complexation. Indeed, the formation of tpa podates benefits from an exothermic enthalpy change associated with a small entropy change, whereas the complexation reaction with tpaam is clearly entropy-driven though opposed by a positive enthalpy change. The hydration states of the europium complexes were measured by luminescence and show the coordination of 4-5 water ligands in [Eu(tpa)]3+ whereas there are only 2 in [Eu(tpaam)]3+. Therefore the heptadentate ligand tpaam releases the translational entropy of more water molecules than does the tetradentate ligand tpa.


New potential cytotoxic and antitumor substances. II. Effect of hydroxyanthraquinones and their glucosides on Ehrlich ascites carcinoma cells in vitro.
Mono and dihydroxyanthraquinones and their derivatives affected the utilization of 14C-labeled precursors nucleic acid and protein synthesis into Ehrlich ascites carcinoma (EAC) cells. Inhibitory effect of the substances markedly increased when one acetyl group was introduced into the basic molecule. As the tested substances inhibited mainly incorporation of 14C uridine into the cold TCA insoluble fraction of EAC cells, their mechanism of action can be explained by the inhibition of RNA synthesis.


Novel system for reducing leaching of the herbicide metribuzin using clay-gel-based formulations.
Metribuzin is an herbicide widely used for weed control that has been identified as a groundwater pollutant. It contaminates the environment even when it is used according to the manufacturer's instructions. To reduce herbicide leaching and increase weed control, new controlled release formulations were developed by entrapping metribuzin within a sepiolite-gel-based matrix using two clay/herbicide proportions (0.5/0.2 and 1/0.2) (loaded at 28.6 and 16.7% a.i.) as a gel (G28, G16) or as a powder after freeze-drying (LF28, LF16). The release of metribuzin from the control released formulations into water was retarded, when compared with commercial formulation (CF) except in the case of G28. The mobility of metribuzin from control released formulations into soil columns of sandy soil was greatly diminished in comparison with CF. Most of the metribuzin applied as control released formulations (G16, LF28 and LF16) was found at a depth of 0-8 cm depth. In contrast, residues from CF and G28 along the column were almost negligible. Bioassays from these control released formulations showed high efficacy at 0-12 cm depth. The use of these novel formulations could minimize the risk of groundwater contamination while maintaining weed control for a longer period.


Slit stimulation recruits Dock and Pak to the roundabout receptor and increases Rac activity to regulate axon repulsion at the CNS midline.
Drosophila Roundabout (Robo) is the founding member of a conserved family of repulsive axon guidance receptors that respond to secreted Slit proteins. Here we present evidence that the SH3-SH2 adaptor protein Dreadlocks (Dock), the p21-activated serine-threonine kinase (Pak), and the Rac1/Rac2/Mtl small GTPases can function during Robo repulsion. Loss-of-function and genetic interaction experiments suggest that limiting the function of Dock, Pak, or Rac partially disrupts Robo repulsion. In addition, Dock can directly bind to Robo's cytoplasmic domain, and the association of Dock and Robo is enhanced by stimulation with Slit. Furthermore, Slit stimulation can recruit a complex of Dock and Pak to the Robo receptor and trigger an increase in Rac1 activity. These results provide a direct physical link between the Robo receptor and an important cytoskeletal regulatory protein complex and suggest that Rac can function in both attractive and repulsive axon guidance.


Time of farmers' exposure to biological factors in agricultural working environment.
Working time in conditions of exposure to hazardous factors is an important element indispensable for the evaluation of human exposure in the working environment. Agricultural work is accompanied by co-occurrence of many risk factors threatening farmers' health, e.g. dust, elements of the thermal environment, noise, vibration, chemical and biological agents. Biological factors cause diseases with contagious, allergic or immuno-toxic backgrounds which constitute the majority of farmers' occupational diseases registered in Poland. Exposure to hazardous factors in agricultural working environment is due to contact with plants, animals and organic wastes, more precisely--with microbes, plant and animal particles present in aerogenic agricultural dust, as well as pathogens of contagious and invasive diseases present in contaminated soil, water and plants. Data concerning the duration of farmers' exposure to biological and other factors of the working environment were obtained with the use of the Private Farmer Work Chart. Time-schedule observations concerned an annual work cycle. The study covered 30 farms with the following production profiles: plant (Group A), animal (Group B) and mixed production (Group C). The total working time was: in Group A - from 106-163 % of the legal working time; in Group B - from 75-147 %; in Group C - from 136-167 %. Among 48 work activities contributing to the full working cycle among the farmers examined, 15 activities were accompanied by 5 factors. These were mainly field activities which covered plant harvesting and fertilizing, chemical plant protection, as well as cultivation activities. Agricultural dust and elements of the thermal environment were the environmental factors most frequently accompanying agricultural work, followed by contact with biological factors, noise, vibration, and chemical agents. Biological factors are a specific element associated with 19 work activities, mainly the spreading of manure, animal breeding and plant harvesting. Farmers' working time in conditions of exposure to these factors in the group of plant producers was 51 % of the total working time on average, among animal breeders--80 % and in the case of mixed production--77 %.


[Implicit Associations with Death: First Validation of the German Version of the Suicide Implicit Association Test (Suicide IAT)].
Nock, Park, Finn, et al. 1 developed an implicit association test for suicide (suicide IAT) measuring the implicit association between 'death' and 'self'. They demonstrated that psychiatric patients, who already attempted suicide, showed stronger implicit associations with 'death' than with 'life' compared to patients without suicide attempt history. The present study had 2 aims: (1) to present a new German version of the suicide IAT and provide its first validation and (2) to investigate how implicit associations (suicide IAT) relate to suicidal ideation and behaviour, well-known risk factors such as depressiveness and hopelessness, and central concepts of the Interpersonal Theory of Suicide 2, Thwarted Belongingness and Perceived Burdensomeness. The sample consisted of 16 patients with a current Major Depression and suicidal ideation as well as 16 non-depressive, non-suicidal controls. Patients showed stronger associations between 'death' and 'self' than controls. We further found positive correlations between implicit associations with death and explicitly self-reported suicidal behaviour - controlled for depressiveness, hopelessness, and suicidal ideation. Our results confirm the validity of the German version of the suicide IAT and are discussed in the light of the Interpersonal Theory of Suicidal Behaviour 2 and recent suicide research.


Effects of remifentanil and remifentanil-alfentanil administration on emergence agitation after brief ophthalmic surgery in children.
Sevoflurane is commonly usedin pediatric anesthesia due to its non-irritating airway properties, and rapid induction and emergence. However, it is associated with emergence agitation (EA) in children. EA may cause injury to the child or damage to the surgical site and is a cause of stress to both caregivers and families. The efficacy of remifentanil and additional alfentanil on EA in the pediatric patients underwent ophthalmic surgery with sevofluraneanesthesiawas not well evaluated to date. This study was designed to compare the effects of remifentanil and remifentanil plus alfentanil on EA in children undergoing ophthalmic surgery with sevofluraneanesthesia. Children (aged 3-9 years) undergoing ophthalmic surgery undersevoflurane anesthesia were randomly assigned to group S (sevoflurane alone), group R (sevofluraneandremifentanil infusion, 0.1 μg/kg/min), or group RA (sevoflurane withremifentanil infusion and intravenous injection of alfentanil 5 μg/kg 10 min before the end of surgery). Mean arterial pressure (MAP), heart rate (HR), and sevoflurane concentration were checked every 15 min after induction of anesthesia. The incidence of EA, time to extubation from discontinuation of sevoflurane inhalation, and time to discharge from the postanesthesia care unit was assessed. The incidence of EA was significantly lower in groups R (32 %, 11/34; P = 0.01) and RA (31 %, 11/35; P = 0.008) than group S (64 %, 21/33). The time to extubation was prolonged in group RA (11.2 ± 2.3 min; P = 0.004 and P = 0.016) compared with groups S (9.2 ± 2.3 min) andR (9.5 ± 2.4 min). MAP and HR were similar in all three groups, apart from a reduction in HR at 45 min in groups R and RA. However, the sevoflurane concentration was lower in groups R and RA than group S (P < 0.001). The administration of remifentanil to children undergoing ophthalmic surgery undersevoflurane anesthesia reduced the incidence of EA without clinically significant hemodynamic changes. However, the addition of alfentanil(5 μg/kg)10 min before the end of surgery provided no additional benefit compared withremifentanil alone. NCT02486926 , June.29.2015.


Adaptation of the Mental Health Inventory (MHI-38) for Adolescents - Indonesian Version.
This study validates the Indonesian version of the Mental Health Inventory-38 (MHI-38) for use among Indonesian adolescents. The adaptation process followed guidelines from the International Test Commission and involved translation, expert review, cognitive interviews, and psychometric evaluation. A total of 562 adolescents (mean age = 15.42, SD = 1.84) participated in the study. The MHI-38 demonstrated dual factors: psychological well-being and psychological distress. Internal consistency was high for the MHI-38 (α = 0.892) and its factors: psychological well-being (α = 0.894) and psychological distress (α = 0.952). Confirmatory factor analysis indicated a good fit (RMSEA = 0.048, CFI = 0.945, NFI = 0.908, TLI = 0.929). Psychological well-being correlated moderately with the Satisfaction with Life Scale (r = 0.469, p = 0.00) and positive affect (r = 0.448, p = 0.00), but negatively with the Kessler Psychological Distress Scale (r = -0.230, p = 0.00). Psychological distress correlated strongly with the Kessler Psychological Distress Scale (r = 0.910, p = 0.00) and negative affect (r = 0.857, p = 0.00), but negatively with the Satisfaction with Life Scale (r = 0.556, p = 0.00). The Indonesian version of the MHI-38 demonstrated good psychometric properties and validity, making it a reliable tool for assessing mental health in Indonesian adolescents.


Reflectance confocal microscopy in paediatric patients: Applications and limits.
Reflectance confocal microscopy (RCM) is a non-invasive diagnostic tool extensively studied for adult patients. In this retrospective case series conducted at the Dermatology Unit of the University of Campania, Naples, Italy, all patients under 19 years old who were submitted to RCM from January 2011 to December 2021 where evaluated. The aim of the study was to review the most usual indications and possible benefits that it might add for children. Data collection included 215 patients (86 males and 129 females, mean age: 12). Most of the exams (n = 85; 39.5%) were performed for lesions clinically compatible with Spitz nevi, congenital nevi (n = 50 23,2%) and atypical melanocytic lesions (n = 46; 21%) among which two melanomas were detected. RCM can be an useful instrument when evaluating paediatric patients and may help avoid unnecessary biopsy in most cases, representing an additional instrument to improve diagnostic accuracy.


Effects of feeding bacterial lipopolysaccharide and dextran sulphate on the development of oral tolerance to contact sensitizing agents.
The effect of feeding the B-cell mitogens Escherichia coli lipopolysaccharide and dextran sulphate on the development of orally induced tolerance to the contact sensitizing agent picryl chloride was studied in mice. Feeding either agent throughout the experiment or during tolerization, increased the tolerizing effect of a single feed of picryl chloride.


[Effect of ceramic thickness and resin cement shades on final color of heat-pressed ceramic veneers].
Objective: To analyze the effect of ceramic materials thickness and resin cement shades on the final color of ceramic veneers in the discolored teeth, and to investigate the color agreement of try-in pastes to the corresponding resin cements. Methods: Sixty artificial maxillary central incisor teeth (C2 shade) were used to simulate the natural discolored teeth and prepared according to veneer tooth preparation protocol. Veneers of different thickness in the body region (0.50 and 0.75 mm) were fabricated using ceramic materials (LT A2 shade, IPS e.max Press). The ceramic veneer specimens were bonded to the artificial teeth using the 6 shades of resin cements (Variolink Veneer: shades of LV-3, LV-2, HV+3; RelyX™ Veneer: shades of TR, A3, WO) (n=5). A clinical spectrophotometer was used to measure the color parameters of ceramic veneers at the cervical, body and incisal regions. Color changes of veneers before and after cementation were calculated and registered as ΔE1, and the changes between try-in paste and the corresponding resin cements were registered as ΔE2. Results: Three-way ANOVA indicated that ΔE1 and ΔE2 values were significantly affected by the ceramic thickness, resin cement shades and measuring regions (P<0.05). The ΔE1 values of six shades ranged from 0.59-8.27. The ΔE1 values were more than 2.72 when the ceramic veneers were cemented with resin cements in shades of HV+3 and WO. The ΔE2 values of six shades ranged from 0.60-2.56. The shades of HV+3, WO and A3 resin cements were more than 1.60. Conclusions: Different thickness of ceramic materials, resin cement shades and measuring regions could affect the final color of ceramic veneers. The color differences of some resin cements and corresponding try-in pastes might be observed in clinical practice.


Biologics for chronic spontaneous urticaria: toward a personalized treatment.
Chronic spontaneous urticaria (CSU) is characterized by the recurrent occurrence of short-lived wheals with or without angioedema for more than 6 weeks. Although its pathogenesis is not completely defined, several mechanisms seem involved, including autoimmunity and autoallergy with complement and coagulation activation. Various biologics are currently available or under investigation to counteract different CSU pathomechanisms. The recent literature dealing with biologics in the treatment of CSU was screened and analyzed; the different treatments were divided into anti-IgE and other than anti-IgE biologics. The latter were subdivided according to their target mechanisms. Biologic drugs exert their effects in a very precise and specific manner. A majority of patients (arguably those with type I disease) respond to anti-IgE treatment. Others, possibly with type IIa disease, show a slow response to anti-IgE drugs. Things are much more complicated in anti-IgE-refractory patients. Some respond well to nonspecific immune suppressors, such as corticosteroids and cyclosporin suggesting that an immune-mediated pathogenic mechanism, not involving the high-affinity IgE receptor, is probably active. Several ongoing studies are evaluating biologics and small molecules counteracting other pathomechanisms, including anti-receptor biologics, Bruton tyrosine kinase (BTK) inhibitors, mast cell targets, and specific cytokines.


Absence of Cytotoxicity towards Microglia of Iron Oxide (α-Fe2O3) Nanorhombohedra.
Understanding the nature of interactions between nanomaterials, such as commercially ubiquitous hematite (α-Fe2O3) Nanorhombohedra (N-Rhomb) and biological systems is of critical importance for gaining insight into the practical applicability of nanomaterials. Microglia represent the first line of defense in the central nervous system (CNS) during severe injury or disease such as Parkinson's and Alzheimer's disease as illustrative examples. Hence, to analyze the potential cytotoxic effect of nanorhombohedra exposure in the presence of microglia, we have synthesized Rhodamine B (RhB) labeled-α-Fe2O3 N-Rhomb, with lengths of 47 ± 10 nm and widths of 35 ± 8 nm. Internalization of RhB labeled-α-Fe2O3 N-Rhomb by microglia in the mouse brain was observed, and a dose-dependent increase in the cellular iron content as probed by cellular fluorescence was detected in cultured microglia after nanoparticle exposure. The cells maintained clear functional viability, exhibiting little to no cytotoxic effects after 24 and 48 hours at acceptable, physiological concentrations. Importantly, the nanoparticle exposure did not induce microglial cells to produce either tumor necrosis factor alpha (TNFα) or interleukin 1-beta (IL1β), two pro-inflammatory cytokines, nor did exposure induce the production of nitrites and reactive oxygen species (ROS), which are common indicators for the onset of inflammation. Finally, we propose that under the conditions of our experiments, i.e. in the presence of RhB labeled-α-Fe2O3 N-Rhomb maintaining concentrations of up to 100 µg/mL after 48 hours of incubation, the in vitro and in vivo internalization of RhB labeled-α-Fe2O3 N-Rhomb are likely to be clathrin-dependent, which represents a conventional mechanistic uptake route for most cells. Given the crucial role that microglia play in many neurological disorders, understanding the potential cytotoxic effects of these nanostructures is of fundamental importance if they are to be used in a therapeutic setting.


Human endometrial stromal cell rho GTPases have opposing roles in regulating focal adhesion turnover and embryo invasion in vitro.
Implantation of the embryo into the uterine compartment is a multistep event involving attachment of the embryo to the endometrial epithelia, followed by invasion of the embryo through the endometrial stroma. RHOA, RAC1, and CDC42 are members of the Rho GTPase family of proteins, which control cell functions such as cell migration and cytoskeletal reorganization. Herein, using a heterologous in vitro coculture model, we show that implantation of mouse blastocysts into human endometrial stromal cells (hESCs) is regulated by Rho GTPase activity in hESCs. Whereas iRNA-mediated silencing of RAC1 expression in hESCs led to inhibition of embryo implantation, silencing of either RHOA or CDC42 in hESCs promoted embryo implantation in coculture assays. Analysis of downstream signaling pathways demonstrated that RAC1 silencing was associated with decreased focal adhesion disassembly and resulted in large focal adhesion complexes in hESCs. In contrast, RHOA or CDC42 silencing resulted in perturbed focal adhesion assembly, leading to a decrease in the number of focal adhesions observed. Furthermore, inhibition of Rho signaling using a Rho kinase inhibitor, Y27632, led to decreased activation of protein tyrosine kinase 2 (PTK2, also called focal adhesion kinase) and decreased focal adhesion assembly. Importantly, perturbation of focal adhesion turnover in hESCs, mediated by PTK2 silencing, resulted in inhibition of embryo implantation into hESC monolayers. These findings suggest that Rho GTPase-PTK2-dependent remodeling of the endometrial stromal cell compartment may be critical for successful embryo implantation.


EVOLUTION OF MULTIPLE KINDS OF FEMALE SPERM-STORAGE ORGANS IN DROSOPHILA.
Females of all species belonging to the family Drosophilidae have two kinds of sperm-storage organs: paired spherical spermathecae and a single elongate tubular seminal receptacle. We examined 113 species belonging to the genus Drosophila and closely allied genera and describe variation in female sperm-storage organ use and morphology. The macroevolutionary pattern of organ dysfunction and morphological divergence suggests that ancestrally both kinds of organs stored sperm. Loss of use of the spermathecae has evolved at least 13 times; evolutionary regain of spermathecal function has rarely if ever occurred. Loss of use of the seminal receptacle has likely occurred only once; in this case, all descendant species possess unusually elaborate spermathecae. Data further indicate that the seminal receptacle is the primary sperm-storage organ in Drosophila. This organ exhibits a pattern of strong correlated evolution with the length of sperm. The evolution of multiple kinds of female sperm-storage organs and the rapidly divergent and correlated evolution of sperm and female reproductive tract morphology are discussed.


Aryne Compatible Solvents are not Always Innocent.
Arynes are important and versatile intermediates in a variety of transformations. Commonly used solvents for aryne chemistry include acetonitrile and dichloromethane. Although rarely reported, the reactive nature of aryne intermediates makes them prone to side reactions, which sometimes involve solvent participation. Acetonitrile and dichloromethane are not always innocent solvents and can participate in aryne-based reactions. These results are presented in the context of ongoing mechanistic investigations of the triple aryne-tetrazine reaction.


Protocol for high-sensitivity/long linear-range spectrofluorimetric DNA quantification using ethidium bromide.
Ethidium bromide (EtBr) is the most widely used fluorescent dye in nucleic acid gel electrophoresis since decades. However it has been essentially forgotten in DNA quantification by spectrofluorimetry. While investigating sensitivity and dynamic range of available fluorochromes, we found that EtBr permits much more sensitive fluorimetric measurements than previously thought. We report here a revised, accurate, and easy-to-use protocol for EtBr-based DNA quantification in solution, which usefully complements the widely used indirect quantification on agarose gels.


Active photosensitizers in butter detected by fluorescence spectroscopy and multivariate curve resolution.
In this study, fluorescence excitation and emission matrices and multivariate curve resolution (PARAFAC) were used to detect and characterize active photosensitizers spectrally in butter. Butter samples were packed under high (air) and low oxygen (<0.05%) atmospheres and exposed to violet, green, or red light. Six photosensitizers were found: riboflavin, protoporphyrin, hematoporphyrin, a chlorophyll a-like molecule, and two unidentified tetrapyrrols. By estimation of relative concentrations, we could follow how each sensitizer was photodegraded as function of wavelength, oxygen level, and time. The degradation rate of protoporphyrin, hematoporphyrin, chlorophyll a, and one of the tetrapyrrols correlated well (0.83-0.91) with the formation of sensory measured oxidation. The results suggest that mainly type I photoreactions were responsible for the degradation of photosensitizers in both high and low oxygen atmosphere. Type II photoreactions (generation of singlet oxygen) were involved in the oxidation of butter stored in air. The study shows that PARAFAC modeling of fluorescence landscapes is an excellent tool for studying photooxidation in complex systems.


[Exogenous carbon monoxide protects against liver injury induced by ischemia/reperfusion of hind limbs in rats].
To investigate the protective effect of exogenous carbon monoxide (CO) on the liver injury induced by ischemia/reperfusion (I/R) of hind limbs in rats. 100 SD rats were divided randomly into sham operated group (S), S+ CO group (SC), I/R group (I/R), I/ R+ CO group (RC). A rat model of ischemia in hind limbs and the reperfusion liver injury was established with the occlusion of the femoral arteries for 4 h and re-opening for 6 - 72 h, 10 d. The rats in SC and RC groups were exposed to air containing CO (the volume traction of CO: 0.05%) for 2 h before and after reperfusion or the corresponding control time point, while the other two groups were exposed to the routine air. The pathologic changes of liver tissue were morphologically observed by HE stain. Serum GPT activity was tested by Automatic Biochemical Analyzer. The percentage of apoptosis, expression levels of bax and bcl-2 protein in liver tissue were detected by Flow Cytometry. There was no difference between S and SC groups. Compared with SC group: (1) Pathological changes in liver tissue were significant in I/R and RC groups. (2) The serum GPT activity of I/R and RC groups was obviously increased. (3) In IR and RC groups, the percentage of apoptosis in liver tissue was all significantly increased. (4) The bax expression level was significantly increased. Compared RC group with I/R group: (1) Pathological change was slight. (2) The serum GPT activity was depressed. (3) The percentage of apoptosis and expression level of bax protein in liver tissue were depressed. (4) The expression level of bcl-2 protein in liver tissue was increased. Exogenous CO could attenuate liver tissue injury induced by limbs I/R in rats.


Endoloop closure following gastric endoscopic submucosal dissection to prevent delayed bleeding in patients receiving antithrombotic therapy.
Given the high risk of bleeding in post-endoscopic submucosal dissection (ESD) patients receiving antithrombotic therapy, a new effective method is needed to prevent delayed bleeding among such patients. The aim of this study was to assess the efficacy of endoloop closure, using an endoloop and clips, after gastric ESD to prevent bleeding among patients receiving antithrombotic therapy. This retrospective study enrolled patients taking antithrombotic agents who underwent ESD for early gastric cancer between March 2016 and January 2019. Patients were classified into two groups: the endoloop closure group and the control group (no prophylactic treatment). We compared the rates of post-endoscopic submucosal dissection bleeding between the two groups. Overall, 178 patients were included, with 37 patients in the endoloop closure group and 141 patients in the control group. The rate of post-endoscopic submucosal dissection bleeding was in general lower in the endoloop closure group than in the control group; however, the difference was not statistically significant (8% vs. 23%, p = 0.06). Among patients with a resected specimen size <40 mm and those using multiple antithrombotic agents, the endoloop closure group showed a lower rate of post-endoscopic submucosal dissection bleeding (0% vs. 16%, p = 0.03 and 10% vs. 70%, p = 0.02, respectively). Closure using an endoloop and endoclips after gastric ESD might prevent post-procedure bleeding in patients receiving antithrombotic therapy, particularly in those patients with a resected specimen <40 mm and those receiving multiple antithrombotic agents.


Rab11-FIP2 functions in transferrin recycling and associates with endosomal membranes via its COOH-terminal domain.
Rab11-FIP2 is a recently described member of the Rip11/Rab11-FIP/Rab coupling protein family of Rab11 interacting proteins. Rab11-FIP2 interacts with both Rab11 and myosin Vb and co-localizes with Rab11 in both HeLa and Madin-Darby canine kidney cells (Hales, C. M., Griner, R., Hobdy-Henderson, K. C., Dorn, M. C., Hardy, D., Kumar, R., Navarre, J., Chan, E. K., Lapierre, L. A., and Goldenring, J. R. (2001) J. Biol. Chem. 276, 39067-390751). Here, we characterized the specificity of the interaction between Rab11-FIP2 and Rab11 and report that it does not interact with Rab4, Rab3, Rab5, Rab6, or Rab7. We demonstrate that the COOH-terminal region of Rab11-FIP2, which contains the Rab11 binding domain (RBD), is necessary and sufficient for its early endosomal membrane association. In contrast, the amino-terminal region, which contains a phospholipid binding C2-domain, by itself was insufficient for membrane binding. Expression of a deletion mutant of Rab11-FIP2, containing the RBD, caused tubulation of a transferrin receptor-positive early endosomal compartment in HeLa cells. Endogenous Rab11 was also associated with this compartment. This phenotype cannot be reversed by excess wild-type Rab11, or dominant-positive Rab11 (Rab11Q70L), suggesting that Rab11-FIP2 functions downstream of Rab11 in endosomal trafficking.


Involvement of activation of ATP-dependent potassium channels in ischemic preconditioning in swine.
This study evaluated the importance of ATP-dependent potassium channels (KATP) for ischemic preconditioning (IP) in swine. Swine were studied because due to the sparsity of their innate collateral circulation infarct size (IS) development closely resembles that observed in humans. Ninety minutes of ischemia at a blood flow reduction sufficient to reduce regional myocardial work by 90% caused 13.2 +/- 8.9% (SD) IS of the area at risk. A single cycle of 10-min preconditioning ischemia followed by 15-min reperfusion reduced IS after 90 min of ischemia to 2.8 +/- 2.7%. The epicardial monophasic action potential duration at 50% repolarization (MAP50) was decreased more markedly during the initial 10 min of the prolonged ischemia than during the first 10 min of the preconditioning ischemic period (84 +/- 4 vs. 89 +/- 2%). Transmural myocardial adenosine (ADO) uptake was reversed to net release during both ischemic periods and during the initial phase of reperfusion. Glibenclamide (0.5 mg/kg, followed by 50 micrograms/min i.v.) abolished the reduction in MAP50 without altering ADO release. Glibenclamide did not alter IS per se (13.0 +/- 7.6%) but abolished the beneficial effect of IP (IS: 13.6 +/- 6.2%). Thus blockade of KATP with glibenclamide abolishes the IS-reducing effect of IP in swine but does not reduce ADO release.


Bach2 regulates AID-mediated immunoglobulin gene conversion and somatic hypermutation in DT40 B cells.
The transcription factor Bach2 is required for germinal center formation, somatic hypermutation (SHM), and class-switch recombination (CSR) of immunoglobulins. SHM and CSR are initiated by activation-induced cytidine deaminase (AID) which has potential to induce human B cell lymphoma. To understand the role of Bach2 in AID-mediated immunoglobulin gene diversification processes, we established a BACH2-deficient DT40 B cell line. We show that in addition to allowing SHM, Bach2 drives immunoglobulin gene conversion (GCV), another AID-dependent antibody gene diversification process. We demonstrate that Bach2 promotes GCV by increasing the expression of AID. Importantly, we found that the regulation of AID is independent of Blimp-1 and that BACH2-deficient cells have altered expression of several genes regulating AID expression, stability and function. Furthermore, re-expression of BACH2 or AID in Bach2KO cells restored the SHM and GCV defects. These results demonstrate that Bach2 has a previously unappreciated role in the production of high-affinity antibodies.


Autophagy and protein turnover signaling in slow-twitch muscle during exercise.
The aim of this study was to characterize skeletal muscle protein breakdown and mitochondrial dynamics markers at different points of endurance exercise. Mice run at 10 m·min(-1) during 1 h, and running speed was increased by 0.5 m·min(-1) every minute during 40 min and then by 1 m·min(-1) until exhaustion. Animals were killed by cervical dislocation at 30, 60, 90, and 120 min; at time to exhaustion (Te); and at 3 and 24 h during recovery. The soleus and the deep red regions of the quadriceps muscles were pooled. AMPK phosphorylation (Thr172) increased from 30 min to Te, and FoxO3a phosphorylation (Thr32 and Ser253) decreased from 120 min to 3 h after exercise. FoxO3a-dependent E3 ligases Mul1 and MuRF1 proteins increased from 30 min to Te and at Te and 3 h after exercise, respectively, whereas MAFbx/atrogin-1 protein expression did not change significantly. The autophagic markers LC3B-II increased at 120 min and Te, and p62 significantly decreased at Te. The AMPK-dependent phosphorylation of Ulk1 at Ser317 and Ser555 increased from 60 min to Te and at 30 and 60 min, respectively. Akt (Ser473), MTOR (Ser2448), and 4E-BP1 (Thr37/46) phosphorylation decreased from 90 min to Te, and the MTOR-dependent phosphorylation of Ulk1 (Ser757) decreased from 120 min to Te. Ser616 phosphorylation of the mitochondrial fission marker DRP1 increased from 60 min to Te, but protein expression of the fusion markers mitofusin-2, a substrate of Mul1, and OPA1 did not significantly change. These results fit with a regulation of protein breakdown triggered by FoxO3a and Ulk1 pathways after AMPK activation and Akt/MTOR inhibition. Furthermore, our data suggest that mitochondrial fission is quickly increased, and mitochondrial fusion is unchanged during exercise.


Which experimental systems should we use for human microbiome science?
Microbiome science is revealing that the phenotype and health of animals, including humans, depend on the sustained function of their resident microorganisms. In this essay, I argue for thoughtful choice of model systems for human microbiome science. A greater variety of experimental systems, including wider use of invertebrate models, would benefit biomedical research, while systems ill-suited to experimental and genetic manipulation can be used to address very limited sets of scientific questions. Microbiome science benefits from the coordinated use of multiple systems, which is facilitated by networks of researchers with expertise in different experimental systems.


GRADUAL CHANGE IN HUMAN TOOTH SIZE IN THE LATE PLEISTOCENE AND POST-PLEISTOCENE.
Starting with the onset of the last glaciation approximately 100,000 years ago and continuing to the end of the Late Pleistocene approximately 10,000 years ago, human tooth size began to reduce at a rate of 1% every 2,000 years. Both the mesial-distal and the buccal-lingual dimensions of mandibular and maxillary teeth were undergoing the same rate of reduction. From the beginning of the Post-Pleistocene until the present, the overall rate of dental reduction doubled, becoming approximately 1% per thousand years. Buccal-lingual dimensions are now reducing twice as fast as mesial-distal dimensions, and maxillary teeth are reducing at an even more rapid rate than mandibular teeth. Late Pleistocene rates are comparable in Europe and the Middle East. The Post-Pleistocene rates are also the same for Europe, the Middle East, China, Japan, and Southeast Asia. It is suggested that the cookery at the beginning of the Late Pleistocene allowed the earlier changes to occur. The use of pottery within the last 10,000 years further reduced the amount of selection that had previously maintained usable tooth substance. Reduction then occurred as a consequence of the Probable Mutation Effect (Brace, 1963; McKee, 1984).


Ratio of thyroxine to thyroxine-binding globulin. An assessment of the validity of a single reference range.
The thyroxine:thyroxine-binding globulin ratio in serum (T4:TBG) has been proposed as a measure of thyroid status unaffected by altered binding protein levels. Here 320 apparently euthyroid patients are used to derive euthyroid ranges for serum thyroxine concentrations at specific TBG levels. These ranges are compared with those predicted by a T4:TBG reference range derived from the same patient data. The comparison suggests that the ratio would give false positives for hyperthyroidism at low TBG levels and false negatives at high TBG levels. To overcome this the use of graphical reporting of results or the relation of patient results to empirical reference ranges appropriate to the TBG level is suggested.


Ginsenoside Rh4 Improves Hepatic Lipid Metabolism and Inflammation in a Model of NAFLD by Targeting the Gut Liver Axis and Modulating the FXR Signaling Pathway.
Non-alcoholic fatty liver disease (NAFLD) is a series of disorders of liver metabolism caused by the accumulation of lipids in the liver, which is considered the main cause of hepatocellular carcinoma. Our previous study demonstrated the promising efficacy of ginsenoside Rh4 in improving the intestinal tract and its related metabolites. Meanwhile, many studies in the literature have investigated the gut microbiota and its metabolites, such as bile acids (BAs) and short-chain fatty acids (SCFAs), which play a key role in the pathogenesis of NAFLD. Therefore, this study focused on whether Rh4 could achieve therapeutic effects on NAFLD through the gut-liver axis. The results showed that Rh4 exhibited sound therapeutic effects on the NAFLD model induced by the Western diet and CCl4 in mice. In the liver, the degrees of hepatic steatosis, lobular inflammation levels, and bile acid in the liver tissue were improved after Rh4 treatment. At the same time, Rh4 treatment significantly increased the levels of intestinal SCFAs and BAs, and these changes were accompanied by the complementary diversity and composition of intestinal flora. In addition, correlation analysis showed that Rh4 affected the expression of proteins involved in the farnesoid X receptor (FXR) signaling pathway in the liver and intestine, which modulates hepatic lipid metabolism, inflammation, and proteins related to bile acid regulation. In conclusion, our study provides a valuable insight into how Rh4 targets the gut-liver axis for the development of NAFLD, which indicates that Rh4 may be a promising candidate for the clinical therapy of NAFLD.


Immune complexes in chronic hepatitis.
Rheumatoid factors were present in 33.2%, crioglobulins in 47.6%, and anticomplementary assay in 34.2% of cases with chronic active hepatitis. No statistically significant loss of total complement was observed, but its components especially C1 and C3, exhibited lowered titers in 48.6% and respectively 45.7% of 160 cases. The origin, significance and pathogenicity of these factors are discussed in connection with the presence and possible role of the immunologic complexes to the development of chronic liver injury.


[Teratoma of umbilical cord: a case report and literature review].
Teratomas are tumors that arise from totipotent embryonic germ cells. The umbilical cord is an extremely rare site for this tumor, only 12 cases have been reported in the medical literature. Herein we describe an umbilical cord mass presenting necrosis with clinical and histopathological features that can be considered as another case of umbilical cord teratoma. We discuss the differential diagnosis and review the complete literature on this subject.


Esophageal transit scintigraphy--a cautionary note.
Esophageal transit scintigraphy and esophageal manometry were compared in forty-two patients with symptoms of esophageal disease. Fifteen healthy volunteers were studied as a control group for the scintigraphic investigation. Agreement between the tests was present in 79% of patients. In all the five patients in whom the esophageal manometry was abnormal and the esophageal transit study was normal, the manometric finding was "giant esophageal contractions." In four of the control group an abnormal transit pattern was observed on one of two esophageal studies. Esophageal transit scintigraphy has some limitations as a screening test for esophageal motor dysfunction.


Dealing with technical challenges in embolization of a rare aberrant left inferior bronchial artery arising from the left gastric artery in a patient with massive hemoptysis.
Bronchial artery embolization is an established intervention for management of recurrent massive hemoptysis in a majority of patients. The source of bleeding in a majority of cases is systemic arteries - orthotopic bronchial arteries, anomalous bronchial arteries, or nonbronchial systemic collaterals. We report a case of an aberrant left inferior bronchial artery arising from the left gastric artery (LGA) in a patient with massive hemoptysis. Such origin from infradiaphragmatic vessels and specially left gastric arteries is very rare and needs to be considered by interventional radiologists and pulmonologists in case with hemoptysis disproportionate to supply by orthotopic arteries. Technical challenges were present in the present case in the form of an aneurysm in the aberrant artery and nontarget hepatic and gastric branches arising from LGA. Appropriate selection of hardware and embolic agents was done to deal with the clinical situation.


The impact of latitude on the prevalence of seasonal depression.
This study sought to determine whether the prevalence of the seasonal subtype of major depression (SAD) in the community varied as a function of latitude. Random telephone numbers were generated across 8 degrees of latitude (41.5 degrees N to 49.5 degrees N) for the province of Ontario. Eight strata of 1 degree each were sampled equally throughout a 12-month period. Using a validated and structured diagnostic interview, we interviewed by telephone respondents over 20 years of age who had lived in the region for 3 years or more. We evaluated patterns of symptom change across seasons to establish a diagnosis of SAD according to DSM-IV criteria. Of the 2078 households that were assessed for eligibility, 1605 (77%) completed the interview. The crude prevalence of lifetime SAD was 2.6% (95% CI, 1.9 to 3.5). There was no impact of latitude on prevalence of either major depression or the seasonal subtype across the 8 strata, although the global measure of the severity of seasonal change in mood was significantly negatively correlated with latitude. SAD is a common subtype of major depression in Ontario, but there is no evidence to support an increase in prevalence with increasing latitude.


Early Warning Models to Predict the 90-Day Urinary Tract Infection Risk After Radical Cystectomy and Urinary Diversion for Patients With Bladder Cancer.
To develop and validate a nomogram of the 90-day urinary tract infection (UTI) risk for patients with bladder cancer undergoing radical cystectomy (RC) and urinary diversion. The predictive nomogram was based on a retrospective study on the consecutive patients who underwent RC and urinary diversion for bladder cancer between January 2014 and March 2021. The incidence and microbiology of UTI were reported. The univariate and multivariate logistic analyses were conducted to determine independent risk factors associated with UTI. The predictive accuracy and discriminatory ability of the established nomogram were evaluated by the concordance index (C-index) and decision curve analysis (DCA). The performance of the model was validated internally. A total of 220 patients were included and the incidence of UTI within 90 days was 27.3%. The most commonly identified pathogens were Enterococcus (42.0%), Escherichia coli (21.70%), and Candida (13.0%). Urinary diversion type, Charlson comorbidities index (CCI), stricture, and prognostic nutritional index (PNI) were included in the nomogram. The C-index of the nomogram for predicting UTI was 0.858 (95% CI: 0.593-0.953). In the validation cohort, the nomogram also showed high-predictive accuracy. Net reclassification improvement (NRI) and integrated discrimination improvement (IDI) index indicated that PNI led to improvement in predictive ability. The proposed early warning model shows great accuracy in predicting the incidence of 90-day UTI after RC and urinary diversion in patients with bladder cancer.


Serum transferrin receptors are decreased in the presence of iron overload.
To test the hypothesis that the quantities of circulating transferrin receptors are reduced in iron overload, we studied serum transferrin receptors and indirect measures of iron status in 150 subjects from rural Zimbabwe. We found significant inverse correlations between serum concentrations of transferrin receptors and ferritin, the ratio of ferritin to aspartate aminotransferase, and transferrin saturation (r > or = 0.44; P < 0.001). The mean +/- SD concentration of serum transferrin receptors in 23 subjects classified as having iron overload (ferritin > 300 microg/L and transferrin saturation > 60%) was 1.55 +/- 0.61 mg/L, significantly lower than the 2.50 +/- 0.62 mg/L in 75 subjects with normal iron stores (ferritin 20-300 microg/L and transferrin saturation 15-55%; P < 0.0005) and the 2.83 +/- 1.14 mg/L in 8 subjects with iron deficiency (ferritin < 20 microg/L; P = 0.001). In keeping with the regulation of transferrin receptor expression at the cellular level, our findings suggest that serum transferrin receptors are decreased in the presence of iron overload.


Perimembranous Ventricular Septal Defect Device Closure: Choosing Between Amplatzer Duct Occluder I and II.
Transcatheter closure of perimembranous ventricular septal defects (pmVSDs) is a well-established procedure. Recently, Amplatzer duct occluders (ADO) I and II have been reported to close large series of pmVSDs successfully (off-label use). ADOs are economical compared with the standard Amplatzer VSD occluders, a major consideration in developing countries with low-budget programs. We report closure of symptomatic, hemodynamically significant pmVSDs using the ADOI and ADOII devices. Although there are no set criteria for choosing between ADOI and ADOII, the former's price tag includes snare and long sheath. Thus, we aim to predetermine device usage based on transthoracic echocardiography (TTE) findings. Between March 2013 and November 2014, 30 patients had transcatheter closure of pmVSDs using the ADO devices. The median age was 4 years (range 1.1-13 years) and median weight was 15 kg (range 6.5-85 kg). ADOII could not be used in VSDs larger than 6 mm and/or with a large aneurysm. The median VSD size as assessed by echocardiography was 5.5 mm while the mean was 5.5 mm (range 3-12 mm); while by angiography it was 5 mm & the mean was 4.75 mm (range 3-9 mm). The median fluoroscopy time (FT) was 8 min (range 5-38 min). We inserted ADOI in 13 patients and ADOII in 17 patients (no significant difference between median age and weight in each group). VSD size was significantly larger and FT was longer in ADOI patients; the device type matched what was decided from TTE data in 84% of cases. Follow-up ranged from 2 to 24 months (median 12 months). The mean LVEDD z-score of the patients was 1.1 before VSD closure, while it was 0.63, 0.35, and 0.23 at the 1-, 3 months, and last follow-up, respectively. Complete closure rates immediately, at 24 h, and at last follow-up were 87, 90, and 94% respectively. No patient developed heart block or any other complication. ADOI and ADOII are equally safe and effective in pmVSD closure. ADOII use, although cheaper than ADOI, is limited to smaller VSDs. The choice between ADOI and ADOII can be decided by TTE prior to procedure which is convenient in low economic programs.


MiR-144-3p inhibits cell proliferation and induces apoptosis in multiple myeloma by targeting c-Met.
MicroRNA-144-3p (miR-144-3p) has been implicated in the development of many types of cancer. However, its role in multiple myeloma (MM) remains largely unknown. In this study, we found that miR-144-3p was downregulated in both MM cell lines and plasma from patients with MM. In vitro studies further showed that transfection of an miR-144-3p mimic into MM cells inhibited their proliferation and colony formation, and promoted cell cycle arrest at the G0/G1 phase and apoptosis. In addition, we found that miR-144-3p could directly target the 3'-untranslated region of cellular-mesenchymal to epithelial transition factor (c-MET) and suppress c-MET expression and its downstream signaling pathway (PI3K/AKT). Rescue experiments revealed that overexpression of c-MET partially reversed the inhibition effect of miR-144-3p in MM cells. In vivo studies confirmed that restoration of miR-144-3p suppressed tumor growth in xenograft nude mice by repressing c-MET. Overall, these findings demonstrate that miR-144-3p functions as a tumor suppressor in MM by targeting c-MET, suggesting that miR-144-3p might serve as a potential therapeutic target in MM.


[Effect of tumor promoting agents on the in vitro malignant transformation of the fetal rat brain cells exposed in utero to ethylnitrosourea].
The potent tumor promoter 12-0-tetradecanoyl phorbol 13-acetate (TPA) and phenobarbital (PB) were tested for their abilities to promote effect of these agents on the in vitro malignant transformation of the fetal rat brain cells exposed in utero to Ethylnitrosourea (ENU). Rat fetal brain cells were transferred to cultured system at 72 hours after single pulse of ENU (50 mg/kg B. W.) to pregnant SD-JCL rats on the 18th day of gestation. Primary cultured cells were divided into 20 groups, and graded doses of PB from 1.0 mM to 5.0 mM or that of TPA from 0.1 ng/ml to 50.0 ng/ml were added continuously into cultured medium. In the ENU group treated with TPA, it was found the results of more early appearance of "piled up focus" for about 90 days, more early capacity of colony formation in semisolid soft agar for about 110 days, and more early appearance of tumorigenicity for about 90 days than that in the ENU groups treated with or without acetone. An increased agglutinability to Concanavalin A (200 micrograms/ml) was appeared more early in the ENU groups treated with TPA than in the ENU groups. On the basis of these results, it is suggested that TPA promoted the in vitro malignant transformation of the fetal rat brain cells with a transplacental carcinogen of ENU, and TPA might effect as a tumor promoter on the neurogenic carcinogenesis. As for the mechanisms of the promoting effect of TPA, it is speculated that TPA might modulate the function of cell membrane from the results of Concanavalin A agglutinability, and might modulate the differentiation on cell function from the results of morphological analysis.


In-Depth Duodenal Transcriptome Survey in Chickens with Divergent Feed Efficiency Using RNA-Seq.
Since the feed cost is a major determinant of profitability in poultry industry, how to improve feed efficiency through genetic selection is an intriguing subject for breeders and producers. As a more suitable indicator assessing feed efficiency, residual feed intake (RFI) is defined as the difference between observed and expected feed intake based on maintenance and growth. However, the genetic mechanisms responsible for RFI in chickens are still less well appreciated. In this study, we investigated the duodenal transcriptome architecture of extreme RFI phenotypes in the six brown-egg dwarf hens (three per group) using RNA sequencing technology. Among all mapped reads, an average of 75.62% fell into annotated exons, 5.50% were located in introns, and the remaining 18.88% were assigned to intergenic regions. In total, we identified 41 promising candidate genes by differential expression analysis between the low and high RFI groups. Furthermore, qRT-PCR assays were designed for 10 randomly chosen genes, and nine (90.00%) were successfully validated. Functional annotation analyses revealed that these significant genes belong to several specific biological functions related to digestibility, metabolism and biosynthesis processes as well as energy homeostasis. We also predicted 253 intergenic coding transcripts, and these transcripts were mainly involved in fundamental biological regulation and metabolism processes. Our findings provided a pioneering exploration of biological basis underlying divergent RFI using RNA-Seq, which pinpoints promising candidate genes of functional relevance, is helpful to guide future breeding strategies to optimize feed efficiency and assists in improving the current gene annotation in chickens.