Diabetes and Hyperglycemia Affect Platelet GPIIIa Expression. Effects on Adhesion Potential of Blood Platelets from Diabetic Patients under In Vitro Flow Conditions.
Blood platelets play a crucial role in the early stages of atherosclerosis development. The process is believed to require firm adhesion of platelets to atherosclerosis-prone sites of the artery. However, little evidence exists regarding whether the blood platelets of individuals with pathological conditions associated with atherosclerosis have higher potential for adhesion. This process is to a large extent dependent on receptors present on the platelet membrane. Therefore, the aim of the presented study was to determine whether blood platelets from diabetic patients have higher capacity of adhesion under flow conditions and how diabetes affects one of the crucial platelet receptors involved in the process of adhesion-GPIIIa. The study compares the ability of platelets from non-diabetic and diabetic humans to interact with fibrinogen and von Willebrand factor, two proteins found in abundance on an inflamed endothelium, under flow conditions. The activation and reactivity of the blood platelets were also characterized by flow cytometry. Platelets from diabetic patients did not demonstrate enhanced adhesion to either studied protein, although they presented increased basal activation and responsiveness towards low concentrations of agonists. Platelets from diabetic patients were characterized by lower expression of GPIIIa, most likely due to an enhanced formation of platelet-derived microparticles PMPs, as supported by the observation of elevated concentration of this integrin and of GPIIIa-positive PMPs in plasma. We conclude that altered functionality of blood platelets in diabetes does not increase their adhesive potential. Increased glycation and decrease in the amount of GPIIIa on platelets may be partially responsible for this effect. Therefore, higher frequency of interactions of platelets with the endothelium, which is observed in animal models of diabetes, is caused by other factors. A primary cause may be a dysfunctional vascular wall.


The influence of health locus of control on the patient-provider relationship.
The physician-patient relationship is important to the successful delivery of health care. Health locus of control (HLOC) of the patient, the extent to which individuals attribute their health to their own actions or to external agents, may affect the patient-provider relationship. This study examined the influences of HIV and HLOC on trust in physician among a population of predominantly minority women and their family members. Powerful others HLOC demonstrated a positive relationship with trust in physician and chance HLOC had a negative relationship with trust in physician. HIV moderated both of these relationships.


Zerumbone augments cognitive enhancement potentials of EPA+DHA: insight from a hyperlipidaemic rat model.
Hyperlipidaemia and cognitive dysfunction (CD) are the two public health concerns. Though hyperlipidaemia has been comprehensively studied in respect to CVD, its role on CD needs to be explored. Hence, we evaluated hyperlipidaemia as a risk factor for CD and the efficacy of EPA (20 : 5n-3) + DHA (22 : 6n-3) and zerumbone (Z) in modulating CD under hyperlipidaemic conditions. Male Wistar rats (Rattus norvegicus) were fed control, high-fat (HF), high-fat + fish oil (HF + F), high-fat + zerumbone (HF+Z) and high-fat + fish oil + zerumbone (HF+F+Z) containing diets. After a 30 d feeding trial, memory parameters (Morris water maze, elevated plus maze (transfer latency) and T-maze (spontaneous alteration)) and locomotor skills (open field test and rotarod test) were assessed. Hyperlipidaemia significantly (P < 0·05) reduced memory and motor coordination skills compared with control. However, the administration of EPA + DHA and zerumbone significantly (P < 0·05) restored the hyperlipidaemia-induced loss of memory and motor coordination skills. Collectively, our data imply that hyperlipidaemia causes CD by decreasing memory and motor coordination skills, and administration of EPA + DHA and zerumbone prevents hyperlipidaemia-induced CD. The augmented effect of EPA + DHA, together with zerumbone, discloses a promising strategy for lowering the severity of CD in hyperlipidaemic conditions.


Cholinergic potentiation of the meal-related rise in ACTH and cortisol concentrations in men.
The present study examined the influence of physostigmine, an acetylcholine esterase inhibitor, on the secretory activity of the hypothalamo-pituitary-adrenocortical (HPA)--axis under basal (experiment I) and stimulated (experiment II) conditions in young healthy men. In a third experiment, the effect of scopolamine, a muscarinic acetylcholine receptor antagonist, on HPA secretory activity after physiological stimulation was tested. The experiments started between 09.00 and 10.00 a.m.. After a resting period of 1.5 h, either physostigmine (0.0125 mg per kg body weight soluted in isotonic saline) or placebo (saline) was infused within 15 min. In experiment I subjects (n = 7) remained fasting while in experiment II (n = 18) a standardized lunch was offered after the infusion. Experiment III (n = 7) was designed as experiment II but instead of physostigmine, scopolamine or placebo (0.5 mg) was subcutaneously injected 105 min before the meal. Blood for the determination of ACTH and cortisol was drawn in regular intervals during the experiments. Physostigmine did not change basal ACTH and cortisol secretion per se, excluding activation of basal HPA secretion due to acetylcholineesterase inhibition and its non specific side effects. Meal intake stimulated ACTH and cortisol secretion which was significantly enhanced when physostigmine was administered (p < 0.05). Scopolamine did not influence the meal related ACTH and cortisol secretion. These findings demonstrate that cholinergic neurotransmission is able to increase ACTH and cortisol concentrations in humans. This effect seems to be complementary to other stimulatory neurotransmitter systems, and is functional during stimulated HPA secretory activity and not under basal conditions.


A colorimetric aptasensor for sulfadimethoxine detection based on peroxidase-like activity of graphene/nickel@palladium hybrids.
A sensitive, rapid and label-free colorimetric aptasensor for sulfadimethoxine (SDM) detection was developed based on the tunable peroxidase-like activity of graphene/nickel@palladium nanoparticle (Gr/Ni@Pd) hybrids. The addition of the SDM aptamer could inhibit the peroxidase-like catalytic activity of the hybrids. However, the target SDM and aptamer could be triggered tightly and recover the catalytic activity of the Gr/Ni@Pd hybrids. Due to the peroxidase-like catalytic activity, Gr/Ni@Pd could catalyze the decomposition of H2O2 with releasing hydroxyl radicals which further oxidized reagent 3, 3', 5, 5'-Tetramethylbenzidine (TMB) to oxTMB accompanied with a colorless-to-blue color change. The original color change could be applied to obtain quantitative detection of SDM, due to the relationship between the concentration of the target and the color difference. As a result, this approach performed a linear response for SDM from 1 to 500 ng/mL with a limit detection of 0.7 ng/mL (S/N = 3) under the optimized conditions and realized the detection of SDM in spiked lake water samples. Therefore, this colorimetric aptasensor was an alternative assay for SDM detection in real water. Moreover, with its design principle, this work might be applied to detecting other small molecule by employing appropriate aptamer.


[A prospective study to assess the burden of influenza-related hospitalizations and emergency department visits among children in Bilbao, Spain (2010-2011)].
This study was undertaken to estimate the burden of morbidity associated with laboratory-confirmed influenza in children below 15 years of age. Children presenting with acute respiratory infection and/or isolated fever at the Basurto University Hospital, Bilbao, Spain between November 2010 and May 2011 were included in this study (NCT01592799). Two nasopharyngeal secretion samples were taken from each; one for a rapid influenza diagnostic test in the emergency department, and the second for laboratory analysis using real-time polymerase chain reaction and viral culture. A total of 501 children were recruited, of whom 91 were hospitalized. Influenza diagnosis was confirmed in 131 children (26.1%); 120 of 410 (29.3%) treated as outpatients and 11 of 91 (12.1%) hospitalized children. A total of 370 of 501 children (73.9%) had no laboratory test positive for influenza. The proportion of subjects with other respiratory viruses was 145/501 (28.9%) cases and co-infection with the influenza virus plus another respiratory virus was detected in 7/501 (1.4%) cases. Influenza virus types were: A (H1N1 and H3N2) 53.2% (67/126); B (Victoria and Yamagata) 46.0% (58/126); A+B 0.8% (1/126). The median direct medical costs associated with each case of laboratory-confirmed influenza was €177.00 (N=131). No significant differences were observed between the medical costs associated with influenza A and B. Almost half of the cases were influenza virus B type. The administration of a vaccine containing influenza A and B types to children below 15 years of age might reduce the overall burden of the illness.


Socio-economic disparities in tobacco consumption in rural India: evidence from a health and demographic surveillance system.
India houses over 275 million tobacco users, with 164 million users of only smokeless tobacco, 69 million exclusive smokers, and 42 million users of both smoking and smokeless tobacco. This study aims to examine the socio-economic factors associated with types of tobacco use in a selected rural Indian population. A cross-sectional study was conducted with surveillance data from the Birbhum Population Project (BIRPOP). Total respondents of 29,783 individuals (16,038 men and 13,745 women) aged ≥15 years were surveyed between October 2010 and January 2011. Apart from bivariate analyses, a binary logistic regression was applied to estimate the adjusted odds ratio for socio-economic factors (religion, social group, education, occupation, and wealth quintile) associated with current tobacco use, current smokeless tobacco use, and current bidi use among men and women. Nearly 22% of men and 26% of women were using smokeless tobacco. While 46% of men were smoking bidi, only 4% of women reported smoking bidi. Overall, men are more likely to use tobacco. Irrespective of gender, with increasing years of education, people are less inclined to use tobacco, and unemployed people are less likely to use tobacco. With increasing income, the odds of smokeless tobacco use and the odds of smoking bidi are higher among women and men, respectively. The BIRPOP study indicates that irrespective of gender and income, raising the level of awareness through household-based health education could be an effective intervention to minimise the level of tobacco use.


Sugar and alcohol stabilization of yeast in sweet wine.
Secondary fermentation of sweet wine was prevented by the Delle stabilization procedure. For this procedure, advantage is taken of the inhibitory effects of high concentrations of sugar as well as of alcohol. Thus, relatively small amounts of wine spirits were added to fermenting musts to obtain stability, as compared to the conventional procedure in which larger amounts of alcohol are added and the inhibitory effect of alcohol only is considered. The Delle value is a function of the concentrations in the wine, after spirits addition, of alcohol and sugar. Delle values which gave stable wine were dependent on time of alcohol addition, on strain of wine yeast, and on composition of wine spirits. Fractional addition of spirits, concentration of SO(2), and clarity of must had little effect on the Delle value. Sensory comparison of wines especially prepared for tasting by the Delle procedure and by the conventional procedure showed the wines made by the Delle procedure to be superior in quality. Under proper storage conditions, the Delle wines were shown to be microbiologically stable and resistant to wine spoilage organisms.


The role of game (wild boar and roe deer) in the spread of tick-borne encephalitis in the Czech Republic.
In the Czech Republic, the incidence of human tick-borne encephalitis (TBE) has been increasing over the last two decades. At the same time, populations of game have also shown an upward trend. In this country, the ungulate game is the main host group of hosts for Ixodes ricinus female ticks. This study examined the potential contribution of two most widespread game species (roe deer [Capreolus capreolus] and wild boar [Sus scrofa]) to the high incidence of TBE in the Czech Republic, using the annual numbers of culls as a proxy for the game population. This was an ecological study, with annual figures for geographical areas-municipalities with extended competence (MEC)-used as units of analysis. Between 2003 and 2011, a total of 6213 TBE cases were reported, and 1062,308 roe deer and 989,222 wild boars were culled; the culls of roe deer did not demonstrate a clear temporal trend, but wild boar culls almost doubled (from 77,269 to 143,378 per year). Statistical analyses revealed a positive association between TBE incidence rate and the relative number of culled wild boars. In multivariate analyses, a change in the numbers of culled wild boars between the 25th and 75th percentile was associated with TBE incidence rate ratio of 1.23 (95% confidence interval 1.07-1.41, p=0.003). By contrast, the association of TBE with culled roe deer was not statistically significant (p=0.481). The results suggest that the size of the wild boar population may have contributed to the current high levels and the rising trend in incidence of TBE, whereas the regulated population of roe deer does not seem to be implicated in recent geographical or temporal variations in TBE in the Czech Republic.


Antithyroid drugs and Graves' disease: a prospective randomized evaluation of the efficacy of treatment duration.
A prospective randomized study was performed in patients with hyperthyroid Graves' disease (GD) in order to compare long (18 months) and short term (6 months) antithyroid drug treatment on the remission rate. A therapeutic protocol was offered to all GD patients who had not been treated for this disease previously. All patients studied who followed the protocol were rechecked 2 yr after treatment was withdrawn, or earlier in the case of relapse. Of the patients having undergone long term treatment, 61.8% still were in remission 2 yr after treatment withdrawal, whereas only 41.7% of the patients treated for 6 months were in remission (P less than 0.05). Such findings clearly establish that treatment duration has a direct beneficial incidence on the remission rate. These results were confirmed by the fact that treatment for 18 months resulted in remission in 7 of 15 patients who had previously relapsed after a 6-month course of therapy. This improvement in relation to treatment duration might be due to the immunosuppressive action of carbimazole. No significant difference was observed between relapse and remission groups, regardless of treatment duration, for HLA ABDr, serum T3 and T4, and T3/T4 ratio determined before treatment. Only the thyroid-stimulating antibody levels determined at the time of diagnosis and at the end of treatment were higher in the relapse group, a difference that was relevant only globally, due to value scattering. Furthermore, thyroid-stimulating antibody levels at the end of treatment may indicate remission or, conversely, continuance of the pathological process.(ABSTRACT TRUNCATED AT 250 WORDS)


Pepsinogen Serology and Gastritis OLGA Staging in Mucosal Atrophy Assessment: A Cross-Sectional Study Involving East China Endoscopy Population.
The histological gastric stage (OLGA) plays an important role in evaluating gastric atrophy, a symptom which suggests a risk of gastric cancer (GC). However, gastroscopy is an invasive examination, which has limited application in populations undergoing physical examination. Serum pepsinogen (PG) and gastin-17 (G-17) levels are noninvasive indexes which are recommended when screening for GC. We aim to explore the correlation between PG/G-17 and OLGA stage, in order to provide reliable indexes for GC screening. The study included 453 asymptomatic individuals from East China undergoing physical examination, who then underwent endoscopy including collection of biopsy samples. Assays for serum PG, G-17, and Helicobacter pylori (Hp) were performed. Atrophy of gastric mucosa was graded according to OLGA for each individual. 453 participants, average age 52.46 ± 10.30 years, 253 male and 200 female, were included. In the asymptomatic physical examination population, serum PGI, PGII, and PGR levels decreased with increasing OLGA scores. PGI and PGR were inversely correlated with increasing OLGA stage in both Hp-positive and Hp-negative groups. The levels of serum PGI, PGII, and G-17 in the Hp-positive group were higher than those in the Hp-negative group; conversely, the PGR levels were lower. Furthermore, OLGA scores increased with age in the Hp-positive group. In conclusion, there is a significant correlation between OLGA stage and serum PG in populations from East China undergoing physical examination. Serum PG and G-17 combined with Hp test plays an important role in evaluating gastric atrophy.


The zinc finger protein Ynr046w is plurifunctional and a component of the eRF1 methyltransferase in yeast.
Protein release factor eRF1 in Saccharomyces cerevisiae, in complex with eRF3 and GTP, is methylated on a functionally crucial Gln residue by the S-adenosylmethionine-dependent methyltransferase Ydr140w. Here we show that eRF1 methylation, in addition to these previously characterized components, requires a 15-kDa zinc-binding protein, Ynr046w. Co-expression in Escherichia coli of Ynr046w and Ydr140w allows the latter to be recovered in soluble form rather than as inclusion bodies, and the two proteins co-purify on nickel-nitrilotriacetic acid chromatography when Ydr140w alone carries a His tag. The crystal structure of Ynr046w has been determined to 1.7 A resolution. It comprises a zinc-binding domain built from both the N- and C-terminal sequences and an inserted domain, absent from bacterial and archaeal orthologs of the protein, composed of three alpha-helices. The active methyltransferase is the heterodimer Ydr140w.Ynr046w, but when alone, both in solution and in crystals, Ynr046w appears to be a homodimer. The Ynr046w eRF1 methyltransferase subunit is shared by the tRNA methyltransferase Trm11p and probably by two other enzymes containing a Rossman fold.


One-to-one peer support in cancer care: a review of scholarship published between 2007 and 2014.
The primary goal of this review was to determine whether one-to-one peer support programmes benefit cancer patients. The secondary goal was to assess the quality of the research methodology and of the peer programme description as reported in original research studies. MEDLINE and PsycINFO databases were systematically searched in order to identify relevant studies published between May 2007 and July 2014. Eligible articles were evaluated using pre-existing criteria based on the Consolidated Standards of Reporting Trials Statement Checklist. This review included 13 studies: four randomised controlled trials, one non-randomised comparative study and eight one-group descriptive studies. All studies reported high participant satisfaction with the peer support intervention, and the majority noted positive outcomes regarding psychological adjustment. The quality of the description of the peer support programmes as well as the research methodology of the studies was rated as fair. Methodological weaknesses included biased recruitment strategies and limited information regarding peer volunteers, non-users of peer support and those who withdrew from support programmes. One-to-one peer support programmes have the unique advantage of being a low-cost intervention approach, but also showing potential for relieving the health-care system by reallocating some aspects of the cancer care to community settings. Future research should address the methodological weaknesses in study design and reporting.


Antipsychotics for the treatment of schizophrenia: likelihood to be helped or harmed, understanding proximal and distal benefits and risks.
Benefit-risk decisions are the central part of the philosophy of evidence-based medicine. Although number needed to treat (NNT) and number needed to harm (NNH) can quantify differences between two antipsychotics in terms of benefits and risks for the treatment of schizophrenia, these benefits and risks can take on greatly differing degrees of importance or relevance depending on the subjective point of view of the patient and clinician, baseline risks, severity of the underlying illness, as well as the time horizon when these effects emerge. The metric of likelihood to be helped or harmed, the ratio NNH to NNT, can be helpful in quantifying the benefit:risk ratio, provided that the outcomes are carefully matched in terms of both importance to the clinician and the patient and whether they are proximal or distal. The examples provided are extensions to the initially published NNT and NNH analyses conducted by the first author.


Expression of fibroblast growth factor receptor substrate 2 (FRS2) in primary retroperitoneal liposarcoma and its clinical implications.
The aim of this study was to investigate the expression level of fibroblast growth factor receptor substrate 2 (FRS2) in tissues of patients with primary retroperitoneal liposarcoma (PRPLS) and its correlation with recurrence and prognosis. The pathological specimens, medical records, and follow-up information of patients with PRPLS who underwent radical surgery for the first time in our hospital from January 2013 to December 2016 were retrospectively analyzed. FRS2 protein expression in tissues was determined by immunohistochemistry staining, and the FRS2 protein positive rates in patients with different clinicopathological features were compared. Factors influencing patients' recurrence and survival were determined using the multivariate Cox stepwise regression model. This research enrolled 87 patients with PRPLS, with the number of cases presenting FRS2 protein positive rate and positive rate in pathological tissues accounting for 62.07% (54/87) and 37.93% (33/87), respectively. The positive expression of FRS2 protein varied markedly among patients with different pathological types, FNCC, LCC grade, number of tumors, positive margin, and recurrence and metastasis (with vs. without) (all p<0.05). The 87 patients were followed up for 3.5-102 months (median, 27.5 months), with a postoperative 5-year overall disease-free survival (DFS) rate of 17.24% [median progression-free survival (PFS): 24.7 months] and a 5-year overall survival (OS) rate of 44.83% (median OS: 47.3 months). Kaplan-Meier survival curves revealed significantly shorter PFS and OS in patients with positive FRS2 protein expression vs. those with negative FRS2 protein expression (χ2=6.396, 5.032, p<0.05). According to the univariate analysis, the 5-year overall DFS rate varied significantly among patients with different pathological types, Fédération Nationale des Centres De Lutte Contre le Cancer (FNCLCC) grades, number of tumors, positive margin, and FRS2 protein expression (all p<0.05). Pathological type, FNCLCC grading, tumor number, recurrence and metastasis, positive margin, and FRS2 protein expression were significantly correlated with the 5-year OS rate of patients (all p<0.05). Furthermore, pathological type, FNCLCC grading, multiple tumors, positive margin, and FRS2 protein expression were identified by multivariate Cox regression analysis to be independent factors that affected patients' 5-year DFS and OS rates (all p<0.05), and that relapsed and metastasized patients had a 4.586-fold risk of death than those without recurrence and metastasis. FRS2 shows a high positive rate in the tissues of PRPLS patients and is significantly related to the prognostic recurrence and survival of patients, with potential value in judging the prognosis of patients.


Anion-Controlled Cation-Exchange Process: Intercalating α-Titanium Phosphate through Direct Ion Exchange with Alkylammonium Salts.
Several alkylammonium salts were used in the study of α-titanium phosphate (α-TiP) intercalation chemistry. The characterization results demonstrated that the expected intercalation by direct ion exchange could be successfully achieved without any addition of an extra amine substance. Our findings are different from the current opinion that by the ion-exchange method, without the assistance of bases, large cations are difficult to exchange into the narrow interlayer space of α-tetravalent metal phosphate directly because of the small interlayer distance. Studies found that alkylammonium cations, for example, n-butylammonium cation, could be directly exchanged into the interlayer space merely by choosing salts with appropriate anions such as phosphate, phosphite, sulfite, citrate, and malate ions. In the case of phosphates, besides n-butylammonium, the exchange of n-hexylammonium, cyclohexylammonium, and pyridinium with interlayer protons was investigated and successfully accomplished as well. The uptake values for these four cations were 0.420, 0.595, 0.571, and 0.335 g/g, respectively. A mechanism study revealed that although the relevant exchange reaction seemed only to involve the proton of α-TiP and the alkylammonium cation of the salt, the strength of the conjugate acid of the anion from the salt-the counterion-was proven to be the key factor in this process.


Beneficial effects of Angiotensin II receptor blockers in brain disorders.
A canonical brain Renin-Angiotensin System (RAS), like the canonical peripheral RAS, has long been proposed as a major regulator of brain function. Because of methodological limitations, however, this system is in urgent need of critical revision. The Angiotensin II AT1 receptors have been confirmed as key factors in the regulation of brain function, and AT1 receptor over activity has been established as a major and early injury factor in the development of many brain diseases. Consequently, Angiotensin Receptor Blockers (ARBs), compounds widely used to treat cardiovascular and metabolic disorders, are excellent candidates for repurposing for the treatment of brain disorders. This review will discuss some of the reasons why revisiting brain RAS is a pressing necessity, will present evidence for a participation of AT1 receptor over activity in the development of major brain disorders, and will present definite evidence of ARBs neuroprotective effects. The review will focus on the beneficial effects of ARB therapy in stroke, neurodegenerative disorders including Alzheimer's and Parkinson's diseases, traumatic brain injury, radiation- induced brain damage, stress and mood disorders.


Outbreak of foot and mouth disease and peste des petits ruminants in sheep flock imported for immediate slaughter in Riyadh.
To detect and identify the causative agent or agents of the following clinical symptoms which were fever, lack of appetite, salivation, vesiculation, erosions of the buccal mucosa, nose, and feet. The signs vary from mild to severe. The mortality rate of the disease is high. The morbidity rate reaches up to 100%. Sheep also show bloody diarrhea and rapid respiration. Sheep flock resident in El-Kharje Governorate. A total of 50 serum samples and 50 buffy coat samples were collected from Marino sheep flock suffered from high mortalities, fever, lameness, diarrhea, stomatitis, and respiratory distress. PrioCHECK® foot and mouth disease virus (FMDV) nonstructural (NS) (marketable enzyme-linked immunosorbent assay [ELISA] kit) was used for revealing of the NS antibodies and liquid phase blocking enzyme immunoassay (LPBE) for identifying the FMD serotype and examined by competitive ELISA (cELISA) for detection of peste des petits ruminants (PPR) antibodies. The buffy coat samples were examined by immunocapture ELISA (Ic ELISA) for detection of PPR antigen. Using PrioCHECK® FMDV NS: Commercial ELISA kit: 38/50 (76%) of the serum samples were positive for the presence of FMD NS viral proteins. In addition, using LPBE the positive samples were identified as FMD serotype O. Examination of the serum sample by cELISA for detection of PPR antibodies gave positive results in 32/50 (64%). While the Ic ELISA identified 32 (64%) positive reactors for PPR antigen. This study reflected high susceptibility of the imported sheep flocks to the infection with FMD and PPR viruses, which are endemic in the Kingdom of Saudi Arabia (KSA). Hence, the imported flocks that prepared for slaughter must be vaccinated with the used vaccine in KSA in the quarantine for the control of FMD especially when importation occurs from counters that are free from these diseases.


Randomized trial of laparoscopic cholecystectomy procedure-specific consent form.
Prior to all surgical procedures, possible risks are outlined to patients during an informed consent discussion, and they are invited to ask questions. Written consent records this discussion and signals a patient's willingness to proceed with surgery. This study aims to improve the documentation of complications discussed during laparoscopic cholecystectomy consent through the introduction of a procedure-specific consent form. Phase 1 included a retrospective analysis of possible complications documented on standard consent forms for laparoscopic cholecystectomy. Phase 2 was a prospective randomized comparison of existing standard consent forms versus procedure-specific consent forms measuring the documentation of significant complications as identified from the Royal Australasian College of Surgeons brochure for laparoscopic cholecystectomy. These include bile duct injury, bile leak, bleeding, infection, conversion and damage to other organs. The proportion of participants in each cohort with the documentation of specific complications was assessed using the two-sample test of differences in proportions. Phase 1 of the study found that the possible risk of bleeding was documented in 82.1% of cases, while damage to other organs was only documented in 7.7%. Phase 2 of the study showed significant improvements in the documentation of specific complications for both standard and procedure-specific consent cohorts; 76.5% of participants in the procedure-specific consent cohort had all complications documented, while no participants in the phase 1 cohort had all complications documented. Introduction of a procedure-specific consent form for laparoscopic cholecystectomy has improved the documentation of a standard set of complications.


Cooling and diffusion characteristics of a hot carrier in the monolayer WS2.
The characteristics of a hot carrier distributed in the C excitonic state of the monolayer WS2 is investigated by exploiting the transient absorption (TA) spectroscopy. The hot carrier cooling lifetime gradually prolongs from 0.58 ps to 2.68 ps with the absorbed photon flux owing to the hot phonon bottleneck effect, as the excitation photon energy is 2.03 eV. Meanwhile, the normalized TA spectra shows that the spectral feature of hot carriers is different from that of normal carriers. Based on the modified Lennard-Jones model, the average distance among hot carriers can be estimated according to the peak shift of TA spectra and the diffusion velocity can also be calculated simultaneously. The hot carrier limits the diffusion of the photo-generated carrier at the initial several picoseconds. These results help people to elucidate the hot carrier dynamics in 2D TMDCs and give guidance on the designing and optimizing the TMDC-based electronic devices of high performance.


Prostate development requires Sonic hedgehog expressed by the urogenital sinus epithelium.
The prostate gland develops from the urogenital sinus by a testosterone-dependent process of ductal morphogenesis. Sonic hedgehog (Shh) is expressed in the urogenital sinus epithelium and the time course of expression coincides with the formation of the main prostatic ducts. Expression is most abundant in the lumen of the urogenital sinus and in the contiguous proximal duct segments. The initial upregulation of Shh expression in the male urogenital sinus depends on the presence of testosterone. The function of Shh was examined in the male urogenital sinus which was transplanted under the renal capsule of an adult male host mouse. Blockade of Shh function by a neutralizing antibody interferes with Shh signaling and abrogates growth and ductal morphogenesis in the transplanted tissue. These observations show that testosterone-dependent Shh expression in the urogenital sinus is necessary for the initiation of prostate development.


Involvement of P2Y1, P2Y6, A1 and A2A Receptors in the Purinergic Inhibition of NMDA-Evoked Noradrenaline Release in the Rat Brain Cortex.
In the cerebral cortex, glutamate activates NMDA receptors (NMDARs), localized in noradrenergic neurons, inducing noradrenaline release that may have a permissive effect on glutamatergic transmission, and therefore, on the modulation of long-term plasticity. ATP is co-released with noradrenaline, and with its metabolites (ADP and adenosine) is involved in the purinergic modulation of electrically-evoked noradrenaline release. However, it is not known if noradrenaline release evoked by activation of NMDARs is also under purinergic modulation. The present study aimed to investigate and to characterize the purinergic modulation of noradrenaline release evoked by NMDARs. Stimulation of rat cortical slices with 30 µM NMDA increased noradrenaline release, which was inhibited by ATP upon metabolization into ADP and adenosine and by the selective agonists of A1 and A2A receptors, CPA and CGS2680, respectively. It was also inhibited by UTP and UDP, which are mainly released under pathophysiological situations. Characterization of the effects mediated by these compounds indicated the involvement of P2Y1, P2Y6, A1 and A2A receptors. It is concluded that, in the rat brain cortex, NMDA-evoked noradrenaline release is modulated by several purinergic receptors that may represent a relevant mechanism to regulate the permissive effect of noradrenaline on NMDA-induced neuroplasticity.


Effect of isoenzyme composition on Kodak Ektachem test results for creatine kinase, lactate dehydrogenase, alkaline phosphatase, and amylase.
Seventy-four patients' sera containing macroenzymes or other uncommon enzyme forms were analyzed for total creatine kinase, lactate dehydrogenase, alkaline phosphatase, or amylase activity on an Ektachem 700XR analyzer. The Ektachem test results correlated well with activities obtained by means of liquid reagents on RA-1000. For each enzyme tested, linear-regression analysis yielded data comparable with those for sera containing exclusively the more common isoenzymes. Increased concentrations of intestinal ALP, however, resulted in higher activities of total ALP being reported for the Ektachem.


Spectrum of Microorganisms, Antibiotic Resistance Pattern, and Treatment Outcomes Among Patients With Empyema Thoracis: A Descriptive Cross-Sectional Study From the Bahawal Victoria Hospital Bahawalpur, Punjab, Pakistan.
Background: This study involves the analysis of spectrum of microorganisms, antibiotic resistance pattern, and treatment outcomes among empyema thoracis patients. This study also analyzes the factors associated with unsuccessful treatment outcome and duration of hospital stay among the patients. Methods: This was a descriptive, cross-sectional study carried out in the Pulmonology Ward of the Bahawal Victoria hospital, Bahawalpur, Pakistan. All patients with empyema thoracis registered at the study site during the period of 1 year were included in the study. Multivariate regression analysis was used to analyze the factors associated with duration of hospital stay and unsuccessful treatment outcome among the patients. Results: A total 110 patients were included in the study. Most of the patients (n = 73, 66.4%) were treated with piperacillin/tazobactam alone and in combination with either one or more than one antibiotics as an empiric therapy. Culture was positive in 58 (52.7%) patients and the most commonly identified organisms included, gram-negative Pseudomonas aeruginosa (n = 20; 18.8%) and Klebsiella sp. (n = 11, 10%) followed by same proportion of E. coli. The most commonly identified bacterial isolates showed high level of resistance against antibiotics used as an empiric therapy, while these showed low level of resistance against amoxicillin, clarithromycin, ertapenem, colistin, tigecycline, fosfomycin, rifampicin, and vancomycin. In this study, 82 (74.5%) patients successfully completed the treatment, while 12 (11%) showed no clinical improvement, 5 (4.5%) lost to follow up and 11 (10%) died. In multivariate binary logistic regression analysis, none of the patient attributes were significantly associated with unsuccessful treatment outcome, while in multivariate linear regression analysis, the factors which were significantly associated with duration of hospital stay included; duration of symptoms <2 weeks prior to admission (p = 0.008, beta = -0.247) and resistance to five antibiotic classes (p = 0.02, beta = 0.280). Conclusion: Close to 25% of the patients did not complete the treatment successfully. Most of the common bacterial isolates showed high level of resistance against the broad-spectrum antibiotics used as an empiric therapy. This is alarming. However, better sensitivity of common bacterial isolates against standardized first line treatment for empyema thoracis is promising.


A cytogenetic study on workers exposed to low concentrations of benzene.
A cytogenetic study was performed on 22 healthy workers engaged in benzene production and exposed to low concentrations of benzene, ranging from 0.2 to 12.4 p.p.m. (threshold limit value 10 p.p.m.). Workers were divided into two groups according to the different levels of exposure, inferrable also from the concentration of benzene in the alveolar air and the levels of urinary phenols. Each exposed subject was paired with a suitable control, living in the same area and of similar smoking habits and age. No statistically significant increase of sister chromatid exchange (SCE) frequency was observed in the exposed groups. In controls, SCE frequency was positively correlated with age and smoking habits. Among structural chromosomal aberrations, only the chromosome-type ones were significantly higher in exposed than in control subjects, and their increase was still significant when gaps were discarded.


The Role of Histone Post-Translational Modifications in Merkel Cell Carcinoma.
Merkel Cell Carcinoma (MCC) is a rare but highly aggressive form of non-melanoma skin cancer whose 5-year survival rate is 63%. Merkel cell polyomavirus (MCPyV), a small DNA tumor virus, is the etiological agent of MCC. Although representing a small proportion of MCC cases, MCPyV-negative MCCs have also been identified. The role of epigenetic mechanisms, including histone post-translational modifications (PTMs) in MCC, have been only partially determined. This review aims to describe the most recent progress on PTMs and their regulative factors in the context of MCC onset/development, providing an overview of current findings on both MCC subtypes. An outline of current knowledge on the potential employment of PTMs and related factors as diagnostic and prognostic markers, as well as novel treatment strategies targeting the reversibility of PTMs for MCC therapy is provided. Recent research shows that PTMs are emerging as important epigenetic players involved in MCC onset/development, and therefore may show a potential clinical significance. Deeper and integrated knowledge of currently known PTM dysregulations is of paramount importance in order to understand the molecular basis of MCC and improve the diagnosis, prognosis, and therapeutic options for this deadly tumor.


Multiple myeloma and immunosecretory disorders: an update.
The immunosecretory disorders are a diverse group of diseases associated with proliferation of an abnormal clone of immunoglobulin (Ig)-synthesizing, terminally differentiated B cells. These disorders include multiple myeloma (MM) and its variants, plasmacytoma, Waldenstrom macroglobulinemia, monoclonal gammopathy of undetermined significance, and monoclonal Ig deposition diseases, the latter including primary amyloidosis and nonamyloidotic types. These disorders are histologically composed of plasma cells, or plasmacytoid cells which produce Ig that is synthesized and usually secreted and can be deposited in some diseases. The Ig can be complete or can be composed of either heavy or light chains and is termed M-(monoclonal) protein. In MM, this proliferation overwhelms the normal cellular counterparts that synthesize and secrete appropriate levels of Ig. Immunosecretory disorders have been classified in multiple schemes, mostly morphologic, to such a degree that the classification of these entities has become a challenge to pathologists. The World Health Organization classification in 2001 was helpful because it provided specific clinicopathologic criteria for diagnosis. However, terms such as "progressive" disease were not well defined. In 2003, the International Myeloma Group defined MM as a disease with related organ and tissue injury, serving to better explain progressive in terms of deterioration of organ (renal, bone, and bone marrow) function over time. Therefore, modern classification of immunosecretory diseases is based on integration of clinical, morphologic, laboratory, radiographic, and biologic (including molecular) parameters, which we review here.


Uptake of Vinca alkaloids into mammalian nerve and its subcellular components.
Three Vinca alkaloids, vinblastine (VLB), vincristine (VCR), and vindesine (VDS), were recently found to affect axoplasmic transport to different degrees, with VCR the most potent. The uptake of these three species by desheathed cat sciatic nerves in vitro was determined by using tritium-labeled derivatives. In a sucrose medium, the uptake of VCR was found to be three to four times greater than that of VLB and VDS, which is in accord with the neurotoxicity of VCR. Uptake of VCR was dependent on Ca2+ concentration in the medium. Removal of Ca2+ from the incubation medium reduced the uptake of VCR, without having much effect on VLB or VDS uptake. The uptake of all three Vinca agents into nerve in a saline medium was about 50% of that in a sucrose medium, and elimination of Ca2+ from the saline incubation medium did not result in any significant change in uptake. High Ca2+ concentrations (100 mM) in the incubation medium, which cause a block of axoplasmic transport, did not change the total uptake of the Vinca alkaloids to any significant degree. The amount of labeled alkaloid found in the soluble fraction was, however, decreased by 50%. There was an increase in the amount present in the particulate fraction, caused, most likely, by an aggregation of vinca-binding components. The amount of VCR associated with tubulin-containing components isolated by gel filtration of the soluble fraction increased twofold when the nerves were exposed to a high-Ca2+ medium, as might be expected of a microtubule disassembly. Exposure of the nerve to low temperatures (0 degrees-4 degrees C) for 90 min did not show any effect on the total uptake of Vinca alkaloids.


Positive and negative signaling through SLAM receptors regulate synapse organization and thresholds of cytolysis.
X-linked lymphoproliferative syndrome, characterized by fatal responses to Epstein-Barr virus infection, is caused by mutations affecting the adaptor SAP, which links SLAM family receptors to downstream signaling. Although cytotoxic defects in SAP-deficient T cells are documented, the mechanism remains unclear. We show that SAP-deficient murine CD8(+) T cells exhibited normal cytotoxicity against fibrosarcoma targets, yet had impaired adhesion to and killing of B cell and low-avidity T cell targets. SAP-deficient cytotoxic lymphocytes showed specific defects in immunological synapse organization with these targets, resulting in inefficient actin clearance. In the absence of SAP, signaling through the SLAM family members Ly108 and 2B4 resulted in increased recruitment of the SHP-1 phosphatase, associated with altered SHP-1 localization and decreased activation of Src kinases at the synapse. Hence, SAP and SLAM receptors regulate positive and negative signals required for organizing the T cell:B cell synapse and setting thresholds for cytotoxicity against distinct cellular targets.


[A Case of Ascending Colon Cancer Showing Marked Reduction of Ascites by Bevacizumab Combination Chemotherapy].
A 68-year-old woman presented to our hospital with abdominal fullness. Computed tomography(CT)revealed ascites and massive tumors in the abdominal cavity. She was diagnosed with ascending colon cancer with peritoneal dissemination and ovarian metastasis. After ileostomy, panitumumab plus mFOLFOX6 therapy was initiated, but it was discontinued due to adverse events. As the ascites rapidly increased, her chemotherapy was changed to bevacizumab(BV)plus FOLFIRI. BV combination therapy resulted in a dramatic decrease in ascites and improved her quality of life, whereas the therapy did not reduce the primary and metastatic lesions. Our case suggested that BV could decrease ascites by inhibiting vascular endothelial growth factor(VEGF)-induced vascular permeability.


Effects of safflower seed extract supplementation on oxidation and cardiovascular risk markers in healthy human volunteers.
We previously demonstrated that safflower seed extract (SSE) and its major antioxidant constituents, serotonin hydroxycinnamic acid amides, suppressed LDL oxidation in vitro, decreased plasma autoantibody titres to oxidized LDL and attenuated atherosclerotic lesion formation in apoE-deficient mice. In this report, we examined whether SSE, rich in serotonin derivatives, could affect markers of oxidative stress, inflammation and aortic stiffness in healthy human subjects. Twenty Japanese male volunteers were studied at baseline, after 2.1 g SSE supplementation daily (providing 290 mg serotonin derivatives/d) for 4 weeks, and after a 4-week washout period. Significant reductions in circulating oxidized LDL, autoantibody titres to malondialdehyde-modified LDL, the soluble form of vascular cell adhesion molecule-1 (sVCAM-1), and urinary 8-isoprostane were observed after a 4-week intervention. Although there were no statistically significant differences in blood pressure or brachial-ankle pulse wave velocity (baPWV), an index of arterial stiffness, baPWV was lower than baseline in eleven of twenty subjects and was accompanied by a reduction in blood pressure. Statistically significant negative correlations were observed between the extent of initial cardiovascular risk markers (autoantibody titres, 8-isoprostane, sVCAM-1 and baPWV) and the effect of intervention. This suggested that individuals with elevated oxidative stress, inflammation, and/or arterial stiffness may receive more benefit from SSE supplementation.


A Rare Case of Hernia Incarceration Under the Closed Port-Site Fascia After Robot-Assisted Laparoscopic Radical Cystectomy: Insights and Management Strategies.
Most cases of port-site hernia were due to inadequate fascial closure of the port site. We experienced a rare case of hernia incarceration under the closed port-site fascia despite adequate closure of the fascia after robot-assisted laparoscopic radical cystectomy. In this case, the small intestine was incarcerated between the transversus abdominis and oblique abdominal muscles from the 12-mm trocar site for the assistant. We inserted forceps to release the incarceration, and the fascia and peritoneum of the port site were closed using a trocar site closure device under laparoscopy. We considered that all-layer suturing, including peritoneum and inner and outer oblique fascia suturing, was necessary for port-site closure, especially in patients with obesity, because hernias can occur with fascial closure alone.


Enhanced Thermostability of Glucose Oxidase through Computer-Aided Molecular Design.
Glucose oxidase (GOD, EC.18.104.22.168) specifically catalyzes the reaction of β-d-glucose to gluconic acid and hydrogen peroxide in the presence of oxygen, which has become widely used in the food industry, gluconic acid production and the feed industry. However, the poor thermostability of the current commercial GOD is a key limiting factor preventing its widespread application. In the present study, amino acids closely related to the thermostability of glucose oxidase from Penicillium notatum were predicted with a computer-aided molecular simulation analysis, and mutant libraries were established following a saturation mutagenesis strategy. Two mutants with significantly improved thermostabilities, S100A and D408W, were subsequently obtained. Their protein denaturing temperatures were enhanced by about 4.4 °C and 1.2 °C, respectively, compared with the wild-type enzyme. Treated at 55 °C for 3 h, the residual activities of the mutants were greater than 72%, while that of the wild-type enzyme was only 20%. The half-lives of S100A and D408W were 5.13- and 4.41-fold greater, respectively, than that of the wild-type enzyme at the same temperature. This work provides novel and efficient approaches for enhancing the thermostability of GOD by reducing the protein free unfolding energy or increasing the interaction of amino acids with the coenzyme.


The Structure-Activity Relationship of Pterostilbene Against Candida albicans Biofilms.
Candida albicans biofilms contribute to invasive infections and dramatic drug resistance, and anti-biofilm agents are urgently needed in the clinic. Pterostilbene (PTE) is a natural plant product with potentials to be developed as an anti-biofilm agent. In this study, we evaluated the structure-activity relationship (SAR) of PTE analogues against C. albicans biofilms. XTT (Sodium 2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide inner salt) reduction assay was used to evaluate the activity of the analogues against C. albicans biofilms. Knowing that hyphal formation is essential for C. albicans biofilms, anti-hyphal assay was further carried out. By comparing a series of compounds tested in this study, we found that compounds with para-hydroxy (-OH) in partition A exhibited better activity than those with other substituents in the para position, and the double bond in partition B and meta-dimethoxy (-OCH₃) in partition C both contributed to the best activity. Consistent results were obtained by anti-hyphal assay. Collectively, para-hydroxy (-OH), double bond and meta-dimethoxy (-OCH₃) are all needed for the best activity of PTE against C. albicans biofilms.


[Restoration of erectile function by reconstructing cavernous nerves with small intestinal submucosa grafts].
To investigate the restoration of erectile function by reconstructing cavernous nerves (CN) with small intestinal submucosa (SIS) grafts. We prepared SIS grafts, established rat models and divided the models into a CN ablation, a sham-operation and an SIS graft group. The CNs at both sides were severed with 1 cm ablated in the first group, and 0.5 cm removed in the third, followed by reconstruction with the SIS grafts. Three months after surgery, the apomorphine test was performed to evaluate the erectile function, and then all the rats were sacrificed to detect the expression of nNOS in the penis. Penile erection was observed in 72.73% (8/11) of the rats for (1.07 +/- 0.89) times within 30 min in the SIS graft group, as compared with 0% (0/11) of the rats for (0.00 +/- 0.00) times in the CN ablation group (P < 0.01), and 90.91% (10/11) of the rats for (2.19 +/- 1.17) times in the sham-operation group (P < 0.01). The number of nNOS nerve fibers was significantly larger in the SIS graft than in the CN ablation group (70.36 +/- 10.09 versus 22.09 +/- 4.76, P < 0.01), but both were significantly smaller than that of the sham-operation group (90.81 +/- 5.69, P < 0.01). The SIS grafting technique contributes to the recanalization of the severed CN and restoration of erectile function in rats after surgical injury.


Ribonucleic acid metabolism in rat liver during long-term adaptation to malnutrition.
Ornithine decarboxylase (ODC) and nucleolar DNA-dependent RNA polymerase (RNA polymerase I) activities increased in the liver of young adult male rats fed a 6% casein diet (malnourished) for 1 week when compared with rats fed a 25% casein diet (control). ODC activity increased progressively and reached a peak after 3 weeks of malnutrition and then decreased to control values by 5 weeks. RNA polymerase I reached peak activity 1 week after malnutrition was imposed, decreasing thereafter to control values by 3 weeks. At 4 and 5 weeks, RNA polymerase I activity in malnourished animals was lower than control. Nucleoplasmic DNA-dependent RNA polymerase activity remained unchanged in the first 2 weeks of malnutrition and decreased thereafter to values significantly lower than control. The data confirm our previous observations of cyclical changes during prolonged malnutrition and suggests a process of "biochemical adaptation" to malnutrition in which the organism enhances essential metabolic processes to maintain cellular homeostasis to the detriment of less essential functions like systemic growth.


Recrystallization of highly-mismatched Be(x)Zn(1-x)O alloys: formation of a degenerate interface.
We investigate the effect of thermally induced phase transformations on a metastable oxide alloy film, a multiphase Be(x)Zn(1-x)O (BZO), grown on Al2O3(0001) substrate for annealing temperatures in the range of 600-950 °C. A pronounced structural transition is shown together with strain relaxation and atomic redistribution in the annealed films. Increasing annealing temperature initiates out-diffusion and segregation of Be and subsequent nucleation of nanoparticles at the surface, corresponding to a monotonic decrease in the lattice phonon energies and band gap energy of the films. Infrared reflectance simulations identify a highly conductive ZnO interface layer (thicknesses in the range of ≈ 10-29 nm for annealing temperatures ≥ 800 °C). The highly degenerate interface layers with temperature-independent carrier concentration and mobility significantly influence the electronic and optical properties of the BZO films. A parallel conduction model is employed to determine the carrier concentration and conductivity of the bulk and interface regions. The density-of-states-averaged effective mass of the conduction electrons for the interfaces is calculated to be in the range of 0.31 m0 and 0.67 m0. A conductivity as high as 1.4 × 10(3) S · cm(-1) is attained, corresponding to the carrier concentration n(Int) = 2.16 × 10(20) cm(-3) at the interface layers, and comparable to the highest conductivities achieved in highly doped ZnO. The origin of such a nanoscale degenerate interface layer is attributed to the counter-diffusion of Be and Zn, rendering a high accumulation of Zn interstitials and a giant reduction of charge-compensating defects. These observations provide a broad understanding of the thermodynamics and phase transformations in Be(x)Zn(1-x)O alloys for the application of highly conductive and transparent oxide-based devices and fabrication of their alloy nanostructures.


Low-dose dexamethasone affects osteoblast viability by inducing autophagy via intracellular ROS.
Glucocorticoids (GCs) are closely associated with the progression of GC‑induced osteoporosis (GIOP) by inhibiting osteoblast viability. However, endogenous GCs are important for bone development. In addition, previous studies have demonstrated that GCs could induce autophagy, a cytoprotective process that is protective against various stressors. In the present study, the aim is to explore whether osteoblasts exhibited dose‑dependent viability in the presence of GCs due to autophagy. hFOB 1.19 osteoblasts were treated with various doses of dexamethasone (DEX; 10‑8‑10‑4 M) for 0, 24, 48 and 72 h. The results revealed a biphasic effect of DEX on the viability of hFOB 1.19 cells; a high dose of DEX (≥10‑6 M) accelerated cell apoptosis, while a low dose of DEX (10‑8 M) increased cell viability. Furthermore, significantly increased autophagy was observed in the low dose DEX treatment group, as indicated by the expression of the autophagy‑associated proteins beclin 1 and microtubule‑associated protein light chain 3, and the detection of autophagosomes. Another finding was that DEX upregulated intracellular reactive oxygen species (ROS), which was decreased by the autophagy agonist rapamycin. The increase in autophagy and cell viability associated with low‑dose DEX (10‑8 M) was suppressed by the ROS scavenger catalase and the autophagy inhibitor 3‑methyladenine. In conclusion, the results revealed that GCs affected osteoblast viability in a dose‑dependent manner. A low dose of GCs increased osteoblast viability by inducing autophagy via intracellular ROS. The results indicate that autophagy may be a novel mechanism by which osteoblasts survive GC exposure and provide a potential therapeutic target for treating GIOP.


Tangier disease. In vitro conversion of proapo-A-ITangier to mature APO-A-ITangier.
Tangier disease is a disorder characterized by low levels of apo-A-I and high density lipoproteins. The defect in Tangier disease is an abnormal A-I apolipo protein, designated apo-A- ITangier . In normal subjects, apo-A-I is secreted as proapo -A-I with subsequent extracellular conversion to mature apo-A-I. The major form in normal plasma is mature apo-A-I with small amounts of proapo -A-I. In Tangier disease, proapo -A- ITangier is present in roughly equivalent concentrations compared to mature apo-A- ITangier . It has been proposed that the defect in Tangier disease is in the conversion of pro- to mature apo-A- ITangier . To test this, proapo -A-I was isolated from normal and Tangier subjects, and the conversion to the mature form by plasma from normal and Tangier subjects was analyzed. Incubation of radiolabeled normal proapo -A-I in normal plasma anticoagulated with heparin was associated with progressive conversion to mature apo-A-I over 24 h (initially 85% of the radioactivity was in the proapo -A-I isoform; at 24 h 33% radioactivity remained in the pro-isoform). Proapo -A- ITangier was also converted to the mature isoform during 24 h of incubation in normal plasma. Initially, 84% of radioactivity was in proapo -A- ITangier , and by 24 h the radioactivity in this isoprotein had decreased to 36%. A similar pattern of conversion was also observed when proapo -A- ITangier was incubated in Tangier plasma. The proteolytic conversion of both normal proapo -A-I and proapo -A- ITangier was unaffected by the serine protease inhibitors phenylmethylsulfonyl fluoride (1 mM) or aprotinin (200 Kallikrein-inactivating units/ml), but was inhibited by EDTA (0.1%). These results indicate that proapo -A- ITangier can be converted to mature apo-A- ITangier by the converting enzyme in normal plasma. In addition, plasma from a Tangier subject can convert both normal and Tangier proapo -A-I to the mature form. These results establish that proapo -A- ITangier can be rapidly converted to mature apo-A- ITangier , and there is no deficiency of the converting enzyme activity in Tangier disease.


[Axis divergence in electrocardiography as a sign of heart disease].
In the ecgs of 3433 patients the QRS- and T-vectors were determined. The borderline between physiological and pathological ranges of axis-divergence is found to show fluctuations. The younger the patient and the steeper the electrical heart axis, the greater is the physiological axis-divergence. Ignoring this fact many young people by mistake are taken to suffer from a cardiac disease on account of a great axis-divergence. On the other hand the same setting often is the only sign of a heart disease. The axis-divergence can be a useful factor for the computer-analyzed ecg, although the evaluation of a tenfold of ecgs seems to be necessary to achieve a statistically significant statement.


[Analysis on heavy metal concentrations in agricultural soils of Baoshan, Shanghai].
Based on the acquisition of heavy metal data from 216 topsoil samples of the agricultural land in Baoshan District, a typical region of Shanghai City, the content, distribution characteristics and sources of the heavy metals in agricultural soil of Shanghai Baoshan District were analyzed with the methods of combining multivariate statistics and geo-statistical. The results show that the average concentrations of the Cd, Hg, As, Cr, Pb, Cu and Zn in agricultural soil of Baoshan District are 0.195, 0.148, 7.44, 82.5, 29.1, 33.2 and 124.5 mg x kg(-1), they are lower than the secondary standards of the national soil environment; but the average concentrations of the Cd, Hg, Cr, Pb, Cu and Zn are more than background values of soil in Shanghai. Especially the Cd, Hg, Zn, they are 1.50, 1.48, 1.45 times higher than the background values, showing a net cumulative trend. The results of correlation analysis and factor analysis show that the sources of these elements can be divided into three categories; the Zn, Cd, Hg and Pb as one class; the Cr and Cu as another class; the As in a separate category. The concentrations of the former two classes are much higher than the background value, implying mainly from various human activities; the content of the As is almost the same as the background value of soil, it has the lowest degree of variation. Spatial structure analysis shows that the distribution of the As is influenced by the soil structural variations, such as soil parent material, topography, and other elements are mainly affected by random factors of human activities. Through the probability distribution of contour lines of the critical value, it can be found that the Cd, Zn, Cr, Cu, Hg come mainly from the point sources of pollution, but the source of Pb is relatively dispersed.


A cross-sectional multisite exploration of Italian paediatric nurses' reported burnout and its relationship to perceptions of clinical safety and adverse events using the RN4CAST@IT-Ped.
To explore Italian paediatric nurses' reported burnout and its relationship to their perceptions of safety and adverse events. A cross-sectional study using the RN4CAST@IT-Ped database with a web-based survey design. The RN4CAST@IT-Ped questionnaire was used to collect data in 2017. This comprised three main components: three dimensions (22 items) of the Maslach Burnout Inventory including emotional exhaustion, depersonalization and personal accomplishment. Participants also scored an overall grade of patient safety and estimated the occurrence of adverse clinical events. Nurses (N = 2,243) reported high levels of burnout. Most rated clinical safety as high. The risk of adverse events ranged from 1.3-12.4%. The degree of burnout appeared to influence the perception of safety and adverse events. The association between nurses' burnout and perceptions of higher rates of adverse events and reduced safety in clinical practice is an important finding. However, it is unclear whether this was influenced by a negative state of mind, and whether reduced safety and increased adverse events negatively influenced nurses' well-being, thus leading to burnout. Regardless, the association between nurses' burnout and these quality concepts needs further exploration to examine the effect, if any, on burnout and safety, and identify supportive mechanisms for nurses. The association between reported burnout and perception of safety and risk of adverse events in Italian paediatric nurses has been reported for the first time. Nurses reporting burnout are at greater risk of intensely negative perceptions of clinical safety and adverse events. This is an important finding as perceptions can influence practice and behaviours. Quality measures in children's clinical environments need to go beyond obvious indicators to examine nurses' well-being as this also influences quality and safety.


Formation of vacuum-formed and pressure-formed mouthguards.
The method used to form mouthguards should be carefully selected in order to obtain their full preventive benefits. The aim of this study was to examine the differences of mouthguard characteristics according to the forming methods. Mouthguard sheets of 3.8-mm ethylene vinyl acetate were vacuum-formed and pressure-formed on a working model. The sheets were formed when heating causing them to displace 15 mm from baseline. Mouthguard thickness was measured at the labial surface of the central incisor, the buccal surface of the first molar, and the occlusal surface of the first molar. The fit of the mouthguard was measured at the central incisor and the first molar. Differences in the thickness and fit between the vacuum-formed and pressure-formed mouthguards were analyzed by two-way analysis of variance and the Bonferroni method. Mouthguard thickness varied between the central incisors and first molars (P<.01). The thicknesses at the labial surface of the central incisor and the buccal surface of the first molar were greater in the vacuum-formed mouthguards than in the pressure-formed mouthguards (P<.01). The fit was better in the pressure-formed mouthguards than that in the vacuum-formed mouthguards (P<.01). The vacuum-forming method maintained the mouthguard thickness, while the pressure-forming method obtained better fit.


Spatial learning sculpts the dendritic arbor of adult-born hippocampal neurons.
Neurogenesis in the hippocampus is characterized by the birth of thousand of cells that generate neurons throughout life. The fate of these adult newborn neurons depends on life experiences. In particular, spatial learning promotes the survival and death of new neurons. Whether learning influences the development of the dendritic tree of the surviving neurons (a key parameter for synaptic integration and signal processing) is unknown. Here we show that learning accelerates the maturation of their dendritic trees and their integration into the hippocampal network. We demonstrate that these learning effects on dendritic arbors are homeostatically regulated, persist for several months, and are specific to neurons born during adulthood. Finally, we show that this dendritic shaping depends on the cognitive demand and relies on the activation of NMDA receptors. In the search for the structural changes underlying long-term memory, these findings lead to the conclusion that shaping neo-networks is important in forming spatial memories.


Measurement of tumor volume is not superior to diameter for prediction of lymph node metastasis in early gastric cancer with minute submucosal invasion.
The current indication for endoscopic resection in early gastric cancer (EGC) with minute (< 500 µm) submucosal invasion is based on tumor diameter, which may be insufficient to predict lymph node metastasis (LNM). We investigated whether tumor volume might more accurately predict LNM in EGC with minute submucosal invasion. Among patients who underwent gastrectomy for gastric cancer, 346 with well/moderately differentiated EGC with submucosal invasion <500 µm were evaluated. Three-dimensional tumor volume was calculated using an endoscopically resected specimen and compared with 1-dimensional tumor diameter. Predictive ability of tumor diameter or volume for LNM was evaluated using receiver operating characteristic curve analysis. Tumor diameter and volume predicted LNM with an area under the curve (AUC) of 0.567 and 0.589, respectively. AUC, sensitivity, specificity, positive and negative predictive values, and accuracy of the 2 models were not significantly different. Tumor diameter ≥ 3 cm showed a significant association with LNM (odds ratio [OR], 2.57; 95% confidence interval [CI], 1.01-6.57; P = 0.049), whereas a tumor volume cutoff value of 752.8 cm3 showed no significant association with LNM (OR, 1.52; 95% CI, 0.59-3.88; P = 0.385). Tumor volume had no advantage over diameter for predicting LNM in well/moderately differentiated EGC with minute submucosal invasion.


Stevens-Johnson syndrome and toxic epidermal necrolysis.
Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare, but potentially life threatening, diseases characterized by widespread epidermal necrosis, and are predominantly medication-induced. Unfortunately, though they are often associated with long-term debilitating sequelae, there are currently no efficacious pharmaceutical interventions proven through large clinical trials. It has been well established that the epidermal damage in these diseases is due to keratinocyte apoptosis. Although drug-specific T cells are implicated in this process, our understanding of the immunopathology is far from complete. The scenario suggested by today's literature points towards drug-specific CD8+ cytotoxic T cells utilizing perforin/granzyme B trigger keratinocyte apoptosis. Subsequently, there may be an expansion of apoptosis involving the interaction of either membrane-bound or soluble Fas ligand (sFasL) with its receptor Fas. The cellular source of sFasL remains controversial, with both peripheral lymphocytes and keratinocytes themselves as potential candidates. Cytokines produced by T lymphocytes, macrophages or keratinocytes may participate by activating keratinocytes and enhancing their expression of Fas and FasL, or by promoting the skin recruitment of lymphocytes by upregulating adhesion molecules. A better understanding of the underlying immunological mechanisms is required to identify appropriate therapeutic interventions. Finally, clinicians must remain vigilant about drug hypersensitivity to prevent SJS/TEN.


Indicators of fat distribution, serum lipids, and blood pressure in European women born in 1948--the European Fat Distribution Study.
In the spring of 1986, the authors studied the relation between body mass index and anthropometric indicators of fat distribution to cardiovascular risk factors (serum lipids and blood pressure) in approximately 450 women aged 38 years randomly selected from population registers in five European centers. Waist circumference was, in univariate analysis, more strongly related to triglycerides (positive association) and high density lipoprotein (HDL) cholesterol (negative association) than to body mass index or any other anthropometric measurement. Among the centers, we observed considerable variation in the strength of the associations between anthropometric measurements and risk factors. After adjustment for body mass index, most associations between skinfolds and circumferences and risk factors were reduced to statistically nonsignificant levels, but in some centers there were independent contributions of circumferences or circumference ratios to serum lipids, but not to blood pressures. Adjustment for differences in body mass index and fat distribution between the centers did not reduce the differences in cardiovascular risk factors between the different centers but instead revealed that serum cholesterol levels were lowest in the centers of southern Europe (Italy) and that HDL cholesterol levels were higher. Blood pressure was highest in the Swedish women. We conclude that in some female populations, but not in others, indicators of fat distribution are related to serum lipids but not to blood pressure, independent of body mass index.


Experimental investigation of a Brownian ratchet effect in ferrofluids.
We test experimentally a Brownian ratchet system suggested by Engel [Phys. Rev. Lett. 91, 060602 (2003)]. This ratchet system is based on a magnetic fluid that contains nanometer sized magnetic particles in a thermal bath of carrier fluid. An external static magnetic field and, perpendicular to it, an oscillatory magnetic field act on the ferrofluid particles; the total magnetic field contains no rotating component. The directed effective rotation of the particles due to the ratchet effect induces a macroscopic torque density of the fluid. The torque on a spherical ferrofluid sample is measured in dependence on the field parameters. A quantitative comparison with predictions from a microscopic and a phenomenological model are given. Both models describe certain aspects of the measurements correctly, but qualitative discrepancies between both models and experiment are found, particularly in the high-frequency range.


Relationships among performance, residual feed intake, and temperament assessed in growing beef heifers and subsequently as 3-year-old, lactating beef cows.
Seventy-four beef heifers were used to evaluate relationships among performance, residual feed intake (RFI), and temperament measured as growing heifers (Phase 1) and subsequently as 3-yr-old lactating beef cows (Phase 2) in the same cohort. In both phases, females were housed in a covered facility and fed similar forage-based diets, and individual feed intakes, BW, BCS, chute scores (CS), exit velocities (EV), and pen scores (PS) were collected throughout the 70-d feeding trials. In Phase 2, cows were milked on trial d 14 (lactation d 28 ± 3.5) and trial d 70 (lactation d 84 ± 3.5) to determine energy-corrected milk (ECM) production. Ultrasonic backfat thickness (BF), and ribeye area (REA) were evaluated on d 0 and 70 of the trial in Phase 2. Heifers were ranked by RFI and placed into Low (<0.5 SD mean RFI; n = 27), Medium (within ± 0.5 SD; n = 23), and High (>0.5 SD mean RFI; n = 24) RFI groups. Body weight, BCS, and ADG were similar among all RFI groups; however, daily DMI differed for all groups (P < 0.01) and was greater (10.76 ± 0.24 kg/d) for High, intermediate (9.88 ± 0.25 kg/d) for Medium, and less (8.52 ± 0.23 kg/d) for Low RFI heifers. When cow performance was analyzed based on RFI rank as heifers, BW, BCS, ADG, RFI, d 14 and d 70 ECM, BF, and REA were similar among RFI groups; however, cows that were most efficient as heifers (Low) had decreased (P < 0.05) daily DMI values (10.30 ± 0.41 kg/d) compared with cows that ranked Medium (11.60 ± 0.44 kg/d) or High (11.50 ± 0.43 kg/d) as heifers. The Pearson rank correlation between Phase 1 and 2 RFI was r = 0.13 (P = 0.30), and Pearson rank correlations showed no relationship (P > 0.1) between RFI and temperament. Phase 1 CS was negatively associated with ADG in Phase 1 (r = -0.28; P = 0.02) and 2 (r = -0.32; P = 0.01), and positively associated with d 14 (r = 0.24; P = 0.04) and 70 (r = 0.25; P = 0.03) ECM. Phase 2 CS was negatively associated with Phase 2 ADG (r = -0.29; P = 0.01) and positively associated with d 14 (r = 0.46; P = 0.001) and 70 (r = 0.33; P = 0.004) ECM. Phase 2 PS also tended to be negatively associated with DMI in Phase 1 (r = -0.20; P = 0.096) and 2 (r = -0.20; P = 0.08). In this study, heifers that were most feed efficient subsequently consumed less feed as lactating cows and maintained similar performance. Feed efficiency was not associated with differences in temperament; however, more excitable females had poorer BW gains and tended to have reduced feed intakes but produced more ECM.


Outcome of primary total hip arthroplasty in Charnley Class C patients with juvenile idiopathic arthritis: a case series.
The outcome and complications of 37 primary total hip arthroplasties by one surgeon in 24 patients with Charnley Class C juvenile idiopathic arthritis with up to 19.6 years follow-up are reported. Twenty-six femoral components were cementless; all acetabular components were cementless with screws. Age at operation averaged 22.6 years. Two patients (3 hips) have died. Twelve hips in 9 patients have failed. Six cementless acetabular components with conventional polyethylene were revised because of osteolysis after 5.5 to 14.5 years. All 3 cementless C2 femoral stems with minimal porous coating failed. One of eight cemented AML Bantam stems loosened at 3.5 years; 2 of 23 cementless AML Bantam stems loosened at 9.5 and 19.6 years. Pain relief and functional improvement are dramatic after total hip arthroplasty in juvenile idiopathic arthritis; however, the long-term outcome is guarded.


Planned Retirement Timing in Europe: Are Europeans Adapting to the Policy of Extending Working Lives.
As populations are ageing concerns regarding the sustainability of European welfare states have come to the forefront. In reaction, policy makers have implemented measurements aimed at the prolongation of working lives. This study investigates weather older workers have adapted their planned retirement age, as a result of this new policy credo. Based on data from Survey of Health, Ageing and Retirement in Europe (SHARE) the analysis shows an increase of the planned retirement age (1.36 years) across all ten European countries investigated, albeit with country-specific variations. Variations on the individual level can be detected in regard to gender, education and self-reported health status.


Molecular Mechanism of Dayuan Decoction in the Treatment of Fever Based on Network Pharmacology.
To study the molecular targets and mechanisms of Dayuan Decoction in the treatment of fever. The traditional Chinese medicine system pharmacological database and analysis platform (TCMSP) was used to search for the main active components and action targets of Dayuan Decoction. The GeneCards database was used to retrieve fever-related gene targets. The common gene targets were obtained by selecting the intersection of the action targets of the main active components of Dayuan Decoction and the fever-related gene targets using a Wayne diagram. Cytoscape 3.7.2 software was used to construct the drug active component action target network diagram. The protein-protein interaction PPI network of coacting targets was constructed using the STRING database. David data were used for Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses of common gene targets. A total of 89 main active components and 832 acting gene targets of Dayuan Decoction were screened, of which 50 were common gene targets of Dayuan Decoction and fever, including apoptosis regulatory factor Bel (BCL2L1), interleukin 6 (IL-6), interleukin 10 (IL-10), and tumor necrosis protein 53 (TP53). A total of 47 GO and 59 KEGG enrichment entries were obtained using GO and KEGG enrichment analyses, involving the cancer pathway, hypoxia-inducible factor 1 (HIF-1) signaling pathway, and mitogen-activated protein kinase (MAPK) signaling pathway. Dayuan Decoction has multitarget regulation characteristics and a multifaceted role in the treatment of fever.


Determination and impact of volatile organics emitted during rush hours in the ambient air around gasoline stations.
This study analyzes the volatile organic compounds (VOCs) in the ambient air around gasoline stations during rush hours and assesses their impact on human health. Results from this study clearly indicate that methyl tertiary butyl ether (MTBE), toluene, and isobutane are the major VOCs emitted from gasoline stations. Moreover, the concentrations of MTBE and toluene in the ambient air near gasoline stations are remarkably higher than those sampled on surrounding roads, revealing that these compounds are mainly released from gasoline stations. The concentration of VOCs near the gasoline stations without vapor recovery systems are approximately 7.3 times higher than those around the gasoline stations having the recovery systems. An impact on individual health and air quality because of gasoline station emissions was done using Integrated Risk Information System and Industrial Source Complex Short Term model.


Revision of the Oriental species of Calleida Latreille (sensu lato). Part 1: Introduction, groups of species, and species of six species groups (Coleoptera: Carabidae: Lebiini).
This revision focuses on the genus Calleida Latreille, 1824 (in the widest sense) in the Oriental Region, previously treated as genus or subgenus Callidiola Jeannel, 1949. In the present contribution, as first part of a series of revisions of the Asiatic Calleida species, we define nine species groups including all known Asiatic species, based on external features and morphological characters of male and female genitalia. A key for the identification of all nine species groups is provided, along with diagnostic characters, included species, geographical distribution, and brief discussion on monophyly and relationships for each species group. In particular, the present contribution deals with species of six small species groups, including eleven species in total, for which keys to all known species, descriptions, distribution maps, habitus images and genitalia illustrations are provided.Five new species are described: Calleida gressittiana Casale Shi, sp. n. (type locality: Kinabalu, Sabah, Borneo), Calleida puncticollis Shi Casale, sp. n. (type locality: Zigui, Hubei), Calleida jelineki Casale Shi, sp. n. (type locality: Coimbatore, India), Calleida viet Casale Shi, sp. n. (type locality: Vung Tau, Vietnam), Calleida borneensis Shi Casale, sp. n. (type locality: Sabah, Borneo). Lectotypes for five taxa are designated. One synonymy is newly proposed: Calleida lieftincki Louwerens junior synonym of Calleida corporaali Andrewes, syn. nov.


Safety of Treatments for ADHD in Adults: Pairwise and Network Meta-Analyses.
The aim of the study was to analyze evidence comparing the profile of drugs used to treat ADHD in adult patients. Systematic searches were conducted in electronic databases. Randomized, double-blind, parallel controlled trials that evaluated the safety of drugs in ADHD were included. The statistical analyses were conducted by pairwise meta-analyses and mixed treatment comparison (MTC). Ten ( n = 3006) trials were included in the analyses. We observed statistical differences for the following outcomes: decreased appetite between atomoxetine and placebo (odds ratio [OR] = 0.15, 95% credibility interval [CrI] = [0.05, 0.38]) and extended-release mixed amphetamine salts and placebo (OR = 0.06, 95% CrI = [0.00, 0.51]); insomnia between atomoxetine and placebo (OR = 0.48, 95% CrI = [0.27, 0.88]) and extended-release mixed amphetamine salts and placebo (OR = 0.23, 95% CrI = [0.06, 0.76]); sleepiness between atomoxetine and methylphenidate OROS (OR = 0.24, 95% CrI = [0.06, 0.97]); and decreased libido between atomoxetine and placebo (OR = 0.28, 95% CrI = [0.08, 0.90]). It was possible to generate evidence about the safety profile of different ADHD drugs.


Nerve and muscle involvement in mitochondrial disorders: an electrophysiological study.
Involvement of the peripheral nervous system in mitochondrial disorders (MD) has been previously reported. However, the exact prevalence of peripheral neuropathy and/or myopathy in MD is still unclear. In order to evaluate the prevalence of neuropathy and myopathy in MD, we performed sensory and motor nerve conduction studies (NCS) and concentric needle electromyography (EMG) in 44 unselected MD patients. NCS were abnormal in 36.4% of cases, and were consistent with a sensori-motor axonal multineuropathy (multifocal neuropathy), mainly affecting the lower limbs. EMG evidence of myopathy was present in 54.5% of patients, again mainly affecting the lower limbs. Nerve and muscle involvement was frequently subclinical. Peripheral nerve and muscle involvement is common in MD patients. Our study supports the variability of the clinical expression of MD. Further studies are needed to better understand the molecular basis underlying the phenotypic variability among MD patients.


Protective effect of amdinocillin against emergence of resistance to ceftazidime in Enterobacter cloacae.
Enterobacter cloacae infections have been shown clinically to respond less reliably to monotherapy with broad-spectrum cephalosporins than was initially expected. Selection of populations producing high levels of beta-lactamase has been shown to be the most frequent reason for treatment failure, and the use of these agents with another active antibiotic is recommended. In this study, E. cloacae strains from clinical specimens susceptible to ceftazidime and amdinocillin by broth dilution and disk tests were examined. In the presence of ceftazidime at 10 micrograms/ml, in vitro selection of resistant organisms was demonstrated for 3 of 11 strains. Selection was prevented when amdinocillin was added in combination. A more rapid killing was also demonstrated with this combination. At inocula of 10(8) CFU/ml, ceftazidime-resistant populations were isolated from 6 of 11 strains in vitro, and the emergence of this resistance was prevented by amdinocillin. The enhanced killing effect noted for amdinocillin with ceftazidime may have resulted in part from complementary activity of the antibiotics on penicillin-binding proteins. The ceftazidime-amdinocillin combination offers an interesting prospect for the therapy of infections caused by E. cloacae strains which are initially susceptible to both antibiotics.


Repeated administration of phencyclidine, amphetamine and MK-801 selectively impairs spatial learning in mice: a possible model of psychotomimetic drug-induced cognitive deficits.
Cognitive deficits are a key feature of schizophrenia. N-Methyl-D-aspartate (NMDA) receptor antagonists and amphetamine are known to induce psychotic behaviors and cognitive deficits in animals and humans, often affecting visuo-spatial abilities. Phencyclidine (PCP), MK-801 and amphetamine (AMPH) have been used in pharmacological animal models of schizophrenia, but none of these models has focused so far on spatial learning after repeated administration of the drugs. The objective of this study was to test whether repeated administration of PCP, AMPH or MK-801 influenced the performance of mice in a non-associative spatial learning test. CD-1 male mice were given i.p. daily injections of either saline, PCP (5.0, 10.0 mg/kg), AMPH (2.5, 5 mg/kg) or MK-801 (0.3, 0.6 mg/kg), for 5 days. On day 6 all mice were tested in an open field containing five different objects. After three sessions of habituation, each animal's reactivity to object displacement and object substitution was assessed. No significant differences among treatment groups were observed in object exploration or locomotion during the habituation phase. Five days of repeated PCP, AMPH or MK-801 administration selectively and differentially impaired the ability of mice to discriminate a spatial change, while leaving intact the ability to react to a non-spatial change. These data suggest that neurobiological adaptations to drug regimens known to induce psychotic behaviors and alterations in locomotor activity or stereotypies can also alter spatial learning, as assessed in this test, thus indicating that these regimens could also mimic some of the cognitive deficits observed in schizophrenia.


The visual ecology of a deep-sea fish, the escolar Lepidocybium flavobrunneum (Smith, 1843).
Escolar (Lepidocybium flavobrunneum, family Gempylidae) are large and darkly coloured deep-sea predatory fish found in the cold depths (more than 200 m) during the day and in warm surface waters at night. They have large eyes and an overall low density of retinal ganglion cells that endow them with a very high optical sensitivity. Escolar have banked retinae comprising six to eight layers of rods to increase the optical path length for maximal absorption of the incoming light. Their retinae possess two main areae of higher ganglion cell density, one in the ventral retina viewing the dorsal world above (with a moderate acuity of 4.6 cycles deg(-1)), and the second in the temporal retina viewing the frontal world ahead. Electrophysiological recordings of the flicker fusion frequency (FFF) in isolated retinas indicate that escolar have slow vision, with maximal FFF at the highest light levels and temperatures (around 9 Hz at 23°C) which fall to 1-2 Hz in dim light or cooler temperatures. Our results suggest that escolar are slowly moving sit-and-wait predators. In dim, warm surface waters at night, their slow vision, moderate dorsal resolution and highly sensitive eyes may allow them to surprise prey from below that are silhouetted in the downwelling light.


[Familial vesico-ureteral reflux and familial urinary tract infection (author's transl)].
In 6 families several members had vesico-ureteral reflux and/or recurrent urinary tract infections. From the analysis of the case reports the following tentative conclusions could be drawn: Familial reflux may be caused. 1. by primary insufficiency of the vesico-ureteral junction. 2. possibly by secondary changes consequent to a familial tendency to recurrent urinary tract infections.


[Optic neuropathy caused by amiodarone].
Amiodarone has been used for the last 20 years, initially as antianginal and then as antiarrhythmic agent. To the collateral effects described, the optic neuropathy must be added as a complication, not so frequent, caused apparently by the prolonged ingestion of it. Two patients treated with MDD of 250 mg of amiodarone, for a mean of 17 months, are reported. They presented a decrease of the visual acuity. After proposing the possible differential diagnosis, the relation between the use of amiodarone and the optic alteration observed is briefly exposed, relating it with the demyelination neuropathy induced by this drug. This presumption is corroborated by the ultrastructural alterations registered in the optic nerve of animals in which amiodarone was used, similar to those of the peripheral nerves, as an expression of a disorder of the lipidic metabolism, which allow it to be integrated to the so called iatrogenic lipidoses.


Autoantibodies to intrinsic factor can jeopardize pernicious anemia diagnosis: a case report.
Vitamin B12 deficiency may cause neurological and hematological alterations. Its assessment should be easy considering that the access to its measurement is available in majority of the clinical laboratories. The presence of technical interference when measuring vitamin B12 can lead to an erroneous or a more difficult diagnosis of conditions as pernicious anemia. We report a case in which an interference in the evaluation of vitamin B12 concentration led to the realization of invasive tests and almost a misdiagnosis of a patient who actually had pernicious anemia. Professionals need to be aware of these interferences when we assess outcomes.


Enoxaparin induced reactive thrombocytosis: a rare adverse drug reaction.
Objectives Enoxaparin is a low molecular weight heparin (LMWH), which belongs to the class of anticoagulants. The drug is administered as subcutaneous injection to prevent or treat deep vein thrombosis (DVT), pulmonary embolism and ischemic complications. Case Presentation A 57-year-old women diagnosed with acute coronary syndrome developed reactive thrombocytosis following the administration of enoxaparin subcutaneously. The blood test reports of the patient showed that there is a gradual elevation of platelet count day by day following enoxaparin administration. On an assessment using both World Health Organization-Uppsala Monitoring Centre (WHO-UMC) scale and Naranjo Causality Assessment Scale indicated that enoxaparin is the "probable" cause for the reaction. Conclusions We conclude that reactive thrombocytosis is a probable adverse drug reaction and close monitoring of blood counts is essential, following enoxaparin injection. More studies are to be conducted to identify further complications.


Zirconium(IV)-Benzene Phosphonate Coordination Polymers: Lanthanide and Actinide Extraction and Thermal Properties.
Coordination polymers with different P/(Zr + P) molar ratios were prepared by combining aqueous solutions of Zr(IV) and benzenephosphonate derivatives. 1,3,5-Benzenetrisphosphonic acid (BTP) as well as phosphonocarboxylate derivatives in which carboxylate substitutes one or two of the phosphonate groups were chosen as the building blocks. The precipitates obtained on combining the two solutions were not X-ray amorphous but rather were indicative of poorly ordered materials. Hydrothermal treatment did not alter the structure of the materials produced but did result in improved crystalline order. The use of HF as a mineralizing agent during hydrothermal synthesis resulted in the crystallization of at least three relatively crystalline phases whose structure could not be determined owing to the complexity of the diffraction patterns. Gauging from the similarity of the diffraction patterns of all the phases, the poorly ordered precipitates and crystalline materials appeared to have similar underlying structures. The BTP-based zirconium phosphonates all showed a higher selectivity for lanthanides and thorium compared with cations such as Cs(+), Sr(2+), and Co(2+). Substitution of phosphonate groups by carboxylate groups did little to alter the pattern of selectivity implying that selectivity in the system was entirely determined by the -POH group with little influence from the -COOH groups. Samples with the highest phosphorus content showed the highest extraction efficiencies for lanthanide elements, especially the heavy lanthanides such as Dy(3+) and Ho(3+) with separation factors of around four with respect to La(3+). In highly acid solutions (4 M HNO3) there was a pronounced variation in extraction efficiency across the lanthanide series. In situ, nonambient diffraction was performed on ZrBTP-0.8 loaded with Th, Ce, and a complex mixture of lanthanides. In all cases the crystalline Zr2P2O7 pyrophosphate phase was formed at ∼800 °C demonstrating the versatility of this structure.


Clostridium difficile Infections in Children: Impact of the Diagnostic Method on Infection Rates.
BACKGROUND Polymerase chain reaction (PCR) assays based on the detection of the toxin B gene are replacing enzyme-linked immunosorbent assay (ELISA)-based toxin production detection or cell cytotoxicity assay in most laboratories. OBJECTIVE To determine the proportion of pediatric patients diagnosed with Clostridium difficile infection by PCR who would have also been diagnosed by ELISA and to compare the clinical characteristics of PCR+/ELISA+ vs PCR+/ELISA- patients. METHODS Using the microbiology laboratory information system, stool samples positive for C. difficile by PCR between October 2010 and July 2014 were identified. Using frozen stool specimens, an ELISA for toxin A and B was performed. A retrospective medical chart review was conducted to obtain demographic and clinical data. Duplicate samples were excluded. RESULTS A total of 136 PCR-positive samples underwent ELISA testing: 54 (40%) were positive for toxin A or B. The mean (SD) age of the entire cohort was 8.5 (6.2) years. There was no difference in age, gender, clinical manifestation, previous medical problems, and management between patients positive or negative by ELISA. However, patients positive by ELISA were more likely to have had a recent exposure to antibiotics (67.9% vs 50%; crude odds ratio, 2.1 [95% CI, 1.03-4.28]). CONCLUSION In our pediatric population, 60% of patients with C. difficile diagnosed by PCR had no toxin detectable by ELISA. ELISA-negative patients were less likely to have received an antibiotic recently compared with ELISA-positive patients. These results highlight the need to standardize laboratory criteria for the diagnosis of C. difficile infections in children. Infect Control Hosp Epidemiol 2016;37:1087-1093.


New class of verdoheme analogues with weakly coordinating anions: the structure of (mu-oxo)bis[(octaethyloxoporphinato)iron(III)] hexafluorophosphate.
Three new verdoheme analogues with weakly coordinating anions, [OEOPFe(II)X], where OEOP is the monoanion of octaethyloxoporphyrin and X = PF(6), ClO(4), and BF(4), have been synthesized and characterized by spectroscopic methods. (1)H NMR spectroscopy reveals that the [OEOPFe(II)X] species are paramagnetic, and the iron is five-coordinate (S = 2). The oxidation of [OEOPFe(II)PF(6)] with dioxygen yields [(OEOPFe)(2)O](PF(6))(2). The structure of (mu-oxo)bis[(octaethyloxoporphinato)iron(III)] has been determined by X-ray diffraction analysis. The eight Fe-N bond distances have an average value of 2.077(3) Angstroms. The oxygen atom sits on the inversion center, and the average axial Fe-O bond length is 1.756(3) Angstroms. The average displacement of the iron(III) atom from the mean porphinato core is 0.60 Angstroms. Crystal data: crystal system, monoclinic; a = 8.7114(10) Angstroms; b = 26.102(4) Angstroms; c = 15.8323(14) Angstroms; beta = 104.134(6) degrees ; space group P2(1)/c; V = 3491.1(7) Angstroms (3); Z = 2; R1 = 0.0546, wR2 =0.1145 for data with I > 2sigma(I).


Core-shell-corona au-micelle composites with a tunable smart hybrid shell.
Micelles having a core of polystyrene and a mixed shell of poly(ethylene glycol) and poly(4-vinylpyridine) were formed through self-assembly of a triblock copolymer poly(ethylene glycol)- block-polystyrene- block-poly(4-vinylpyridine) in acidic water (pH 2). Reducing the HAuCl(4)-treated micelle solution leads to the formation of the Au-micelle composites with a core of polystyrene, a hybrid shell of poly(4-vinylpyridine)/Au/poly(ethylene glycol), and a corona of poly(ethylene glycol). The gold nanoparticles with controlled sizes were anchored to poly(4-vinylpyridine) to form the physically cross-linked hybrid shell. In aqueous solution, the hybrid shell is swollen and the swollen degree is sensitive to the pH condition. Under basic conditions, the channel in the hybrid shells of the composite is produced, which renders the composites a good catalytic activity. In addition, the composites also show good stability, unchanged hydrodynamic diameter, and surface plasmon absorption under different pH conditions.