Fe3O4-carboxyl modified AuNPs-chitosan@AgNPs as a robust surface-enhanced Raman scattering substrate for rapid analysis of tryptamine and ofloxacin in aquatic products.
Rapid and accurate quantification of trace targets in complex samples is an extremely challenging issue in fast analysis field. Herein, we developed Fe3O4-carboxyl modified AuNPs-chitosan@AgNPs composite (Fe3O4-AuNCs-Cs@AgNPs) as a robust surface-enhanced Raman scattering (SERS) substrate for rapid analysis of tryptamine (TPA) and ofloxacin (OFX). The substrate possessed abundant surficial active sites of -NH2, -OH and -COOH groups. The substrate exhibited good SERS activity for several different model molecules with enhancement factors (EFs) of 1.2 × 108 for 4-mercaptobenzoic acid. The substrate presented good stability for detection of TPA at pH 6.0 and OFX at pH 8.0, and relative standard deviations less than 5.0% for intra-batch and 6.0% for inter-batch. Also, the substrate possessed good time-stability within 50 days. The substrate integrated advantages of efficient enrichment, fast magnetic separation, and strong localized surface plasmon resonance properties of AgNPs. With versatile merits, TPA and OFX can be enriched and separated within 10 min. SERS methods for analysis of TPA and OFX were developed with detection limits of 35.5 μg/L and 15.8 μg/L, respectively. TPA and OFX were actually found in aquatic product, and recoveries during sample analysis were 89.3%-110% for TPA and 89.3%-96.8% for OFX. The analytical process completed within 30 min via enrichment-separation-detection all-in-one, exhibiting great potential for rapid analysis of toxic biogenic monoamines and antibiotic residues in food.


Involvement of SIRT1 in hypoxic down-regulation of c-Myc and β-catenin and hypoxic preconditioning effect of polyphenols.
SIRT1 has been found to function as a Class III deacetylase that affects the acetylation status of histones and other important cellular nonhistone proteins involved in various cellular pathways including stress responses and apoptosis. In this study, we investigated the role of SIRT1 signaling in the hypoxic down-regulations of c-Myc and β-catenin and hypoxic preconditioning effect of the red wine polyphenols such as piceatannol, myricetin, quercetin and resveratrol. We found that the expression of SIRT1 was significantly increased in hypoxia-exposed or hypoxic preconditioned HepG2 cells, which was closely associated with the up-regulation of HIF-1α and down-regulation of c-Myc and β-catenin expression via deacetylation of these proteins. In addition, blockade of SIRT1 activation using siRNA or amurensin G, a new potent SIRT1 inhibitor, abolished hypoxia-induced HIF-1α expression but increased c-Myc and β-catenin expression. SIRT1 was also found to stabilize HIF-1α protein and destabilize c-Myc, β-catenin and PHD2 under hypoxia. We also found that myricetin, quercetin, piceatannol and resveratrol up-regulated HIF-1α and down-regulated c-Myc, PHD2 and β-catenin expressions via SIRT1 activation, in a manner that mimics hypoxic preconditioning. This study provides new insights of the molecular mechanisms of hypoxic preconditioning and suggests that polyphenolic SIRT1 activators could be used to mimic hypoxic/ischemic preconditioning.


1,2-migration in rhodium(II) carbene transfer reaction: remarkable steric effect on migratory aptitude.
A series of diazo carbonyl compounds bearing different substituents have been prepared in order to investigate the steric effect in 1,2-migration reaction of rhodium(II) carbene. Through the investigation on the diazo decomposition of these compounds with Rh2(OAc)4, it was found that the steric effect could dramatically influence the migratory aptitude. In many cases, the steric effect could override the inherent electronic effect of the substituent.


Trends for Stage and Grade Group of Prostate Cancer in the US (2010-2016).
To quantify the yearly prostate cancer incidence per 100,000 men, comparing consecutive years from 2010 through 2016. In the years immediately following the 2011/2012 U.S. Preventive Services Task Force update to prostate specific antigen (PSA) screening guidelines, PSA screening, biopsy, and subsequent prostate cancer diagnosis and definitive local treatment have declined. We performed an analysis of stage and grade at diagnosis for prostate cancer in the US, in the years following the 2011/2012 update. This was a retrospective study performed using the Surveillance, Epidemiology, and End Results Program data. Inclusion criteria were men ≥ 40 years with prostate cancer diagnosed between the years 2010 and 2016. In total, 370,865 cases of prostate cancer were analyzed. Overall, the incidence of prostate cancer decreased from 522 to 327 cases per 100,000 persons from 2010 to 2016. Conversely, the rate of metastatic disease increased over this duration from 29 to 37 cases per 100,000 persons (P< .05). In patients ≥70 years, this increase was from 21 to 27 cases per 100,000 persons over the 7 years (P < .05). High-grade disease incidence did not change significantly over the study period, though low-grade disease incidence, (Grade Groups 1 and 2) decreased from 204 and 155 to 116 and 115 cases per 100,000 persons, respectively (P < .05). In the years following the 2011/2012 recommendation against PSA screening, fewer localized prostate cancers and more distantly metastatic prostate cancers were diagnosed. Most increases in metastatic disease was among men ≥70 years.


An unusual case of IgE myeloma.
A further case of IgE myeloma in a 65 year old woman was described. An unusual picture was found in the urine where two IgE fragments, namely an incomplete Fc fragment and an IgE specific Fab fragment were excreted. The clinical picture supports the suggestion that IgE myelomas are very heterogenous.


Effect of atropine on food-stimulated gastrin release after truncal vagotomy in man.
Studies have been performed on man after truncal vagotomy to ascertain the effect of 1.2 mg of atropine sulfate on basal and postprandial immunoreactive gastrin. Atropine had no effect on basal gastrin, but it caused a significant increase in both the peak postprandial gastrin (135 to 240 pg per ml without the 139 to 308 pg per ml with atropine) and the integrated gastrin response (10.2 and 15.5 ng-min per ml over 2 hr respectively). This indicates that vagal integrity is not essential for the enhancement of the gastrin response by atropine and implies a direct effect on the antral gastrin cell.


Localization of individual subunits of protein kinase CK2 to the endoplasmic reticulum and to the Golgi apparatus.
The protein kinase CK2 is composed of two catalytic alpha- or alpha'- and two regulatory beta-subunits. In mammalian cells there is ample evidence for the presence of individual CK2 subunits beside the holoenzyme. By immunofluorescence studies using peptide antibodies which allow us to detect the CK2alpha-, alpha'- and beta-subunits we found all three subunits to be co-localized with a 58 KDa Golgi protein which is specific for the Golgi complex. Subfractionation studies using dog pancreas cells revealed the presence of all three subunits of CK2 at the smooth endoplasmic reticulum (sER)/Golgi fraction whereas the rough endoplasmic reticulum (rER) harboured only the catalytic alpha- and alpha'-subunits. We found that the microsomal preparation from dog pancreas cells contained CK2 which phosphorylated a CK2 specific synthetic peptide and which was heparin sensitive. Furthermore, we could immunoprecipitate the CK2alpha-subunit that exhibited a kinase activity which phosphorylated a CK2 specific substrate and which was heparin sensitive. Protease digestion experiments revealed that the CK2 subunits were located on the cytosolic side of the rER and the sER/Golgi complex. Thus, we could demonstrate an asymmetric distribution of the CK2 subunits at the rER and sER/Golgi complex. Since the CK2alpha- and alpha'-subunits exhibit a substrate specificity which is different from the CK2 holoenzyme one might speculate that the asymmetric distribution of the CK2 holoenzyme and the CK2 catalytic subunits may have regulatory functions.


Effects of radiofrequency channel numbers on B1+ mapping using the Bloch-Siegert shift method.
This paper aims to investigate the impact of the channel numbers on the performance of B1+ mapping, by using the Bloch-Siegert shift (BSS) method. B1+ mapping plays a crucial role in various brain imaging protocols. We simulated the radiofrequency field of the human head model in six groups of multi-channel receive coil with a range of different channel numbers. MR signals were synthesized according to the standard BSS sequence, with quantified Gaussian added. Next, we combined the signals of each channel to reconstruct the B1+ map by weighted averaging and maximum likelihood estimation strategies and evaluate the bias by relative standard deviation of each coil. The simulation results revealed that the accuracy of B1+ maps improved with the increasing of channel numbers, meanwhile the per channel efficiency of B1+maps accuracy gradually decrease. Both trends slowed down when the channel numbers reached 12 or above. Our finding suggests that increasing the channel numbers can improve the accuracy of B1+map. However, a diminishing efficiency of per channel accuracy improvement was overserved, indicating that the relationship between quality of B1+ map and the channel numbers is nonlinear. Based on these findings, our study provides a reference for determining channel numbers to achieve a balance of coil selection and manufacturing cost. It also provides a theoretical basis for evaluating other B1+ mapping techniques.


Imidacloprid/moxidectin topical solution for the prevention of heartworm disease and the treatment and control of flea and intestinal nematodes of cats.
Sixteen controlled laboratory studies, involving 420 kittens and cats, were conducted to evaluate the efficacy and safety of topically applied formulations of imidacloprid and moxidectin for the prevention of feline heartworm disease, treatment of flea infestations and treatment and control of intestinal nematodes. Unit-dose applicators and the dosing schedule used in these studies were designed to provide a minimum of 10mg imidacloprid and 1mg moxidectin/kg. Treatments were applied topically by parting the hair at the base of the skull and applying the solution on the skin. Imidacloprid treatment alone did not display activity against Dirofilaria immitis or intestinal nematodes and moxidectin treatment alone provided little or no activity against adult Ctenocephalides felis infestations. The formulation containing 10% imidacloprid and 1% moxidectin was 100% efficacious against the development of adult D. immitis infections when cats were treated 30 days after inoculation with third-stage larvae. A single treatment with this formulation also provided 88.4-100% control of adult C. felis for 35 days. Imidacloprid/moxidectin was 100% efficacious against adult Toxocara cati and 91.0-98.3% efficacious against immature adults and fourth-stage T. cati larvae. The formulation provided 98.8-100% efficacy against adult Ancylostoma and immature adults and third-stage A. tubaeforme larvae. Monthly topical application with 10% imidacloprid/1% moxidectin is convenient, efficacious and safe for the prevention of feline heartworm disease, treatment of flea infestation and for the treatment and control of intestinal nematode infections of cats.


From Simple to Architecturally Complex Hydrogel Scaffolds for Cell and Tissue Engineering Applications: Opportunities Presented by Two-Photon Polymerization.
Direct laser writing via two-photon polymerization (2PP) is an emerging micro- and nanofabrication technique to prepare predetermined and architecturally precise hydrogel scaffolds with high resolution and spatial complexity. As such, these scaffolds are increasingly being evaluated for cell and tissue engineering applications. This article first discusses the basic principles and photoresists employed in 2PP fabrication of hydrogels, followed by an in-depth introduction of various mechanical and biological characterization techniques used to assess the fabricated structures. The design requirements for cell and tissue related applications are then described to guide the engineering, physicochemical, and biological efforts. Three case studies in bone, cancer, and cardiac tissues are presented that illustrate the need for structured materials in the next generation of clinical applications. This paper concludes by summarizing the progress to date, identifying additional opportunities for 2PP hydrogel scaffolds, and discussing future directions for 2PP research.


What are we determining using gas chromatographic multiresidue methods: tralomethrin or deltamethrin?
The analytical behaviour of the relatively new pyrethroid insecticide tralomethrin has been evaluated by using gas chromatography (GC) with electron-capture and mass spectrometry (MS) detectors, and liquid chromatography (LC)-atmospheric pressure ionization mass spectrometry with electrospray interfacing. Under the GC conditions commonly used in pesticide residue analysis, it was found that tralomethrin is transformed into deltamethrin (in a reproducible way) in the injector port of the GC system. Results obtained in this work indicate that the GC multiresidue methodologies routinely applied in the analysis of pyrethroid pesticides in foods cannot distinguish between these two pesticides, and the chromatographic signal obtained at the retention time of deltamethrin/tralomethrin can be really quantified as either deltamethrin or tralomethrin, including when it is confirmed as deltamethrin by MS. Under the LC-MS conditions assessed in this work, deltamethrin and the two diasteroisomers of tralomethrin were well separated and identified.


Effects of pentobarbital and veratridine on phosphatidylinositol and phosphatidate metabolism in rat parotid acinar cells.
The metabolism of phosphatidylinositol and phosphatidate was studied in isolated rat parotid cells, incubated in a physiological buffer containing [32P]phosphate or [3H]glycerol. Carbamylcholine and epinephrine stimulated 32P incorporation into both of these phospholipids, causing their half-maximal effects at 2 and 0.8 microM respectively. The former concentration is much lower than that anticipated from binding studies. The Hill coefficients for carbamylcholine activation of 32P incorporation were 0.61 +/- 0.05 for phosphatidate and 0.64 +/- 0.05 for phosphatidylinositol. Pentobarbital (0.58 mM) inhibited the increased 32P incorporation caused by 5 microM carbamylcholine but not 100 microM carbamylcholine. Pentobarbital inhibited the incorporation of 3H equally in the presence and absence of epinephrine, indicating that the effect of pentobarbital on 32P incorporation is on turnover and not on de novo synthesis. Veratridine (200 microM) had no effect on phospholipid metabolism in the presence and absence of either carbamylcholine or epinephrine, which contrasts with our previous findings in synaptosomes [J.C. Miller and I. Leung, Biochem. J. 178, 9 (1979)].


Gastrointestinal symptoms in office workers are predicted by psychological distress and short sleep duration.
Gastrointestinal (GI) symptoms can be triggered by several lifestyle factors, including psychological distress, short sleep duration, and diet. It is poorly known which physiological mechanisms are involved, but the autonomic nervous system (as a key mediator of the stress response) is a likely candidate. We aimed to investigate the associations between selected lifestyle factors, measures of stress physiology, and GI symptoms. This is a longitudinal study of 1002 office employees (52% male, mean age 39 ± 10 years), who were asked to report their GI symptoms, psychological distress, sleep times, and intake of caffeine, alcohol, and soft drinks for 5 days. Skin conductance, heart rate / variability, and acceleration were automatically recorded using wearable sensors. 850 participants from this study were eligible for analysis. We computed within-person correlations between the variables and used mediation analysis to test causal models. Sleep duration (ρ = -0.12, p < 0.001) and psychological distress (ρ = 0.19, p < 0.001) were significantly though weakly associated with GI symptoms. The physiological variables were not or weakly associated with GI symptoms in this study. The association between sleep duration and GI symptoms was largely mediated by psychological distress (61%). Short sleep and psychological distress predict GI symptoms in office workers. Further research is needed to unravel the physiological mechanisms mediate this association.


Operation Remote Immunity: exploring the impact of a service-learning elective in remote Indigenous communities.
The novel coronavirus, COVID-19, emerged in December 2019. Shortly after, vaccines against the virus were distributed in Canada for public use, but the remoteness of many northern Indigenous communities in Ontario posed a challenge for vaccine distribution and dissemination. The Ministry of Health partnered with the Northern Ontario School of Medicine University (NOSMU) and the air ambulance service, Ornge, to assist in delivering the vaccination doses to 31 fly-in communities in the Nishnawbe Aski Nation and Moosonee, all within Ontario. These deployments were considered "service-learning electives" for Undergraduate and Postgraduate medical learners from NOSMU who joined the operation in two-week deployments. NOSMU is renowned for its social accountability mandate and gives its medical learners opportunities to participate in service-learning to enhance their medical skills and cultural sensitivity. The purpose of this study is to examine the relationship between social accountability and medical learners' experiences during a service-learning elective in northern Indigenous communities in Ontario during the COVID-19 pandemic. Data were collected through a planned post-placement activity completed by eighteen Undergraduate and Postgraduate medical learners, who participated in the vaccine deployment. The activity consisted of a 500-word reflective response passage. Thematic analysis was used to identify, analyze, and report the themes within the collected data. Two themes were identified by the authors, which formed a concise overview of the collected data: (1) confronting the realities of working in Indigenous communities; and (2) service-learning as a path to social accountability. These vaccine deployments were an opportunity for medical learners to engage in service-learning and engage with Indigenous communities in Northern Ontario. Service-learning is an exceptional method which provides an opportunity to expand knowledge on the social determinants of health, social justice, and social accountability. The medical learners in this study reiterated the idea that learning medicine through a service-learning model leads to a greater depth of knowledge on Indigenous health and culture, and enhances medical knowledge compared to classroom learning.


The effects of gene polymorphisms on glioma prognosis.
Malignant gliomas are the most common primary brain tumors. Various genetic factors play important roles in the development and prognosis of glioma. The present study focuses on the impact of MPHOSPH6, TNIP1 and several other genes (ACYP2, NAF1, TERC, TERT, OBFC1, ZNF208 and RTEL1) on telomere length and how this affects the prognosis of glioma. Forty-three polymorphisms in nine genes from 605 glioma patients were selected. The association between genotype and survival outcome was analyzed using the Kaplan-Meier method, Cox regression analysis and the log-rank test. The 1-year overall survival (OS) rates of patients younger than 40 years of age was higher compared to those in patients older than 40 years of age. The 1-year OS rate of patients who underwent total resection was higher than that of patients whose gliomas were not completely resected. The 1-year OS rates of patients undergoing chemotherapy and of patients who did not undergo chemotherapy were 39.90% and 26.80%, respectively. Univariate analyses showed that ACYP2 rs12615793 and TERT rs2853676 loci affected progression-free survival in glioma patients; both ZNF208 rs8105767 and ACYP2 rs843720 affected the OS of patients with low-grade gliomas. Multivariate analyses suggested that MPHOSPH6 rs1056629 and rs1056654, and TERT rs2853676 loci were associated with good prognoses of patients with glioma or high-grade gliomas, whereas ZNF208 rs8105767 was associated with good prognosis of patients with low-grade glioma. Age, surgical resection and chemotherapy influenced the survival rates of glioma patients. TERT, MPHOSPH6, ACYP2 and ZNF208 genes were found to affect glioma prognosis.


Biomechanics--review of approaches for performance training in spinal manipulation.
Motor skills development is an inherent part of clinical training in health disciplines. The conscious use of educational theory to ground learning is receiving increasing attention across health care education. There are three distinct, yet overlapping, stages of motor skill learning; the cognitive, the integrative or associative, and the autonomous; in which a contextual framework for learning content may be structured. The learning is associated with a mapping of changes within the central nervous system by the interactive mechanisms of adaptation, use-dependent plasticity and operant reinforcement. Successful skill learning requires a sufficient amount of practice and the implementation of relevant feedback strategies in the form of knowledge of performance (KP) or knowledge of results (KR). There is a natural maturation of skills that may be accelerated by feedback. Several factors contribute to stronger skills development. "Mixture-of-experts" models systematically sequence tasks into logical blocks of theory, practice and student reflection on performance. Feedback should involve both KP and KR that compares performance to a tangible standard. Rehearsals should balance use of simulators and volunteer simulated patients to provide the full range of safe and effective learning opportunities prior to students accepting a role as care givers to the public in any clinical setting.


Factors associated with changes of care needs level in disabled older adults receiving home medical care: Prospective observational study by Osaka Home Care Registry (OHCARE).
To clarify factors associated with changes in care needs level and mortality among disabled older people receiving home medical care over a period of 2.5 years. The study included 179 participants, aged ≥65 years, receiving home medical care, who consented to join the Osaka Home Care Registry study. The main outcome was changes in the care needs level of participants eligible for the long-term care insurance system. We investigated the association of changes in care needs level with basic characteristics and care-receiving status. At the 2.5-year follow up, 20.0% of participants showed deteriorated levels, and 41.8% of participants died. In multiple logistic regression, age (odds ratio [OR] 1.10, 95% confidence interval [CI] 1.00-1.21; P = 0.051) and bone joint diseases (OR 0.34, CI 0.09-1.22; P = 0.098) were possible risks associated with deterioration of the care needs level. Male sex (OR 3.28, CI 0.91-11.74; P = 0.068) was a possible risk factor for mortality, and lower serum albumin (OR 0.22, CI 0.07-0.73) was a significant risk factor for mortality. We clarified the different factors associated with deterioration of the care needs level and mortality among disabled older people. Old age and bone joint diseases might be predictive factors for the further deterioration of independence of physical activity, and a low serum albumin level is considered to be strongly associated with increased mortality. Geriatr Gerontol Int 2019; 19: 1198-1205.


Repetitive stress-related injury of the proximal metacarpus in a seven-year old Thoroughbred racehorse with emphasis on diagnostic analgesia of the proximopalmar metacarpus.
This report describes the diagnosis and management of repetitive stress-related injury (RSRI) of the proximal metacarpus in a seven-year old Thoroughbred racehorse. Intra-articular analgesia of the middle carpal joint (MCJ) as well as perineural analgesia of the lateral palmar nerve (LPN) abolished lameness and a diagnosis of RSRI of the proximopalmar metacarpus was made after nuclear scintigraphic examination. Given the response to intra-articular analgesia, the authors undertook a cadaver study in order to better describe the relationship between the medial and lateral palmar pouches of carpo-metacarpal joint (CMCJ), the LPN and the deep branch of the lateral palmar nerve (DBLPaN).


Chronic imipramine treatment reduces (+)2-[125I]iodolysergic acid, diethylamide but not 125I-neuropeptide Y binding in layer IV of rat cerebral cortex.
The effects of chronic oral (2 X 10 mumol/kg, twice daily for 14 days) imipramine treatment on (+)2-[125I]-iodolysergic acid, diethylamide (125I-LSD) and 125I-neuropeptide Y (125I-NPY) receptor binding were examined in rat cerebral cortex by quantitative receptor autoradiography. A 35% reduction of 125I-LSD binding was observed in layer IV, both in the frontal and occipital cortex, while there was no significant change in 125I-NPY binding. The observed decrease in 125I-LSD binding is probably due to a reduction in the density of 5-hydroxytryptamine (5-HT) receptors of the 5-HT2 type. This reduction may represent a disturbance in the 5-HT synapses, regulating the transmission of the specific afferents innervating layer IV of the cerebral cortex.


Effects of inflammation and Plasmodium falciparum infection on soluble transferrin receptor and plasma ferritin concentration in different age groups: a prospective longitudinal study in Côte d'Ivoire.
Iron deficiency (ID) is a major cause of anemia, along with other nutritional, parasitic, and genetic factors. Accurate biomarkers are needed to estimate the relative contribution of ID to anemia. Soluble transferrin receptor (sTfR) is thought to be unaffected by inflammation. The objectives were to determine the difference in sTfR and plasma ferritin (PF) concentrations among infants (6-23 mo of age), school-age children (6-8 y of age), and women (15-25 y of age) with and without inflammation and with and without Plasmodium falciparum infection and to assess the effect of adjusting sTfR and PF for inflammation or for P. falciparum infection on the estimated prevalence of ID. The data were derived from a 14-mo prospective longitudinal survey on anemia, which was conducted in the Taabo area, south-central Côte d'Ivoire. At baseline, sTfR concentration was significantly higher in infants and school-age children with either inflammation or P. falciparum infection than in control individuals without inflammation or without P. falciparum infection. Individuals with inflammation had significantly higher PF concentrations than did subjects without inflammation. Adjustments in sTfR concentrations for inflammation or P. falciparum infection in infants and school-age children resulted in significantly lower ID prevalence. Adjustment of PF for inflammation and Plasmodium infection resulted in a higher ID prevalence in infants and women. In Ivorian infants and school-age children, ID prevalence was considerably lower after adjustment of sTfR for inflammation. However, as the prevalence estimates for ID differed widely if based on sTfR or PF, caution is still needed when estimating ID prevalence in areas with a high prevalence of inflammation or malaria. This trial was registered at controlled-trials.com as ISRCTN02181959.


Investigation of heavy metal and micro-macro element speciation in biomass ash enriched sewage sludge compost.
The objective of this study was to enrich the nutrient content of compost and to investigate the passivation and solubilization of plant micronutrients (Fe, Al, Cu, Ni, Zn, Na, Mn), macroelements (P, K, Mg, Ca), and heavy metals (Cr, Cd, Pb) during sewage sludge composting with nutrient-rich biomass ash additives. T0: 0%, T1: 3.5%, T2: 7.0%, and T3: 14.0% dry weight (DW), weight/weight (w/w) biomass ash was added to the sewage sludge + sawdust mixture (volume, 1:1) to obtain the final NPK content and monitored over a 45-day period. Sawdust was used as auxiliary material. The sequential extraction method was used to determine the elemental species. Cr, Cd and Pb showed higher affinity to the residual fraction and occluded in the oxide fraction, which decreased the bioavailability factor (BF) (<1% BF-Cr, 21% BF-Cd and 9% BF-Pb) compared to the control treatment (46% BF-Cr, 47% BF-Cd and 80% BF-Pb). As the amount of biomass ash increased (T1-T3), the percentages of residual Cr (Res-Cr) (10-65%), exchangeable Cd (Exc-Cd) and organically bound Cd (Org-Cd) (14% and 21%), and oxides-Pb (Oxi-Pb) (20-61%) increased. In all composts, Fe, Al, and Cu were associated with organically bound and oxides-entrapped fractions. More than 50% of total Mn and Mg were concentrated mainly in exchangeable fractions, suggesting high mobility and bioavailability (42% BF-Mn and 98% BF-Mg). Ni, Zn, and Na tended to be present in oxide-bound, organically bound, and residual fractions, while K and P were associated with exchangeable and organically bound fractions. The overall results suggest that composting sewage sludge with biomass ash may be the best strategy and technique to overcome soil application bottlenecks because it passivates heavy metals and improves the bioavailability of plant nutrients.


The skin: a mirror to the gut.
This review discusses the diseases with involvement of both skin and gut. GI manifestations of vesicobullous disorders and systemic diseases and syndromes involving skin and gut, dermatologic manifestations of inflammatory bowel disease (IBD), polyposis syndromes, and GI malignancies have been discussed. Diagnostic and treatment approaches towards these disorders are summarized. Interaction of the skin and gut has always been an area of inquisitiveness. Gastrointestinal (GI) tract can be involved in dermatological disorders or GI diseases can have a dermatological manifestation.


Observation of spin-dependent quantum jumps via quantum dot resonance fluorescence.
Reliable preparation, manipulation and measurement protocols are necessary to exploit a physical system as a quantum bit. Spins in optically active quantum dots offer one potential realization and recent demonstrations have shown high-fidelity preparation and ultrafast coherent manipulation. The final challenge-that is, single-shot measurement of the electron spin-has proved to be the most difficult of the three and so far only time-averaged optical measurements have been reported. The main obstacle to optical spin readout in single quantum dots is that the same laser that probes the spin state also flips the spin being measured. Here, by using a gate-controlled quantum dot molecule, we present the ability to measure the spin state of a single electron in real time via the intermittency of quantum dot resonance fluorescence. The quantum dot molecule, unlike its single quantum dot counterpart, allows separate and independent optical transitions for state preparation, manipulation and measurement, avoiding the dilemma of relying on the same transition to address the spin state of an electron.


Gliomas of the posterior fossa in adults.
Infratentorial gliomas are relatively rare tumors compared to their supratentorial counterparts. As such they have not been extensively characterized as a group and are usually excluded from clinical studies. Using our database we aimed to characterize adult gliomas involving the posterior fossa with respect to their clinical behavior and prognostic factors. We reviewed our neurosurgical and neuro-oncological data bases for adult patients diagnosed with gliomas involving the posterior fossa between 1996 and 2010. Of 1,283 glioma patients, 57 patients with gliomas involving the posterior fossa were identified (4.4 %). Tumors were further classified by location as primary brainstem (n = 21) and primary cerebellar (n = 18) tumors. On univariate analysis survival was correlated to tumor grade and KPS. In addition we have identified a unique group of patients (n = 18) with previously diagnosed supratentorial gliomas who subsequently developed noncontiguous secondary infratentorial extension of their tumors with subsequent rapid clinical deterioration. Gliomas of the posterior fossa comprise a heterogeneous group of tumors. Histological grade of the tumor was found to be the main prognostic factor. Survival of primary cerebellar gliomas is comparable to supra-tentorial gliomas, while brainstem gliomas in adults fare better than in the pediatric population. Secondary extension of supratentorial gliomas to the posterior fossa signifies a grave prognosis.


Effects of Nutrients on the Growth of and Free Exopolysaccharide Biosynthesis by Streptococcus thermophilus 937 in a Chemically Defined Medium.
The free exopolysaccharide (f-EPS) produced by Streptococcus thermophilus is a natural texture modifier with health-promoting properties and has thus become one of the most interesting metabolites for researchers. The present work aimed to further understand the nutritional requirements for the growth of and the f-EPS production by S. thermophilus. The types and concentrations of compounds in the complete chemically defined medium were changed in turn to evaluate the effects of single nutrients on the growth of and f-EPS production by S. thermophilus 937. The results showed that cysteine, glutamine, histidine, methionine, tryptophan, tyrosine, leucine, isoleucine, and valine played an important role in maintaining the rapid and stable growth of S. thermophilus 937. S. thermophilus 937 also required calcium pantothenate, niacin, pyridoxine, riboflavin, and thiamine hydrochloride as essential nutrients for growth. Increases in the concentrations of lactose, glutamate, histidine, or isoleucine significantly increased the production of free exopolysaccharide by S. thermophilus 937, and when the lactose concentration increased to 20 g·L-1 and the concentration of the three-amino-acid combination increased to 15 mM, the f-EPS yield increased to a maximum of 35.34 μg·mL-1. This finding indicated that lactose and the 3 amino acids exert synergistic effects on the promotion of f-EPS production. In addition, lactose and the three amino acids have strain specific promoting effects on f-EPS production by S. thermophilus. This study provides a further understanding of the effects of nutrients on the biosynthesis of f-EPS by S. thermophilus.


Dexamethasone inhibition of experimental endothelial cell proliferation in retinal venules.
The observation that endothelial cell proliferation in retinal blood vessels is induced by ocular trauma in rats has been extended to mice. Indomethacin, 10 mg/kg/day, failed to block incorporation of tritiated thymidine into nuclei of venular endothelial cells in rat retinas observed 40 hr after puncturing the lens, but dexamethasone effectively suppressed tritiated thymidine incorporation, with 50% inhibition obtained with 0.2 mg/kg/day. The prostaglandin pathway does not appear essential to the activation of endothelial cell proliferation in this system.


Autoantibodies from patients with complex regional pain syndrome induce pro-inflammatory effects and functional disturbances on endothelial cells in vitro.
Complex regional pain syndrome (CRPS) is an inadequate local response after a limb trauma, which leads to severe pain and autonomic and trophic changes of the affected limb. Autoantibodies directed against human β2 adrenergic and muscarinic M2 receptors (hβ2AR and hM2R) have been described in CRPS patients previously. We analyzed sera from CRPS patients for autoantibodies against hβ2AR, hM2R, and endothelial cells and investigated the functional effects of purified IgG, derived from 13 patients with CRPS, on endothelial cells. Eleven healthy controls, 7 radial fracture patients without CRPS, and 10 patients with peripheral arterial vascular disease served as control subjects. The CRPS-IgG, but not control IgG, bound to the surface of endothelial cells ( P < 0.001) and to hβ2AR and hM2R ( P < 0.05), the latter being reversed by adding β2AR and M2R antagonists. The CRPS-IgG led to an increased cytotoxicity and a reduced proliferation rate of endothelial cells, and by adding specific antagonists, the effect was neutralized. Regarding second messenger pathways, CRPS-IgG induced ERK1/2, p38, and STAT1 phosphorylation, whereas AKT phosphorylation was decreased at the protein level. In addition, increased expression of adhesion molecules (ICAM-1 and VCAM-1) on the mRNA level was induced by CRPS-IgG, thus inducing a pro-inflammatory condition of the endothelial cells. Our results show that patients with CRPS not only develop autoantibodies against hβ2AR and hM2R, but these antibodies also interfere with endothelial cells, inducing functional effects on these in vitro, and thus might contribute to the pathophysiology of CRPS.


The conversion of aryl sulfate ester salts to alkyl aryl derivatives suitable for analysis by electron impact mass spectrometry.
A series of monosubstituted (CH3, CH3O, Cl Br or NO2 at the O, m and p position) phenyl sulfate ester salts were derivatized to form n-propyl aryl sulfate diesters. The derivatization was accomplished by reacting aryl sulfate ester salts, AgClO4 and n-propyl iodide in SO2 at--40 degree C. The mass spectra of all the n-propyl aryl sulfate esters showed an intense molecular ion and intense diagnostic peaks at M--42 ([aryl--OSO3H]+) and M--122 ([ARYL--OH]+). The utility of this procedure for derivatizing selected sulfate ester conjugated xenobiotics and steroids was demonstrated.


Prospective cohort study of nonspecific deprescribing in older medical inpatients being discharged to a nursing home.
Older patients from nursing homes are commonly exposed to polypharmacy before a hospital admission. Deprescribing has been promoted as a solution to this problem, though systematic reviews have not found benefit. The aim of this study was to understand if in-hospital deprescribing of certain classes of medications is associated with certain benefits or risks. We conducted a prospective, multicentre, cohort study in 239 medical inpatients ⩾75 years (mean age 87.4 years) who were exposed to polypharmacy (⩾5 medications) prior to admission and discharged to a nursing home for permanent placement. Patients were categorised by whether deprescribing occurred, mortality and readmissions were assessed 30 and 90 days after hospital discharge. The EQ-5D-5 L health survey assessed changes in health-related quality of life (HRQOL) at 90 days, with comparison to EQ-5D-5 L results at day 30. Latent class analysis (LCA) was used to investigate associations between patterns of prescribed and deprescribed medications and mortality. Patients for whom deprescribing occurred had a higher Charlson Index; there were no differences between the groups in principal diagnosis, total or Beers list number of medications on admission. The number of Beers list medications increased in both groups before discharge. Patients who had medications deprescribed had nonsignificantly greater odds of dying within 90 days [odds ration (OR) = 3.23 (95% confidence interval (CI): 0.68, 14.92; p = 0.136]. Deprescribing of certain classes was associated with higher 90-day mortality: antihypertensives (OR = 2.27, 95% CI: 1.004, 5; p = 0.049) and statins (OR = 5, 95% CI: 1.61, 14.28; p = 0.005). Readmissions and 1-year mortality rates were similar. There was no deterioration in HRQOL when medications were deprescribed. LCA showed that patients with the least medication changes had the lowest mortality. Deprescribing certain classes of medications during hospitalisation was associated with worse mortality, but not readmissions or overall HRQOL. Larger controlled deprescribing studies targeting specific medications are warranted to further investigate these findings.This study was registered with the Australian and New Zealand Clinical Trials Registry, ACTRN1 2616001336471. Background: When an older person living in a nursing home is admitted to hospital, does stopping long-term medications help them?Many older people from nursing homes take a large number of medications each day to treat symptoms and prevent adverse events. "Polypharmacy" is a term used to describe taking multiple long-term medications, and it is associated with many negative outcomes such as increased number of falls, cognitive decline, hospital readmission, even death. Deprescribing of nonessential medications - whether stopping or reducing the dose - is promoted as good hospital practice and is assumed to help older frail people live longer and feel better. However, we often don't fully understand what is and is not essential.We wanted to better understand the effect of deprescribing long-term medications for older frail patients during an unplanned hospital admission as they were going to a nursing home to live.Methods: While admitted to hospital, medications are often reviewed by a clinical pharmacist and specialist physician. Sometimes medications are ceased; sometimes they are not. This gave us the opportunity to study two groups of older frail people from nursing homes: those who had regular, long-term medications ceased or reduced and those who did not. We wanted to see if one group did better. For example, did they feel worse if we stopped certain medications? Did they suffer other bad events compared with those patients for whom no medications were ceased? Were they readmitted to hospital earlier or more often?Results and conclusion: Despite the assumption that stopping medications for this type of patient is good practice, we found no benefit. We were also surprised to find stopping or reducing certain drug classes (e.g. antihypertensives and cholesterol-lowering drugs) was associated with greater mortality. Larger, randomised studies will better answer these important questions.


Hydroxylation of prostaglandins by inducible isozymes of rabbit liver microsomal cytochrome P-450. Participation of cytochrome b5.
The hydroxylation of prostaglandin (PG) E1, PGE2, and PGA1 was investigated in a reconstituted rabbit liver microsomal enzyme system containing phenobarbital-inducible isozyme 2 or 5,6-benzoflavone-inducible isoenzyme 4 of P-450, NADPH-cytochrome P-450 reductase, phosphatidylcholine, and NADPH. Significant metabolism of prostaglandins by isozyme 2 occurred only in the presence of cytochrome b5. Under these conditions, PGE1 hydroxylation was linear with time (up to 45 min) and protein concentration, and maximal rates were obtained with a 1:1:2 molar ratio of reductase: cytochrome b5:P-450LM2. Moreover, P-450LM2 catalyzed the conversion of PGE1, PGE2, and PGA1 to the respective 19- and 20-hydroxy metabolites in a ratio of about 5:1, and displayed comparable activities toward the three prostaglandins based on the total products formed in 60 min. Apocytochrome b5 or ferriheme could not substitute for intact cytochrome b5, while reconstitution of apocytochrome b5 with ferriheme led to activities similar to those obtained with the native cytochrome. Isozyme 4 of P-450 differed markedly from isozyme 2 in that it catalyzed prostaglandin hydroxylation at substantial rates in the absence of cytochrome b5, was regiospecific for position 19 of all three prostaglandins, and had an order of activity of PGA1 greater than PGE1 greater than PGE2. P-450LM4 preparations from untreated and induced animals had similar activities with PGE1 and PGE2, respectively. Addition of cytochrome b5 resulted in a 20 to 30% increase in the rate of PGE1 hydroxylation and an appreciably greater enhancement in the extent of all the P-450LM4-catalyzed reactions, the stimulation being greatest with PGE2 (3-fold) and least with PGA1 (1.6-fold). Cytochrome b5 was thus required for maximal metabolism of all three prostaglandins, but did not alter the regiospecificity or the order of activity of P-450 isozyme 4 with the individual substrates. In the presence of cytochrome b5, the prostaglandin hydroxylase activities of isozyme 4 were two to six times higher than those of isozyme 2.


5-Hydroxytryptamine and arachidonic acid metabolites modulate extensive platelet activation induced by collagen in cats in vivo.
1. The pathways contributing to the platelet adhesion/aggregation reaction elicited by collagen microfibrils, administered to cats in vivo, were analysed. 2. The intra-aortic infusion of collagen (100 micrograms kg-1 in 1 min) caused an extensive activation of platelets, as evidenced by the time-dependent drop of free platelet numbers in whole blood, and the increases of 5-hydroxyindoles (5-HI), 5-hydroxytryptamine (5-HT) and thromboxane B2 (TXB2) levels in plasma, prepared from effluent venous blood sampled from the inferior caval vein. 3. 5-HT2 receptor blockade with ketanserin (0.63 mg kg-1 i.v., 10 min) and cyclo-oxygenase inhibition with aspirin (10 mg kg-1 i.v., 10 min) slightly attenuated the peak reduction of free platelets in whole blood in response to collagen without affecting changes in plasma 5-HI. Aspirin, but not ketanserin, reduced the collagen-induced changes in plasma TXB2, prostaglandin E2 (PGE2) and 6K-PGF1 alpha. 4. Dual TXA2 synthetase inhibition/TXA2-prostaglandin endoperoxide receptor antagonism with ridogrel (5 mg kg-1 i.v., 10 min) halved the drop in free platelets, reduced the release of platelet 5-HI, inhibited the increase in plasma TXB2 and elevated that of 6K-PGF1 alpha and PGE2 in response to collagen. 5. Combined treatment with ketanserin and aspirin reduced the collagen-induced drop of free platelets and the release of platelet 5-HI to a similar extent as ridogrel alone; plasma prostanoids were affected as with aspirin alone. 6. Combined administration of ketanserin and ridogrel virtually eliminated the collagen-induced platelet adhesion/aggregation response and release of 5-HI; prostanoids were affected as with ridogrel alone. 6. Combined administration of ketanserin and ridogrel virtually eliminated the collagen-induced platelet adhesion/aggregation response and release of 5-HI; prostanoids were affected as with ridogrel alone. 7. The results indicate that the interplay between 5-HT and arachidonic acid metabolites is causally involved in the platelet reaction to activation induced by collagen in cats in vivo.


Susceptibility and disease modifier genes in amyotrophic lateral sclerosis: from genetic associations to therapeutic implications.
Amyotrophic lateral sclerosis (ALS) is a severe disease characterized by the degeneration of motor neurons. Large-scale genetic studies have now identified over 60 genes that are associated with ALS, which in large part have also been functionally characterized. The purpose of this review is to outline how these advances are being translated into novel therapeutic strategies. The emergence of techniques that allow the specific therapeutic targeting of a (mutant) gene, in particular antisense oligonucleotide therapy (ASOs), have led to the first successful gene therapy for SOD1-ALS and multiple other gene-targeted trials are underway. This includes genetic variants that modify the disease phenotype as well as causal mutations. Technological and methodological advances are enabling researchers to unravel the genetics of ALS. Both causal mutations and genetic modifiers are viable therapeutic targets. By performing natural history studies, the phenotype-genotype correlations can be characterized. In conjunction with biomarkers for target engagement and international collaboration, this makes performing gene-targeted trials ALS feasible. The first effective treatment has now been developed for SOD1-ALS and, with multiple studies underway, it seems realistic that more therapies will follow.


[Metabolism of methionine in tissues of cattle in vitro].
After incubation of homogenates of liver, kidney, brain, skeletal muscles mucosa of rumen and empty intestine of cattle in Krebs-Ringer's phosphate buffer with [2-14C]methionine 25.8-43.4% radioactive label was found in protein; 28.1-42.0%, in CO2; 12.0-18.6%, in glucose; 8.2-14.9%, in glycogen; 3.1-6.3%, in lipids. The highest level of [2-14C]methionine utilization in protein synthesis was found in skeletal muscle; in energetical processes, in liver; in the process of gluconeogenesis, in skeletal muscles and liver; in lipid synthesis, in brain; the lowest level of [2-14C]methionine utilisation in above-mentioned process was found in skin.


Growth inhibition of S. cerevisiae, B. subtilis, and E. coli by lignocellulosic and fermentation products.
This paper describes the effect of several inhibiting components on three potential hosts for the bio-based production of methyl propionate, namely, wild-type Escherichia coli and Bacillus subtilis, and evolved Saccharomyces cerevisiae IMS0351. The inhibition by the lignocellulose-derived products 5-hydroxymethyl-2-furaldehyde, vanillin, and syringaldehyde and the fermentation products 2-butanol, 2-butanone, methyl propionate, and ethyl acetate has been assessed for these strains in defined medium. Multiple screenings were performed using small-scale cultures in both shake flasks and microtiter plates. Technical drawbacks revealed the limited applicability of the latter in this study. The microbial growth was characterized by means of a lag-time model, and the inhibitory thresholds were determined using product-inhibition models. The lignocellulose-derived products were found to be highly inhibitory, and none of the strains could grow in the presence of 2.0 g L-1 of product. From the fermentation products tested, methyl propionate had the most severe impact resulting in complete inhibition of all the strains when exposed to concentrations in the range of 12-18 g L-1. In general, S. cerevisiae and B. subtilis were comparatively more tolerant than E. coli to all the fermentation products, despite E. coli's lower sensitivity towards vanillin. The results suggest that, overall, the strains investigated have good potential to be engineered and further established as hosts for the bio-based production of methyl esters.


Simulation of spaceflight with whole-body head-down tilt: influence on intraocular pressure and retinocortical processing.
Cephalad fluid shifts occur in the microgravity environment of spaceflight. Whole-body head-down tilt was used to simulate the influence of these fluid shifts upon intraocular pressure (IOP) and the bioelectrical activity of neural elements in the retinocortical pathway. Noninvasive techniques were used to monitor IOP, pattern reversal electroretinograms (prERGs), and pattern reversal visual evoked cortical potentials (prVEPs) when subjects were oriented either upright or in a head-down position (6 degrees or 90 degrees). The results indicate that there is a significant elevation in IOP when an individual is oriented in a head-down position. Significant alterations of neurophysiological processing in the retinocortical pathway also occur when individuals are oriented in a head-down position.


Paraquat exposure induces behavioral deficits in larval zebrafish during the window of dopamine neurogenesis.
Exposure to environmental risk factors such as herbicides in early life has been proposed to play important roles in the development of neurodegenerative disorders in adult life. To test this hypothesis, we used a zebrafish model to link the herbicide paraquat (PQ) to disease etiology. Strikingly, treatment of 18 hpf embryonic zebrafish with low-dose PQ treatment (0.04 ppm, lower than the accepted human daily exposure) resulted in 50% display of neurodegenerative phenotypes and motor deficits at various developmental stages (segmentation to larval stage). Wide arrays of biomarkers have been employed to delineate the toxic responses which include lipid peroxidation, glutathione (GSH) and apoptosis studies. A decrease in the GSH levels, increase in lipid peroxidation and apoptosis, respectively, were observed at various developmental stages. Unexpectedly, we show that the exposure to paraquat during the window of dopamine neurogenesis causes Parkinsonian like motor defects in later life by perturbing cholinergic system due to oxidative stress.


Dependence of motoneurone properties on the length of immobilized muscle.
1. The soleus muscle of adult cats was fixed in a shortened or lengthened position for 2 weeks by immobilizing the leg with a plaster cast. To eliminate the effects of reflex activity arising from the muscle, the lumbosacral dorsal roots were sectioned on the side of leg immobilization.2. The soleus muscle showed a significant decrease in weight after immobilization in a shortened position. Immobilization of the muscle in a lengthened position produced no significant changes in its weight.3. Two weeks after transection of the throacic spinal cord, the soleus muscle showed a significant decrease in weight. This decrease was prevented by immobilization of the muscle in a lengthened position. Immobilization in a shortened position caused no further muscle atrophy in cord-transected animals.4. Soleus motoneurones showed a significant decrease in the duration of after-hyperpolarization (a.h.p.) 2 weeks after immobilization of the muscle in a shortened position, whereas immobilization of the muscle in a lengthened position caused no significant changes in the duration of a.h.p.5. A decrease in the duration of a.h.p. of soleus motoneurones induced by cord transection was significantly prevented by immobilization of the muscle in a lengthened position but not by immobilization in a shortened position.6. In a variety of experimental conditions, the mean duration of a.h.p. of soleus motoneurones was significantly correlated with the soleus muscle: body wt. ratio.7. It is concluded that certain motoneurone properties depend upon the condition of the innervated muscle and that the primary factor responsible for the trophic influence is metabolic change in the muscle rather than contractile activity itself.


Effectiveness of non-pharmacological and non-surgical interventions on the impact of rheumatoid arthritis: an umbrella review protocol.
The questions of this review are.


Reversible paraneoplastic encephalitis in three patients with ovarian neoplasms.
Anti-N-methyl-d-aspartate (NMDA) receptor encephalitis is a recently described potentially lethal but treatable disorder that often occurs as a paraneoplastic manifestation of ovarian teratomas. We report three women with this disorder who presented with subacute onset of delirium, seizures and autonomic instability. Anti-NMDA receptor antibodies were detectable in the serum or cerebrospinal fluid of each patient. Ovarian masses were detected in two patients, and subsequently excised. In the third patient, an empirical bilateral salpingo-oophorectomy was performed and revealed a microscopic neoplasm. All patients experienced slow reversal of the neurological symptoms following surgery and immunotherapy. Our experience suggests that prompt syndrome recognition followed by tumor removal and immunotherapy usually results in neurological recovery.


Heat transfer enhancement in cryogenic quenching process.
This paper reports a heat transfer advancement in the cryogenic quenching process. An experiment was performed to evaluate the enhancement of quenching heat transfer by the use of metal tubes with low thermal conductivity coating layers. Four coating thicknesses with various coolant mass flow rates of liquid nitrogen were investigated. The results indicated that the tube inner surface coating greatly enhanced the quenching efficiency. The quenching efficiency was found to increase with increasing number of coating layers, and the efficiency also increased with decreasing mass flow rates. In general, the efficiencies cover a range between 40.6% and 80%. Comparing to the bare surface case, the percentage increase in the quenching efficiency was the minimum at 4.2% for a single coated layer at the highest flow rate and the maximum of 109.1% for four coated layers at the lowest flow rate. The coated tubes could save up to 53% in the amount of cryogen consumption.


Insulin-stimulated muscle glucose clearance in patients with NIDDM. Effects of one-legged physical training.
Physical training increases insulin action in skeletal muscle in healthy men. In non-insulin-dependent diabetes mellitus (NIDDM), only minor improvements in whole-body insulin action are seen. We studied the effect of training on insulin-mediated glucose clearance rates (GCRs) in the whole body and in leg muscle in seven patients with NIDDM and in eight healthy control subjects. One-legged training was performed for 10 weeks. GCR in whole body and in both legs were measured before, the day after, and 6 days after training by hyperinsulinemic (28, 88, and 480 mU x min(-1) x m(-2)), isoglycemic clamps combined with the leg balance technique. On the 5th day of detraining, one bout of exercise was performed with the nontraining leg. Muscle biopsies were obtained before and after training. Whole-body GCRs were always lower (P < 0.05) in NIDDM patients compared with control subjects and increased (P < 0.05) in response to training. In untrained muscle, GCR was lower (P < 0.05) in NIDDM patients (13 +/- 4, 91 +/- 9, and 148 +/- 12 ml/min) compared with control subjects (56 +/- 12, 126 +/- 14, and 180 +/- 14 ml/min). It Increased (P < 0.05) in both groups in response to training (43 +/- 10, 144 +/- 17, and 205 +/- 24 [NIDDM patients] and 84 +/- 10, 212 +/- 20, and 249 +/- 16 ml/min [control subjects]). Acute exercise did not increase leg GCR. In NIDDM patients, the effect of training was lost after 6 days, while the effect lasted longer in control subjects. Training increased (P < 0.05) muscle lactate production and glucose storage as well as glycogen synthase (GS) mRNA in both groups. We conclude that training increases insulin action in skeletal muscle in control subjects and NIDDM patients, and in NIDDM patients normal values may be obtained. The increase in trained muscle cannot fully account for the increase in whole-body GCR. Improvements in GCR involve enhancement of insulin-mediated increase in muscle blood flow and the ability to extract glucose. They are accompanied by enhanced nonoxidative glucose disposal and increases in GS mRNA. The improvements in insulin action are short-lived.


Interactions among irradiance, nutrients, and herbivores constrain a stream algal community.
Using stream-side, flow-through channels, I tested for the effects of nutrients (NU) (nitrogen plus phosphorus), irradiance (L), and snail grazing (G) on a benthic algal community in a small, forested stream. Grazed communities were-dominated by a chlorophyte (basal cells ofStigeoclonium) and a cyanophyte (Chamaesiphon investiens), whereas ungrazed communities were comprised almost entirely of diatoms, regardless of nutrient and light levels. Snails maintained low algal biomass in all grazed treatments, presumably by consuming increased algal production in treatments to which L and NU were increased. When nutrients were increased, cellular nutrient content increased under ambient conditions (shaded, grazed) and biomass and productivity increased when snails were removed and light was increased. Together, nutrients and light had positive effects and grazing had negative effects on biomass (chlorophylla, AFDM, algal biovolume) and chlorophyll-and areal-specific productivity in ANOVAs. However, in most cases, only means from treatments in which all three factors were manipulated (ungrazed, +NU&L treatments) were significantly different from controls; effects of single factors were generally undetectable. These results indicate that all three factors simultaneously limited algal biomass and productivity in this stream during the summer months. Additionally, the effects of these factors in combination were in some cases different from the effects of single factors. For example, light had slight negative effects on some biomass parameters when added at ambient snail densities and nutrient concentrations, but had strong positive effects in conjunction with nutrient addition and snail removal. This study demonstrates that algal biomass and productivity can be under multiple constraints by irradiance, nutrients, and herbivores and indicates the need to employ multifactor experiments to test for such interactive effects.


Phototoxicity of Hemoporfin to ovarian cancer.
Hematoporphyrin monomethyl ether (Hemoporfin) is a novel porphyrin-related photosensitizer. Photocytotoxic effect of Hemoporfin to ovarian cancer is still unclear. We used human epithelial ovarian carcinoma cell line SKOV3 and its xenograft model in nude mice to investigate the Hemoporfin-based photodynamic therapy (PDT) for ovarian cancer. The growth rates of SKOV3 cells were determined by MTT assays. Flow cytometry combined with dual Annexin V/PI staining was used to identify the death mode of the cells following PDT. We demonstrated that Hemoprofin-based PDT induced significant cell death via direct necrosis induction, and the photocytotoxity to SKOV3 cells is dose related. With SKOV3 xenograft model in nude mouse, we further demonstrated that Hemoporfin-based PDT is effective for controlling the tumor growth. Our results suggest that Hemoporfin is a promising novel photosensitizer for the treatment of ovarian cancer and merit further evaluation in the clinical practice.


Biosynthetic Electronic Interfaces for Bridging Microbial and Inorganic Electron Transport.
Electron transport in biological and inorganic systems is mediated through distinct mechanisms and pathways. Their fundamental mismatch in structural and thermodynamic properties has imposed a significant challenge on the effective coupling at the biotic/abiotic interface, which is central to the design and development of bioelectronic devices and their translation toward various engineering applications. Using electrochemically active bacteria, such as G. sulfurreducens, as a model system, here we report a bottom-up, biosynthetic approach to synergize the electron transport and significantly enhance the coupling at the heterogeneous junction. In particular, graphene oxide was exploited as the respiratory electron acceptors, which can be directly reduced by G. sulfurreducens through extracellular electron transfer, closely coupled with outer membrane cytochromes in electroactive conformation, and actively "wire" the redox centers to external electrical contacts. Through this strategy, the contact resistance at the biofilm/electrode interface can be effectively reduced by 90%. Furthermore, the cyclic voltammetry reveals that the electron transfer of the DL-1 biofilm transformed from a low-current (∼0.36 μA), rate-limited profile to a high-current (∼5 μA), diffusion-limited profile. These results suggested that the integration of rGO can minimize the charge transfer barriers at the biofilm/electrode interface. The more transparent contact at the DL-1/electrode interface also enables unambiguous characterization of the inherent electron transport kinetics across the electroactive biofilm independent of cell/electrode interactions. The current work represents a strategically new approach toward the seamless integration of biological and artificial electronics, which is expected to provide critical insights into the fundamentals of biological electron transport and open up new opportunities for applications in biosensing, biocomputing, and bioenergy conversion.


Tumor necrosis factor-alpha at the crossroads of neuronal life and death during HIV-associated dementia.
Human immunodeficiency type-1 (HIV-1) infection is known to cause disorders of the CNS, including HIV-associated dementia (HAD). It is suspected that tumor necrosis factor-alpha (TNF-alpha) released by infected microglia and macrophages play a role in neuronal injury seen in HAD patients. Accordingly, studies suggest that the level of TNF-alpha mRNA increases with increasing severity of dementia in patients, and that inhibitors of TNF-alpha release reduces neuronal injury in murine model of HAD. However, the exact role of TNF-alpha in relation to neuronal dysfunction is a matter of ongoing debate. One school of thought hails TNF-alpha as the inducer and mediator of neurodegeneration and their evidence suggest that TNF-alpha kill neurons directly by recruiting caspases or may kill indirectly by various means. In sharp contrast to this, another concept theory envisages a role for TNF-alpha in negotiating neuroprotection during HAD. The current compilation examines these contradictory concepts, and evaluates their efficacy in the light of TNF-alpha signaling. It also attempts to elaborate the current consensus outlook of TNF-alpha's role during HAD.


An arterial prosthesis from Argentina: the Barone Microvelour arterial graft.
The manufacture of a polyester vascular prosthesis in the southern hemisphere is a new development in the global dissemination of this maturing technology. Hence the recent introduction of the Barone Microvelour arterial graft from Argentina has highlighted the need for a comparative in vitro and in vivo study to compare its structure and performance with that of existing commercial products. Following a series of laboratory tests and implantations as a thoracoabdominal bypass in dogs, the Barone Microvelour has been identified as a strong graft constructed after the style of early weft-knitted designs. It provides an equivalent sequence and rate of healing to that of other polyester knitted grafts.


Barriers to reforming healthcare: the Italian case.
Using the conceptual lenses offered by the ideational and cultural path taken in the health care arena, this article attempts to explain the trajectory of recent major health care reforms in Italy and the reasons for their failure, as well as providing some directions for successful intervention. A diachronic analysis of the relatively under-investigated phenomenon of health care reforms in Italy is carried out, drawing on a systematic review of the Italian and international literature combined with the research work carried out by the Author. For all the three major health reforms examined, a significant gap between the authoritative policy choices taken and the overall implementation, in terms of process and system changes, can be observed, determining a growing distance between the theoretical efficiency and the practical effectiveness of the Italian National Health Service (NHS) as well as its detachment from the social system. The main obstacle to effective reform seems to be the cultural hegemony of the administrative-managerial and the biomedical paradigms, which, by reinforcing one another, yielded infertile ground for renewing in a post-modern sense the Italian NHS. The various Reforms have not been conceived to break such a positivistic monopoly in that they did not promote cultural or educational intervention. In this context, intervention that acts at a cultural level, such as reforming university education for physicians and managers or devising immigration policies to attract adequately acculturated people to the Italian NHS, seems to be the most promising.


Overhauling oversight--European drug legislation.
At the end of next month, the European Medicines Agency (EMEA) will implement a new legislative framework and several provisions that seek to provide incentives and streamline regulatory oversight of certain monoclonal antibodies and other biologic products.


Radiolabeling of a wound-inducible pyridoxal phosphate-utilizing enzyme: evidence for its identification as ACC synthase.
1-Aminocyclopropane-1-carboxylic acid (ACC) synthase, a pyridoxal phosphate-utilizing enzyme, catalyzes the conversion of S-adenosylmethionine to ACC, the rate-limiting step in the biosynthesis of the plant hormone ethylene. We report the partial purification (400-fold) of ACC synthase from wounded pink tomato pericarp. Further purification results in a decrease in specific activity apparently due to the instability of the enzyme. Radiolabeling of a pyridoxal phosphate-utilizing protein in the ACC synthase-enriched fraction was achieved by reduction using tritiated sodium borohydride. Evidence that this radiolabeled protein is ACC synthase is presented.


Retracted: A Composite Particle Swarm Optimization Algorithm for Hospital Equipment Management Risk Control Optimization and Prediction.
[This retracts the article DOI: 10.1155/2022/5268887.].


Potential sexual function improvement by using transanal mesorectal approach for laparoscopic low rectal cancer excision.
Preliminary results of the transanal approach for low rectal cancer suggest better oncological outcomes than the conventional laparoscopic approach. We currently report the functional results. From 2008 to 2012, 100 patients with low rectal cancer and suitable for sphincter-saving resection were randomized between transanal and laparoscopic low rectal dissection. Patients derived from this randomized trial were enrolled for functional assessment. End points were bowel function (LARS bowel and Wexner continence scores) and urogenital function (IPSS, IIEF-5 and FSFI-6 scores) obtained by questionnaires sent to patients with a follow-up more than 12 months. Overall, 76 patients were eligible and 72 responded to the questionnaire: 38 in the transanal group and 34 in the laparoscopic group. The bowel function did not differ between the transanal and the laparoscopic groups: LARS 36 versus 37 (p = 0.941) and Wexner 9 versus 10 (p = 0.786). The urologic function was also similar between the two groups: IPSS 5.5 versus 3.5 (p = 0.821). Among sexually active patients before surgery, 20 of 28 (71 %) patients in the transanal group and 9 of 23 (39 %) in the laparoscopic group maintained an activity after surgery (p = 0.02). Erectile function was also better in men after transanal compared to laparoscopic low rectal dissection: IIEF 17 versus 7 (p = 0.119). Transanal approach for low rectal cancer did not change bowel and urologic functions compared to the conventional laparoscopic approach. However, there was a trend to a better erectile function with a significantly higher rate of sexual activity in the transanal group.


Permanent neonatal diabetes mellitus: prevalence and genetic diagnosis in the SEARCH for Diabetes in Youth Study.
Neonatal diabetes mellitus (NDM) is defined as diabetes with onset before 6 months of age. Nearly half of individuals with NDM are affected by permanent neonatal diabetes mellitus (PNDM). Mutations in KATP channel genes (KCNJ11, ABCC8) and the insulin gene (INS) are the most common causes of PNDM. To estimate the prevalence of PNDM among SEARCH for Diabetes in Youth (SEARCH) study participants (2001-2008) and to identify the genetic mutations causing PNDM. SEARCH is a multicenter population-based study of diabetes in youth <20 yr of age. Participants diagnosed with diabetes before 6 months of age were invited for genetic testing for mutations in the KCNJ11, ABCC8, and INS genes. Of the 15,829 SEARCH participants with diabetes, 39 were diagnosed before 6 months of age. Thirty-five of them had PNDM (0.22% of all diabetes cases in SEARCH), 3 had transient neonatal diabetes that had remitted by 18 months and 1 was unknown. The majority of them (66.7%) had a clinical diagnosis of type1 diabetes by their health care provider. Population prevalence of PNDM in youth <20 yr was estimated at 1 in 252 000. Seven participants underwent genetic testing; mutations causing PNDM were identified in five (71%), (two KCNJ11, three INS). We report the first population-based frequency of PNDM in the US based on the frequency of PNDM in SEARCH. Patients with NDM are often misclassified as having type1 diabetes. Widespread education is essential to encourage appropriate genetic testing and treatment of NDM.


Direct oral anticoagulants versus warfarin for secondary prevention of cerebral infarction and bleeding in older adults with atrial fibrillation.
Direct oral anticoagulants (DOACs) have been used for both primary and secondary prevention of cerebral infarction in older patients with atrial fibrillation (AF). However, whether DOACs are more effective and safer than warfarin for secondary prevention of cerebral infarction in older patients with AF remains unclear. Using the Japanese Diagnosis Procedure Combination database, we identified patients with AF who were hospitalized for cerebral infarction from January 1, 2015 to March 31, 2019 and were aged ≥75 years at admission. We performed propensity score-stabilized inverse probability of treatment weighting analyses to balance measured confounders between patients with AF receiving DOACs and those receiving warfarin after discharge. The primary outcomes were 365-day readmission for (a) benefit: cerebral infarction or (b) harm: bleeding events after discharge. The secondary outcomes were 365-day readmission for intracranial bleeding or gastrointestinal bleeding after discharge as well as all-cause death during readmission. Using a Fine-Gray model, we compared the subdistribution hazard ratios (SHRs) of readmission between the DOAC group and warfarin group. We identified 101,389 eligible patients, including 80,726 patients receiving DOACs and 20,663 patients receiving warfarin. After the propensity score-stabilized inverse probability of treatment weighting, the adjusted SHRs of readmission (95% confidence interval [CI]) for cerebral infarction, bleeding events, and intracranial bleeding in the DOAC group as compared with the warfarin group were 0.76 (0.71-0.81), 0.78 (0.68-0.90), and 0.69 (0.57-0.82), respectively. There was no significant difference in readmission for gastrointestinal bleeding (SHR, 1.01; 95% CI, 0.72-1.41) between the DOAC and warfarin groups. In this retrospective nationwide study, DOACs were more effective and safer than warfarin for preventing reinfarction and bleeding events in patients with AF aged ≥75 years who have a history of cerebral infarction.


Eye movements while reading an unspaced writing system: the case of Thai.
Thai has an alphabetic script with a distinctive feature - it has no spaces between words. Since previous research with spaced alphabetic systems (e.g., English) has suggested that readers use spaces to guide eye movements, it is of interest to investigate what physical factors might guide Thai readers' eye movements. Here the effects of word-initial and word-final position-specific character frequency, word-boundary bigram frequency, and overall word frequency on 30 Thai adults' eye movements when reading unspaced and spaced text was investigated. Linear mixed-effects model analyses of viewing time measures (first fixation duration, single fixation duration, and gaze duration) and of landing sites were conducted. Thai readers tended to land their first fixation at or near the centre of words, just as readers of spaced texts do. A critical determinant of this was word boundary characters: higher position-specific frequency of initial and of final characters significantly facilitated landing sites closer to the word centre while word-boundary bigram frequency appeared to behave as a proxy for initial and final position-specific character frequency. It appears, therefore, that Thai readers make use of the position-specific frequencies of word boundary characters in targeting words and directing eye movements to an optimal landing site.


Novel thermostable serine collagenase from Thermoactinomyces sp. 21E: purification and some properties.
A thermophilic actinomycete strain Thermoactinomyces sp. 21E producing a highly thermostable serine collagenase was isolated from Bulgarian soil. The collagenase, produced extracellular by Thermoactinomyces sp. 21E, was purified to homogeneity by heat treatment, ultrafiltration, saturation with ammonium sulfate and gel filtration chromatography with a 101-fold increase in specific activity and 58% recovery. The collagenase has a relative molecular mass of 50000 by SDS-PAGE. The optimum temperature for the enzyme activity was 60-65 degrees C in the absence of Ca(2+) and 70-75 degrees C in the presence of Ca(2+). About 40% of the original activity remaining after incubation at 85 degrees C for 30 min in the presence of Ca(2+). The optimum pH for the enzyme activity was 9.0-9.5 and the enzyme was stable for 1h at 70 degrees C in the pH range from 7.5 to 12.5. The collagenase was strongly inhibited by active-site inhibitors of serine protease PMSF and DFP, which indicated that the enzyme is serine protease. The enzyme activity was completely inhibited by Hg(2+), Cu(2+) and Fe(2+). However, Ca(2+ )strongly activated the collagenase activity. The collagenase from Thermoactinomyces sp. 21E showed high activity toward type I collagen, acid-soluble collagen, gelatin and Pz-PLGPR. However, elastin for collagenase was inert as substrate. The properties of the collagenase from strain 21E suggest that this enzyme is a new collagenolytic protease that differs from the collagenases and serine proteases reported so far.


Coronary artery plaque rupture and erosion: Role of wall shear stress profiling and biological patterns in acute coronary syndromes.
Wall shear stress (WSS) is involved in coronary artery plaque pathological mechanisms and modulation of gene expression. This study aims to provide a comprehensive haemodynamic and biological description of unstable (intact-fibrous-cap, IFC, and ruptured-fibrous-cap, RFC) and stable (chronic coronary syndrome, CCS) plaques and investigate any correlation between WSS and molecular pathways. We enrolled 24 CCS and 25 Non-ST Elevation Myocardial Infarction-ACS patients with IFC (n = 11) and RFC (n = 14) culprit lesions according to optical coherence tomography analysis. A real-time PCR primer array was performed on peripheral blood mononuclear cells for 17 different molecules whose expression is linked to WSS. Computational fluid dynamics simulations were performed in high-fidelity 3D-coronary artery anatomical models for three patients per group. A total of nine genes were significantly overexpressed in the unstable patients as compared to CCS patients, with no differences between IFC and RFC groups (GPX1, MMP1, MMP9, NOS3, PLA2G7, PI16, SOD1, TIMP1, and TFRC) while four displayed different levels between IFC and RFC groups (TNFα, ADAMTS13, EDN1, and LGALS8). A significantly higher WSS was observed in the RFC group (p < 0.001) compared to the two other groups. A significant correlation was observed between TNFα (p < 0.001), EDN1 (p = 0.036), and MMP9 (p = 0.005) and WSS values in the RFC group. Our data demonstrate that IFC and RFC plaques are subject to different WSS conditions and gene expressions, suggesting that WSS profiling may play an essential role in the plaque instability characterization with relevant diagnostic and therapeutic implications in the era of precision medicine.


Looking beyond the basal ganglia: the spectrum of MRI changes in methylmalonic acidaemia.
We report imaging abnormalities from 5 brain MR examinations in 4 children with methylmalonic acidaemia between the ages of 20 days and 31 months. In addition to bilateral basal ganglia lesions (pallidum) observed in 3 of 4 children, we found signs of delayed brain maturation (myelination delay, immature gyral pattern, incomplete opercularization) in all children and signs of a white matter disorder in the 3 older children. Unexpectedly, brainstem and cerebellar changes were present in all children. Reviewing the brain imaging changes reported for methylmalonic acidaemia, we discuss the findings and patterns observed in our patients. We postulate that delayed myelination and signs of a white matter disorder as well as brainstem and cerebellar involvement are common findings and may be due to a chronic neurotoxic effect on the developing and ageing brain.


Generalized Self-Doping Engineering towards Ultrathin and Large-Sized Two-Dimensional Homologous Perovskites.
Two-dimensional (2D) homologous perovskites are arousing intense interest in photovoltaics and light-emitting fields, attributing to significantly improved stability and increasing optoelectronic performance. However, investigations on 2D homologous perovskites with ultrathin thickness and large lateral dimension have been seldom reported, being mainly hindered by challenges in synthesis. A generalized self-doping directed synthesis of ultrathin 2D homologous (BA)2 (MA)n-1 Pbn Br3n+1 (1<n<∞) perovskites uses 2D (BA)2 PbBr4 perovskites as the template with MA+ dopant. Ultrathin (BA)2 (MA)n-1 Pbn Br3n+1 perovskites are formed via an intercalation-merging mechanism, with thickness shrinking down to 4.2 nm and the lateral dimension to 57 μm. The ultrathin 2D homologous (BA)2 (MA)n-1 Pbn Br3n+1 perovskites are potential materials for photodetectors with promising photoresponse and stability.


A passive physical model for DnaK chaperoning.
Almost all living organisms use protein chaperones with a view to preventing proteins from misfolding or aggregation either spontaneously or during cellular stress. This work uses a reaction-diffusion stochastic model to describe the dynamic localization of the Hsp70 chaperone DnaK in Escherichia coli cells during transient proteotoxic collapse characterized by the accumulation of insoluble proteins. In the model, misfolded ('abnormal') proteins are produced during alcoholic stress and have the propensity to aggregate with a polymerization-like kinetics. When aggregates diffuse more slowly they grow larger. According to Michaelis-Menten-type kinetics, DnaK has the propensity to bind with misfolded proteins or aggregates in order to catalyse refolding. To match experimental fluorescence microscopy data showing clusters of DnaK-GFP localized in multiple foci, the model includes spatial zones with local reduced diffusion rates to generate spontaneous assemblies of DnaK called 'foci'. Numerical simulations of our model succeed in reproducing the kinetics of DnaK localization experimentally observed. DnaK starts from foci, moves to large aggregates during acute stress, resolves those aggregates during recovery and finally returns to its initial punctate localization pattern. Finally, we compare real biological events with hypothetical repartitions of the protein aggregates or DnaK. We then notice that DnaK action is more efficient on protein aggregates than on protein homogeneously distributed.


Validation of multi-frequency bioelectrical impedance analysis versus dual-energy X-ray absorptiometry to measure body fat percentage in overweight/obese Colombian adults.
To verify the validity of multi-frequency bioelectrical impedance analysis (mBCA) for predicting body fat percentage (BF%) in overweight/obese adults using dual-energy X-ray absorptiometry (DXA) as the reference method. Forty-eight adults participated (54% women, mean age = 41.0 ± 7.3 years old). The Pearson's correlation coefficient was used to evaluate the correlation between BIA and BF% assessed by DXA. The concordance between BF% measured by both methods was obtained with Lin's concordance correlation coefficient and Bland-Altman difference plots. Measures of BF% were estimated as 39.0 (SD = 6.1) and 38.3 (SD = 6.5) using DXA and mBCA, respectively. The Pearson's correlation coefficient reflected a strong correlation (r =.921, P = .001). The paired t-test showed a significant mean difference between these methods for obese men BF% of -0.6 [(SD 1.95; 95% CI = -4.0 to 3.0), P =.037]. Overall, the bias of the mBCA was -0.6 [(SD 2.2; 95% CI = -5.0 to 3.7), P =.041], which indicated that the mBCA method significantly underestimated BF% in comparison to the reference method. Finally, in both genders, Lin's concordance correlation coefficient showed a strong agreement. More specifically the DXA value was ρc = 0.943 (95% CI = 0.775 to 0.950) and the mBCA value was ρc = 0.948 (95% CI = 0.778 to 0.978). Our analysis showed a strong agreement between the two methods as reflected in the range of BF%. These results show that mBCA and DXA are comparable methods for measuring body composition with higher body fat percentages. However, due to broad limits of agreement, we can only recommend mBCA for groups of populations.


Individual and spousal unemployment as predictors of smoking and drinking behavior.
The effects of unemployment on health behaviors, and substance use in particular, is still unclear despite substantial existing research. This study aimed to assess the effects of individual and spousal unemployment on smoking and alcohol consumption. The study was based on eight waves of geocoded Framingham Heart Study Offspring Cohort data (US) from 1971 to 2008 that contained social network information. We fit three series of models to assess whether lagged 1) unemployment, and 2) spousal unemployment predicted odds of being a current smoker or drinks consumed per week, adjusting for a range of socioeconomic and demographic covariates. Compared with employment, unemployment was associated with nearly twice the subsequent odds of smoking, and with increased cigarette consumption among male, but not female, smokers. In contrast, unemployment predicted a one drink reduction in weekly alcohol consumption, though effects varied according to intensity of consumption, and appeared stronger among women. While spousal unemployment had no effect on substance use behaviors among men, wives responded to husbands' unemployment by reducing their alcohol consumption. We conclude that individual, and among women, spousal unemployment predicted changes in substance use behaviors, and that the direction of the change was substance-dependent. Complex interactions among employment status, sex, and intensity and type of consumption appear to be at play and should be investigated further.


Diagnostic Properties of Total and Free Prostate-Specific Antigen to Predict Overall and Clinically Significant Prostate Cancer Among Men With Low Testosterone and Prior Negative Biopsy.
To evaluate whether total serum PSA, free-PSA ratio and PSA density have similar diagnostic properties for detecting prostate cancer (PCa) and clinically-significant (cs) PCa in men with normal testosterone compared to men with low testosterone with a prior negative biopsy. We conducted a retrospective analysis of 3295 men undergoing a 2-year prostate biopsy following a negative prestudy biopsy in the placebo arm of the Reduction by Dutasteride of PCa Events (REDUCE) study. Men were divided in 2 groups based on testosterone level < or ≥300 ng/dL. Diagnostic properties of total serum PSA, free-PSA ratio, and PSA density to predict PCa and csPCa, defined as Gleason score ≥7, were determined for several thresholds and plotted as receiver operator characteristic curves. A total of 603 men (18.3%) had low testosterone. The prevalence of PCa and csPCa was 92 (15.3%) and 27 (4.5%), respectively, for low testosterone men compared to 458 (17.0%) and 138 (5.1%), correspondingly, for normal testosterone men. Total PSA, free-PSA ratio and PSA density showed similar sensitivity, specificity, and accuracy to predict PCa and csPCa among low testosterone men compared to normal testosterone men. Among subjects in a clinical trial with a prior negative biopsy, total PSA, free-PSA ratio and PSA density have comparable diagnostic characteristics for PCa screening in low and normal testosterone men.


Interprofessional care of patients with type 2 diabetes mellitus in primary care: family physicians' perspectives.
There is a lack of understanding of the team processes and factors that influence teamwork and medication management practices in the care of patients with type 2 diabetes mellitus (T2DM). The purpose of the study was to explore physicians' perspectives of barriers and facilitators to interprofessional care of patients with T2DM within team-based family practice settings. This was a qualitative, descriptive study. Participants included physicians affiliated with a primary care network providing care to patients with T2DM in an interprofessional team-based primary care setting in Edmonton, Alberta, Canada. Participants' contact information was obtained from the publicly available College of Physicians and Surgeons of Alberta and respective primary care network websites. Interview questions addressed physicians' perspectives on factors or processes that facilitated and hindered the care and medication management of adult patients with T2DM in primary care team-based clinical practice. Interviews were audio-recorded, transcribed, and analyzed using qualitative content analysis and a constant comparative approach. A total of 15 family physicians participated in individual interviews. Family physicians identified facilitators of interprofessional team-based care and medication management of patients with T2DM in three theme areas-access to team members and programs, knowledgeable and skilled health professionals, and provision of patient education by other health professionals. Two themes emerged as barriers to interprofessional care - lack of provider continuity and the loss of skills from delegation of tasks. Family physicians perceive both benefits and risks to interprofessional team-based care in caring for patients with T2DM. Successful functioning of team-based care in family practice will require overcoming traditional professional roles.


Pathophysiological evaluation of pilocytic astrocytoma in adults: Histopathological and immunohistochemical analysis.
Pilocytic astrocytoma is a central nervous system tumor of slow growth, which represents 5 % of all gliomas and most often develops in the cerebellum (42-60 %), but can also arise in other neural areas, such as the optic pathway or hypothalamus (9-30 %); brainstem (9 %); spinal cord (2 %). In the pediatric population, this tumor is the second most common cause of neoplasms and, on the other hand, in adults, it is often rare, probably due to its aggressiveness in these individuals. Studies reveal that the origin of pilocytic astrocytoma is characterized by a fusion between the BRAF gene and the KIAA1549 locus, and the application of the immunohistochemistry technique for the analysis of BRAF protein expression can be a valuable tool for diagnostic purposes. Due to the relative rarity of this disease in adults, there are few publications on the most effective diagnostic and treatment strategies for this tumor. The general objective of this study was to analyze the histopathological and immunohistochemical characteristics of pilocytic astrocytoma in these patients. For this, a retrospective study of patients aged over 17 years with a diagnosis of pilocytic astrocytoma was carried out at the Department of Pathology of UNIFESP/EPM, from 1991 to 2015. In order to define BRAF positivity in the immunohistochemical analysis, at least three consecutive fields with more than 50 % immunostaining were used as criteria and, thus, it was inferred that the 7 cases analyzed were considered positive for the cytoplasmic marker BRAF V600E. Histopathological analysis associated with BRAF immunostaining is of paramount importance as a diagnostic method in these cases. However, future molecular studies will be necessary both for a better understanding of the aggressiveness and prognostic of this tumor and for research involving specific therapies for pilocytic astrocytoma in adults.


Therapeutic effect of ME1036 on endocarditis experimentally induced by methicillin-resistant Staphylococcus aureus.
The efficacy of ME1036, a novel parenteral carbapenem, was compared with that of vancomycin by using a rabbit model of methicillin-resistant Staphylococcus aureus (MRSA) endocarditis. Compared with vancomycin, ME1036 reduced the bacterial counts in the vegetations at a lower dosage or over a shorter period of administration when it was used for the treatment of MRSA endocarditis.


Aberrant CpG island methylation in cancer cell lines arises in the primary cancers from which they were derived.
A higher prevalence of epigenetic inactivation of tumor suppressor genes has been reported in cancer cell line populations compared to primary cancer populations. Cancer-related genes are commonly methylated in cancer cell lines but it is not known the extent to which tumor suppressor genes may be artificially methylated in vitro. We therefore examined 10 pancreatic cancer cell lines and corresponding primary tumors for aberrant DNA methylation of promoter CpG islands of eight genes and seven CpG islands. Using methylation-specific PCR (MSP), methylation was not detected at any of the 15 CpG islands in 15 normal pancreata or in an immortalized normal pancreatic duct epithelial (HPDE) cell line. Of 150 loci examined, 49 loci were methylated in both primary carcinomas and their corresponding cell lines, 95 loci were not methylated in either cell lines or their corresponding primary carcinomas. There were four loci methylated only in cell lines while another two loci were methylated only in primary carcinomas. Overall, the methylation status of primary carcinomas and their cell lines were concordant in 96% of cases (144 of 150) (J statistic; J=0.92, P<0.0001). We conclude that most of the DNA methylation of tumor suppressor genes observed in cancer cell lines is present in the primary carcinomas from which they were derived.


MRI for differentiating ovarian endometrioid adenocarcinoma from high-grade serous adenocarcinoma.
To investigate magnetic resonance imaging (MRI) features for differentiating ovarian endometrioid adenocarcinoma (OEC) from high-grade serous adenocarcinoma (HGSC). Twenty-three patients with 25 OECs and 93 patients with 139 HGSCs confirmed by surgery and pathology underwent conventional MRI and diffusion-weighted imaging (DWI). The MRI features of the tumors, including laterality, size, shape, configuration, signal intensity, ADC value of solid component, enhancement, ascites, synchronous primary cancer (SPC) of the ovary and endometrium, and clinical stage, were evaluated and compared between two groups. The following characteristics were significantly more common for OECs than HGSCs: unilateral (91.3% vs 50.5%, P < 0.001), larger mass (80.0% vs 48.2%, P = 0.005), round or oval shape (64.0% vs 17.3%, P < 0.001), mainly cystic with mural nodules or papillary projections (72.0% vs 18.7%, P < 0.001), cystic component with homogeneous iso- or hyperintensity on T1WI (82.6% vs 4.3%, P < 0.001), moderate enhancement (52.0% vs 26.6%, P = 0.011), no or mild ascites (91.3% vs 57.0%, P = 0.002), and SPC (43.5% vs 4.3%, P < 0.001). The ADC value of the solid component was higher in OECs (0.979 ± 0.197 × 10(-3) mm(2)/s) than in HGSCs (0.820 ± 0.112 × 10(-3) mm(2)/s) (P = 0.002). When a mainly cystic mass with mural nodules or papillary projections was associated with any one of homogeneously iso- or hyperintense cystic component on TIWI, a relatively higher ADC value and SPC, the sensitivity, specificity, accuracy, and positive and negative predictive values for characterizing OEC were 87.0%, 93.5%, 92.2%, 76.9%, and 96.7%, respectively. Conventional MRI combining DWI is helpful for differentiating OECs from HGSCs.


The gaslight phenomenon--an institutional variant.
A case of paranoid psychosis in an elderly female is reported in which recurrent episodes were apparently induced by the staff of the institution where the patient was a resident. The issues raised by this case are discussed.


Getting to Yes: Navigating the Insurance Gauntlet.
Insurance coverage of gender-affirming surgeries including facial and vocal feminization surgery remains a challenge for many patients, physicians, and practice administrators. These challenges range from disparities in coverage for commercial versus public insurance carriers, in network versus out of network benefits, preauthorization struggles, and the lack of standard coverage policies. This article aims to describe the insurance coverage and approval challenges related to facial feminization surgery and to provide guidance for surgeons and their practice administrators on how to obtain successful preauthorization/predetermination, single case agreements, and proper claim adjudication.


Circ-HMGCS1, an Indicator of Survival and Prognosis in Cervical Cancer Patients.
The aim was to investigate circ-HMGCS1 expression and its correlation with clinical features and survival in cervical cancer (CC) patients. This prospective study recruited 100 patients with CC who underwent surgical resection. Circ-HMGCS1 expression was measured by RT-qPCR. Disease-free survival (DFS) and overall survival (OS) were recorded. Circ-HMGCS1 was upregulated in tumor tissues and had a good value in separating tumor tissues from normal tissues. Circ-HMGCS1 expression in tumor tissues was positively correlated with tumor size, lymph node metastasis, and FIGO stage. High circ-HMGCS1 expression predicted worse DFS and OS. circ-HMGCS1 serves as an indicator of survival and prognosis in CC patients.


Terminal differentiation in vitro of patient-derived post-TMD megakaryoblastic AML cells.
Differentiation induction is a therapeutic principle in acute promyelocytic leukemia (AML) using all- trans retinoic acid. In cell lines with properties of AML M6/M7 (K562 and CMK), differentiation towards megakaryopoietic and erythropoietic phenotypes can be induced in vitro. Transitory myeloproliferative disorder (TMD) is a self-limited disorder of newborn infants with Down syndrome, phenotypically resembling acute myeloid leukemia of megakaryoblastic lineage. Despite spontaneous disappearance of blasts from blood and bone marrow, in about 10% of the patients, overt acute megakaryoblastic leukemia (AML M7) develops up to 4 years later. Recently, mutations of the GATA1 transcription factor have been identified in the megakaryoblastic leukemia of Down syndrome. Here, we studied cells from a patient suffering from megakaryoblastic AML at the age of 2.5 years after spontaneous remission of neonatal TMD. In vitro, terminal differentiation towards a megakaryocyte-like phenotype could be induced by phorbol myristate acetate (PMA), with typical morphological features, upregulation of platelet-specific and downregulation of erythroid antigens, going along with downregulation of c-myc. Whether spontaneous resolution of TMD is a process due to terminal differentiation is still open; however, here we give evidence that in vitro differentiation can be induced even in blasts deriving from an overt AML French-American-British (FAB) M7 after TMD.