PCA3 sensitivity and specificity for prostate cancer detection in patients with abnormal PSA and/or suspicious digital rectal examination. First Latin American experience.
Prostate Cancer Gene 3 (PCA3) is a recently described and highly specific urinary marker for prostate cancer (CaP). Its introduction in clinical practice to supplement low specificity of prostate specific antigen (PSA) can improve CaP diagnosis and follow-up. However, before its introduction, it is necessary to validate the method of PCA3 detection in distinct geographic populations. Our aim was to describe for the first time in Latin America, the application of the PROGENSA PCA3 assay for PCA3 detection in urine in Chilean men and its utility for CaP diagnosis in men with an indication of prostate biopsy. Sixty-four Chilean patients (mean age, 64 years) with indication of prostate biopsy because of elevated PSA and/or suspicious digital rectal examination (DRE) were prospectively recruited. PCA3 scores were assessed from urine samples obtained after DRE, before biopsy, and compared with PSA levels and biopsy outcome. The median PSA value and mean PCA3 score were 5.8 ng/ml and 31.7, respectively. Using a cutoff PCA3 score of 35, the sensitivity and specificity for detecting CaP were 52% and 87%, respectively. The receiver operating characteristic (ROC) curve analysis showed an area under the curve of 0.77 for PCA3 and 0.57 for PSA, for the same group of patients. In patients with previous negative biopsy, PCA3 specificity increased by 2.2%. This is the first report in Latin America on the use of PCA3 in diagnosing CaP. Our results are comparable to those reported in other populations in the literature, demonstrating the reproducibility of the test. PCA3 score was highly specific and we specially recommend its use in patients with persistent elevated PSA and prior negative biopsies.


Impact of children with complex chronic conditions on costs in a tertiary referral hospital.
To investigate the impact of complex chronic conditions on the use of healthcare resources and hospitalization costs in a pediatric ward of a public tertiary referral university hospital in Brazil. This is a longitudinal study with retrospective data collection. Overall, three one-year periods, separated by five-year intervals (2006, 2011, and 2016), were evaluated. Hospital costs were calculated in three systematic samples of 100 patients each, consisting of patients with and without complex chronic conditions in proportion to their participation in the studied year. Over the studied period, the hospital received 2,372 admissions from 2,172 patients. The proportion of hospitalized patients with complex chronic conditions increased from 13.3% in 2006 to 16.9% in 2016 as a result of a greater proportion of neurologically impaired children, which rose from 6.6% to 11.6% of the total number of patients in the same period. Patients' complexity also progressively increased, which greatly impacted the use of healthcare resources and costs, increasing by 11.6% from 2006 (R$1,300,879.20) to 2011 (R$1,452,359.71) and 9.4% from 2011 to 2016 (R$1,589,457.95). Hospitalizations of pediatric patients with complex chronic conditions increased from 2006 to 2016 in a Brazilian tertiary referral university hospital, associated with an important impact on hospital costs. Policies to reduce these costs in Brazil are greatly needed.


Oligonucleotide N3' --> P5' thio-phosphoramidate telomerase template antagonists as potential anticancer agents.
Human telomerase is a reverse transcriptase that is expressed in essentially all cancer cells, but not in the vast majority of normal somatic cells. Therefore, the specific inhibition of telomerase activity in tumors might have significant beneficial therapeutic effects. We have designed and evaluated oligonucleotide N3' --> P5' thio-phosphoramidates as telomerase template antagonists. In biochemical cell-free assays 11-13-mer thio-phosphoramidate oligonucleotides demonstrated sequence specific and dose dependent inhibition of telomerase with pico-molar IC50 values. Optimization of the oligonucleotide sequence and length resulted in the identification of a 13-mer-oligonucleotide thio-phosphoramidate GRN163 as a drug development candidate. In cell cultures GRN163 was able to inhibit telomerase activity in the absence of cationic lipid with approximately 1 microM IC50 values. Telomerase inhibition by GRN163 produced gradual telomere shortening, followed by cellular senescence and/or apoptosis of cancer derived cell lines.


Reactive organogels: self-assembled support for functional materials.
[reaction: see text] An organogel bearing reactive groups has been used as a platform for the gel-phase synthesis of more sophisticated materials. The results show that reactions take place on the gel fibers and that supramolecular aggregation modifies the product distribution in cases where several compounds can be obtained.


Transcatheter embolization of a ruptured internal pudendal artery pseudoaneurysm in a patient with neurofibromatosis type 1.
Neurofibromatosis type 1 (NF-1) is an autosomal dominant disorder. Pseudoaneurysms formation and rupture is an unusual complication of neurofibromatosis. To date, pseudoaneurysm of the internal pudendal artery associated with NF-1 has not been reported. In this article, we present a 62-yr-old man with NF-1 suffering from spontaneous hematoma of the perinea and scrotum. A digital substraction angiography disclosed a ruptured pseudoaneurysm of the right internal pudendal artery, which was successfully managed with transcatheter embolization.


Polyvictimization and externalizing symptoms in foster care children: The moderating role of executive function.
Prior research has identified the role of childhood maltreatment in externalizing problems and executive function (EF) deficits, but minimal work has been done to characterize the effects of co-occurring maltreatment types, defined as polyvictimization. Here, we sought to characterize the association between polyvictimization and externalizing problems in a sample of foster care children aged 3-4 years (N = 84) and examine how EF may mediate or moderate that relationship. A moderation model was supported in that only polyvictimized children with EF scores 1.62 or more standard deviations below the mean were at heightened risk for clinically severe externalizing problems, while no association between polyvictimization and externalizing problems were observed for children who scored at the mean or above on the EF measure. Findings highlight that EF may serve as a resilience factor indicating that individual differences in polyvictimized children's EF skills help to predict variability in externalizing problems. Future research on designing and optimizing intervention programs that target EF skills may mitigate the development of maladaptive outcomes for polyvictimized children.


[Properties of commercial licorice extracts used as a food additive].
Properties of eight commercial licorice extracts used as a food additive (sweetener, listed in the List of Existing Food Additives in the Japanese Food Sanitation Law) were surveyed. Residue on ignition ranged from 0.3 to 12.4%, and pH ranged from 4.1 to 6.8, amount of glycyrrhizin, which is the major component in licorice extract, ranged from 10.9 to 77.4%, sodium ranged from 0.1 to 1.2%, potassium ranged from 0.3 to 5.0%, and ammonium nitrogen ranged from 0.03 to 2.5%. These results indicated that various products were distributed on the market. Differences in the manufacturing process may contribute to the variations of product properties.


Modification of RNA polymerase IIO subspecies after poliovirus infection.
Infection of HeLa cells with poliovirus results in a shutdown of host transcription. In an effort to understand the mechanism(s) that underlies this process, we analyzed the distribution of RNA polymerase IIO before and after viral infection. Analysis of free and chromatin-bound enzyme indicated that there is a significant reduction in RNA polymerase IIO following infection. This observation, together with increasing evidence that transcription is catalyzed by RNA polymerase IIO, supports the hypothesis that poliovirus-induced inhibition of host transcription occurs at the level of RNA chain initiation and involves the direct modification of RNA polymerase II.


A Combination of Hemodialysis with Hemoperfusion Helped to Reduce the Cardiovascular-Related Mortality Rate after a 3-Year Follow-Up: A Pilot Study in Vietnam.
Moderate to severe hyperparathyroidism (parathyroid hormone [PTH] concentrations ≥600 pg/mL) may increase the risk of cardiovascular problems and bone disease. We assume that a combination of hemodialysis with hemoperfusion may reduce the cardiovascular-related mortality rate in maintenance hemodialysis. From 625 maintenance hemodialysis patients, 93 people met with our inclusion criteria. Based on the level of serum PTH, the patients were divided into 2 groups: 46 patients who underwent a combination of hemodialysis and hemoperfusion (HD + HP group) for consecutive 3 years and 47 patients who used hemodialysis only (HD group). During 3 years of follow-up, the ratio of mortality was 4.3% in the HD + HP group which was significantly lower than in the HD group (17%), p = 0.049. Based on Kaplan-Meier analysis of cardiovascular-related mortality, patients in the HD group (red line) exhibited a significantly higher death rate compared to the HD + HP group (violet line) (log-rank test, p = 0.049). We demonstrated that a combination of hemodialysis and hemoperfusion for 3 years helped to reduce the cardiovascular-related mortality rate.


Congenital double upper lip: review of literature and report of a case.
Congenital maxillary double lip is a rare anomaly in which a fold of redundant labial tissue becomes apparent at rest or while smiling. This might pose cosmetic or functional problems, as well as serious impact on psychological well-being, especially when it affects young children or adolescents. The treatment of choice is surgical excision. This paper presents a successfully managed case of maxillary double lip using elliptical incision under local anesthesia in a 15-year-old female patient.


Mlsa generated suppressor cells. I. Suppression is mediated by double-negative (CD3+CD5+CD4-CD8-) alpha/beta T cell receptor-bearing cells.
Grafting of cells from B10.D2 (H-2d) donors into H-2 compatible lethally irradiated (DBA/2 x B10.D2)F1 hosts results in a severe graft-vs-host reaction (GVHR), developed against DBA/2 non-H-2 Ag, with only 0 to 10% of animals surviving. This GVHR mortality rate is dramatically reduced (90 to 100% of animals survive) by donor preimmunization against Mlsa determinants. The protection against GVHR correlates with a decreased B10.D2 anti-DBA/2 proliferative response in vitro. Both in vivo and in vitro phenomena are associated with activation of CD5+ suppressor T cells in the spleens of immunized mice. The present work was designed to study the origin of these suppressor cells and to further characterize their phenotype. The results show that significant suppression is not inducible in "B" mice. In contrast, in mice that were only thymectomized or else pretreated in vivo with anti-CD4 or anti-CD8 mAb, the suppressor cells are activated as efficiently as in normal mice. The suppression of GVHR mortality and proliferative responses in vitro is lost after depletion from preimmunized splenocytes of CD5+ T cells and remains unaltered after depletion of CD4+ or CD8+ T cells or both. Depletion of asialo GM1+ cells removes all NK activity, whereas the suppression is decreased only slightly. FACS analysis showed that double-negative (DN) cells from normal and immunized mice contain both CD3+ and CD3- cells; the vast majority of the CD3+ DN T cells express the alpha/beta T cell receptor. Suppression of GVHR and of proliferative responses in vitro are abrogated after elimination of CD3+ cells. These results suggest that Mlsa generated suppressor cells: 1) are derived from post-thymic long-lived T cell precursors; 2) are low asialo GM-1+ but do not exhibit NK activity; 3) belong to a subset of peripheral CD5+ DN T cells bearing a CD3-associated alpha/beta-heterodimer.


Persistent NKH with transient or absent symptoms and a homozygous GLDC mutation.
Three of four nonketotic hyperglycinemia patients homozygous for a novel GLDC mutation (A802V) were treated by assisted respiration and/or sodium benzoate with or without ketamine and had transient neonatal or absent symptoms and normal developmental outcome, despite persisting biochemical evidence of nonketotic hyperglycinemia. This exceptional outcome may be related to the high residual activity of the mutant protein (32% of wild type) and therapeutic intervention during a critical period of heightened brain exposure and sensitivity to glycine.


Correlating the para-Substituent Effects on Ru(II)-Polypyridine Photophysical Properties and on the Corresponding Hybrid P450 BM3 Enzymes Photocatalytic Activity.
Ru(II)-diimine complexes covalently attached near the heme active site of P450 BM3 enzymes have been used to rapidly inject electrons and drive selective C-H functionalization upon visible light irradiation. Herein, we have generated a series of hybrid P450 BM3 enzymes containing a photosensitizer of general formula [Ru(4,4'-X2bpy)2(PhenA)]2+ where X = Cl, H, tBu, Me OPhe, OMe, or NMe2, bpy = 2,2'-bipyridine, and PhenA = 5-acetamido-1,10-phenanthroline. We then probed the effect of electron-withdrawing and -donating groups at the para position of the 4,4'-X2bpy ligands on the corresponding hybrid enzymes photocatalytic activity. A 3-fold improvement in initial reaction rate was noted when varying the substituent from Cl to tBu, however, the reaction rates decrease thereafter with the more electron donating groups. In order to rationalize those effects, we investigated the variation of the substituent on the photophysical properties of the corresponding [Ru(4,4'-X2bpy)2(bpy)]2+ model complexes. Several linear correlations were established between the E(III/II) potential, the MLCT emission, and absorption energies as well as the logarithm of the luminescence quenching rate vs the summative Brown-Okamoto parameter (Σσp+). Moreover, a downward curved Hammett plot is observed with the hybrid enzyme initial reaction rate revealing mechanistic details about the overall light-driven enzymatic process.


[An evaluation of the epidemiological and immunological efficacy of the vaccinal prophylaxis of diphtheria and tetanus].
The extensive use of adsorbed diphtheria-tetanus toxoid with reduced antigen content was found to be ineffective in the prophylaxis of diphtheria: 86.3% of diphtheria patients among those who had been immunized with this preparation fell only a year after the first booster immunization, and the proportion of those who proved to be unprotected against diphtheria on years 3, 4 and 5 after immunization reached, respectively, 21.0%, 35.5% and 49.4%. The number of children immunized with this preparation at common preschool institutions may reach 50% and more, and with an increase in the coverage of children with immunization from 10% to 50% the proportion of unprotected children may rise from 7.4% to 17.8%. The proportion of preschool institutions, insufficiently protected from diphtheria and, as a consequence, running a considerable risk of becoming (in case of the penetration of this infection) the foci of diphtheria, was found to reach 32.9%.


Prevalence of Guillain-Barré syndrome among Zika virus infected cases: a systematic review and meta-analysis.
Zika virus (ZIKV) is an emergent flavivirus transmitted mainly through Aedes spp. mosquitoes that is posing challenge to healthcare services in countries experiencing an outbreak. Usually ZIKV infection is mild, but in some cases it has been reported to progress into neurological diseases such as microcephaly in infants and Guillain-Barré syndrome (GBS) in adults. GBS is a debilitating autoimmune disorder that affects peripheral nerves. Since ZIKV caused massive outbreaks in South America in the past few years, we aimed to systematically review the literature and perform a meta-analysis to estimate the prevalence of GBS among ZIKV-infected individuals. We searched PubMed and Cochrane databases and selected three studies for a meta-analysis. We estimated the prevalence of ZIKV-associated GBS to be 1.23% (95% CI=1.17-1.29%). Limitations include paucity of data regarding previous flavivirus infections and ZIKV-infection confirmation issues. Our estimate seems to be low, but cannot be ignored, since ZIKV outbreaks affects an overwhelming number of individuals and GBS is a life-threatening debilitating condition, especially in pregnant women. ZIKV infection cases must be closely followed to assure prompt care to reduce the impact of GBS associated-sequelae on the quality of life of those affected.


Management of Persistent Air Leaks with Intrabronchial Valves.
Persistent air leaks (PALs) are regarded as a frequent complication after thoracic surgery resulting in prolonged hospitalization and increased morbidity. Several more or less invasive therapeutic approaches are available for treatment of PAL with varying degrees of success. The endoscopic placement of one-way intrabronchial valves in the segment(s) in which the air leak has been located offers a highly effective and well-tolerated minimal invasive option for patients with PAL.


Preparation of Carbon-Rich g-C3 N4 Nanosheets with Enhanced Visible Light Utilization for Efficient Photocatalytic Hydrogen Production.
Exfoliation of layered bulk g-C3 N4 (CNB) to thin g-C3 N4 sheets in nanodomains has attracted much attention in photocatalysis because of the intriguing properties of nanoscaled g-C3 N4 . This study shows that carbon-rich g-C3 N4 nanosheets (CNSC) can be easily prepared by self-modification of polymeric melon units through successively thermally treating bulk g-C3 N4 in an air and N2 atmosphere. The prepared CNSC not only retain the outstanding properties of nanosheets, such as large surface area, high aspect ratios, and short charges diffusion distance, but also overcome the drawback of enlarged bandgap caused by the quantum size effect, resulting in an enhanced utilization of visible light and photoinduced electron delocalization ability. Therefore, the as-prepared CNSC show a high hydrogen evolution rate of 39.6 µmol h-1 with a turnover number of 24.98 in 1 h at λ > 400 nm. Under irradiation by longer wavelength of light (λ > 420 nm), CNSC still exhibit a superior hydrogen evolution rate, which is 72.9 and 5.4 times higher than that of bulk g-C3 N4 and g-C3 N4 nanosheets, respectively.


Nephrotic syndrome and aberrant expression of laminin isoforms in glomerular basement membranes for an infant with Herlitz junctional epidermolysis bullosa.
Herlitz junctional epidermolysis bullosa (H-JEB) is a hereditary bullous disease caused by absent expression of laminin-5, a component of anchoring filaments within the dermal-epidermal basement membrane zone. Affected individuals usually die during the first 1 year of life. We studied an infant with H-JEB who presented with nephrotic syndrome, a previously unreported complication that may contribute to early death in this disease. DNA analysis revealed a compound heterozygote for mutations 2379delG and Q995X in the LAMB3 gene. The patient had massive albuminuria, attributable to failure of the glomerular filtration barrier, and high urinary N-acetylglucosaminidase levels, indicating renal tubular involvement. Electron-microscopic examination of the renal tissue revealed diffuse fusion of the foot processes, irregular swelling of the lamina rara interna, and disappearance of endothelial cell fenestrations. Immunohistopathologic analysis of the patient's renal tissue revealed compositional changes in laminin isoforms of the glomerular basement membrane and no detectable laminin-5 in the renal tubular basement membrane, which suggests that laminin-5 may play an important role in renal function. Our findings strongly suggest that H-JEB should be considered in the spectrum of congenital nephrotic syndromes. Combination therapy with meticulous skin care and treatment strategies established for congenital nephrotic syndromes may rescue patients with this disease.


Absolute quantification and characterization of oxylipins in lupus nephritis and systemic lupus erythematosus.
Systemic lupus erythematosus (SLE) is a chronic autoimmune disease with multi-organ inflammation and defect, which is linked to many molecule mediators. Oxylipins as a class of lipid mediator have not been broadly investigated in SLE. Here, we applied targeted mass spectrometry analysis to screen the alteration of oxylipins in serum of 98 SLE patients and 106 healthy controls. The correlation of oxylipins to lupus nephritis (LN) and SLE disease activity, and the biomarkers for SLE classification, were analyzed. Among 128 oxylipins analyzed, 92 were absolutely quantified and 26 were significantly changed. They were mainly generated from the metabolism of several polyunsaturated fatty acids, including arachidonic acid (AA), linoleic acid (LA), docosahexanoic acid (DHA), eicosapentanoic acid (EPA) and dihomo-γ-linolenic acid (DGLA). Several oxylipins, especially those produced from AA, showed different abundance between patients with and without lupus nephritis (LN). The DGLA metabolic activity and DGLA generated PGE1, were significantly associated with SLE disease activity. Random forest-based machine learning identified a 5-oxylipin combination as potential biomarker for SLE classification with high accuracy. Seven individual oxylipin biomarkers were also identified with good performance in distinguishing SLE patients from healthy controls (individual AUC > 0.7). Interestingly, the biomarkers for differentiating SLE patients from healthy controls are distinct from the oxylipins differentially expressed in LN patients vs. non-LN patients. This study provides possibilities for the understanding of SLE characteristics and the development of new tools for SLE classification.


Enabling Highly-Reversible Aqueous Zn-Ion Batteries via 4-Hydroxybenzoic Acid Sodium Salt Electrolyte Additive.
Due to the intrinsic safety and cost effectiveness, aqueous Zn-ion batteries (AZIBs) are considered a promising candidate for future energy storage systems. However, the widespread implementation of AZIBs faces significant obstacles due to various undesirable side reactions, including hydrogen evolution reaction (HER), corrosion, and uncontrolled dendrite growth at the anodes. Here, 4-hydroxybenzoic acid sodium salt (PHB) is employed in the ZnSO4 electrolyte to enable highly-reversible zinc anodes. PHB has a greater tendency to bind with the Zn surface, resulting in increased steric effects within the electrolyte. As a result, it hinders the direct interaction between anode and water while facilitating the uniform plating of Zn2+ . Zn/Zn batteries with PHB additives realized more than 1600 h stable cycling life under 1 mA cm-2 and 1 mAh cm-2 . Moreover, Zn/Cu batteries with PHB additives achieved a reversible plating/stripping process for over 500 cycles with high average CE of 98.6 %. In addition, the assembled Zn/NH4 V4 O10 batteries with PHB additive yielded 80.5 mAh g-1 after 1000 cycles at 10 A g-1 . The inexpensive and effective application of PHB as an electrolyte additive has the potential to significantly enhance the stability and dependability of ZIBs.


Problem gambling inside and out: the assessment of community and institutional problem gambling in the Canadian correctional system.
This paper reports on the results of a multi-site survey of gambling behaviour and gambling problems amongst offenders in correctional institutions in Ontario, Canada, conducted between 2008 and 2011. A total of 422 (completion rate 61.5 %) incarcerated offenders (381 male and 41 female) took part in the study including 301 federal offenders and 121 provincial offenders. Based on the Problem Gambling Severity Index of the Canadian Problem Gambling Index (CPGI/PGSI) the prevalence rate of severe problem gambling was 8.9 prior to incarceration and 4.4 % during incarceration. These numbers are substantially higher than rates found among the general public. Thirty-four percent of the sample reported gambling in prison. Half of those who suffered from gambling problems before incarceration continued to have gambling problems during incarceration. People with problems related to slot machines prior to incarceration reported fewer gambling problems during incarceration compared to other problem gamblers.


[Contribution and Cost-Effectiveness of ABR and MRI in Acoustic Neuroma screening. Retrospective Study of 151 Cases].
The aim of this study was to retrospectively assess during two periods (1991-1995 and 1996-2000) if MRI spreading had changed: (1) private ENT physicians screening habits; (2) the average tumor size at the time of diagnosis and the diagnostic delay of acoustic neuroma; and (3) the cost of acoustic neuroma diagnosis. In addition, the sensibility of each diagnostic test was calculated on 151 tumors. Our results show no significant change neither in the screening strategy (except a mild decrease in CT-scan utilization) nor in the tumor size, diagnostic delay or diagnostic cost between the two periods. Even if MRI is the gold standard for acoustic neuroma diagnosis, our 86%-sensibility of ABR, increased to 99% if combined with stapedial reflex and caloric test may still incline to use ABR in selected cases.


Effects of cholesterol transport inhibitor U18666A on APP metabolism in rat primary astrocytes.
Amyloid β (Aβ) peptides generated from the amyloid precursor protein (APP) play an important role in the degeneration of neurons and development of Alzheimer's disease (AD). Current evidence indicates that high levels of cholesterol-which increase the risk of developing AD-can influence Aβ production in neurons. However, it remains unclear how altered level/subcellular distribution of cholesterol in astrocytes can influence APP metabolism. In this study, we evaluated the effects of cholesterol transport inhibitor U18666A-a class II amphiphile that triggers redistribution of cholesterol within the endosomal-lysosomal (EL) system-on APP levels and metabolism in rat primary cultured astrocytes. Our results revealed that U18666A increased the levels of the APP holoprotein and its cleaved products (α-/β-/η-CTFs) in cultured astrocytes, without altering the total levels of cholesterol or cell viability. The cellular levels of Aβ1-40 were also found to be markedly increased, while secretory levels of Aβ1-40 were decreased in U18666A-treated astrocytes. We further report a corresponding increase in the activity of the enzymes regulating APP processing, such as α-secretase, β-secretase, and γ-secretase as a consequence of U18666A treatment. Additionally, APP-cleaved products are partly accumulated in the lysosomes following cholesterol sequestration within EL system possibly due to decreased clearance. Interestingly, serum delipidation attenuated enhanced levels of APP and its cleaved products following U18666A treatment. Collectively, these results suggest that cholesterol sequestration within the EL system in astrocytes can influence APP metabolism and the accumulation of APP-cleaved products including Aβ peptides, which can contribute to the development of AD pathology.


Involuntary motion tracking for medical dynamic infrared thermography using a template-based algorithm.
In medical applications, Dynamic Infrared (IR) Thermography is used to detect the temporal variation of the skin temperature. Dynamic Infrared Imaging first introduces a thermal challenge such as cooling on the human skin, and then a sequence of hundreds of consecutive frames is acquired after the removal of the thermal challenge. As a result, by analyzing the temporal variation of the skin temperature over the image sequence, the thermal signature of skin abnormality can be examined. However, during the acquisition of dynamic IR imaging, the involuntary movements of patients are unavoidable, and such movements will undermine the accuracy of diagnosis. In this study, based on the template-based algorithm, a tracking approach is proposed to compensate the motion artifact. The affine warping model is adopted to estimate the motion parameter of the image template, and then the Lucas-Kanade algorithm is applied to search for the optimized parameters of the warping function. In addition, the weighting mask is also incorporated in the computation to ensure the robustness of the algorithm. To evaluate the performance of the approach, two sets of IR image sequences of a subject's hand are analyzed: the steady-state image sequence, in which the skin temperature is in equilibrium with the environment, and the thermal recovery image sequence, which is acquired after cooling is applied on the skin for 60 seconds. By selecting the target region in the first frame as the template, satisfactory tracking results were obtained in both experimental trials, and the robustness of the approach can be effectively ensured in the recovery trial.


Adhesive dynamics.
Adhesive dynamics (AD) is a method for simulating the dynamic response of biological systems in response to force. Biological bonds are mechanical entities that exert force under strain, and applying forces to biological bonds modulates their rate of dissociation. Since small numbers of events usually control biological interactions, we developed a simple method for sampling probability distributions for the formation or failure of individual bonds. This method allows a simple coupling between force and strain and kinetics, while capturing the stochastic response of biological systems. Biological bonds are dynamically reconfigured in response to applied mechanical stresses, and a detailed spatio-temporal map of molecules and the forces they exert emerges from AD. The shape or motion of materials bearing the molecules is easily calculated from a mechanical energy balance provided the rheology of the material is known. AD was originally used to simulate the dynamics of adhesion of leukocytes under flow, but new advances have allowed the method to be extended to many other applications, including but not limited to the binding of viruses to surface, the clustering of adhesion molecules driven by stiff substrates, and the effect of cell-cell interaction on cell capture and rolling dynamics. The technique has also been applied to applications outside of biology. A particular exciting recent development is the combination of signaling with AD (so-called integrated signaling adhesive dynamics, or ISAD), which allows facile integration of signaling networks with mechanical models of cell adhesion and motility. Potential opportunities in applying AD are summarized.


In vivo modification of adriamycin-induced apoptosis in L-5178Y lymphoma cell-bearing mice by (+)-alpha-tocopherol and superoxide dismutase.
Apoptosis was followed in L5178Y lymphoma cell-bearing mice at different times after intraperitoneal injections of adriamycin (ADM). Apoptosis was determined morphologically and confirmed by DNA laddering on electrophoresis. Apoptosis was observed 36h after injection of 5mg/kg ADM (apoptotic cell index 64.2+/-5.6 vs. 1.5+/-2.1 from the untreated group) and confirmed by DNA electrophoresis. However, when the animals were pretreated with (+)-alpha-tocopherol acid succinate or superoxide dismutase before ADM administration apoptotic index significantly diminished (P<0.05) and the DNA electrophoresis did not show fragmentations. We conclude that in ADM-treated mice, tumour cell death occurs in two ways: first by necrosis, then later by apoptosis. These observations are likely to be associated with or caused by the generation of reactive oxygen species.


Biochemical, molecular, and functional characterization of porin isoforms from potato mitochondria.
The mitochondrial outer membrane of eukaryotic cells contains a voltage-dependent anion channel termed porin. In the organisms studied so far only one type of porin has been identified at the protein level. Here we present a biochemical and molecular genetic analysis of two different porin polypeptides of M(r) 34,000 and 36,000 from the outer membranes of potato mitochondria (termed POM 34 and POM 36, respectively). N-terminal sequencing and the use of labeled oligonucleotide mixtures derived from these amino acid sequences allowed the isolation of cDNA clones encoding the 34- and 36-kDa proteins. They have similar steady state protein levels and share about 75% identical amino acids suggesting that they represent isoforms. In addition, a third cDNA clone coding for a slightly different isoform of the 36-kDa protein was characterized. The polypeptides encoded by the three cDNA clones share the highest degree of sequence identity with mitochondrial porins from fungi and mammals. Tentative models of the secondary structure of the 34- and 36-kDa proteins suggest the occurrence of a 16-stranded beta-barrel typical for bacterial and mitochondrial porins. Purification of the 34-kDa protein by hydroxyapatite chromatography allowed conductance measurements in artificial bilayers. The 34-kDa protein is a voltage-dependent, channel-forming component with single channel conductances of 3.5 and 2.0 nanosiemens in 1 M KCl. In spite of the striking functional similarities to mitochondrial porins from other organisms neither the 34- nor the 36-kDa proteins are able to complement the respiratory defect of a yeast por- mutant.


Does socioeconomic status matter? A meta-analysis on parent training effectiveness for disruptive child behavior.
Disadvantaged family socioeconomic status (SES) is often assumed to diminish parent training program effectiveness. In examining effects of SES, influences of initial problem severity have been largely ignored. In the present meta-analysis, we examined (a) whether there is a differential influence of SES on parent training effectiveness at immediate posttreatment and at 1-year follow-up-controlling for levels of initial problem severity--and (b) whether SES interacts with initial problem severity in its effect on program effectiveness. Seventy-five studies on parent training program effectiveness to reduce disruptive child behavior were included. Separate analyses were conducted for immediate posttreatment and approximately 1-year follow-up assessments. Immediately posttreatment, disadvantaged samples benefited less from parent training, but only when they had low levels of initial problem severity. At follow-up, disadvantaged samples benefited less from parent training regardless of initial problem severity. Initial problem severity was a strong predictor of effect sizes both immediately posttreatment and at follow-up. Parent training programs are equally effective for disadvantaged and nondisadvantaged families immediately posttreatment, at least when initial problems are severe. Maintenance of treatment gain, however, seems harder for disadvantaged families, suggesting that more sustained family support may be needed.


Periodic limb movements during sleep are associated with poor health-related quality of life in patients with obstructive sleep apnea.
The clinical significance of the comorbidity of periodic limb movements during sleep (PLMS) in sleep-disordered breathing remains unclear. This study aimed to determine whether or not the presence of PLMS is related to depressed mood and poor quality of life in subjects with obstructive sleep apnea (OSA). We defined PLMS as a periodic leg movement index of > 15/h. Scores for the Medical Outcomes Study Short Form Health Survey and Beck Depression Inventory were assessed with multiple logistic or linear regression analyses. Of 1370 subjects with OSA, a prevalence of PLMS was 14.1%. Older age, men, and obesity were positively associated with PLMS. PLMS occurred in 17%, 15%, and 12% of mild, moderate, and severe subjects with OSA, respectively. Severe OSA was less likely to be associated with PLMS than mild OSA. PLMS negatively correlated with physical and mental component summary scores of the health survey but not with Beck Depression Inventory scores after controlling for confounding variables. PLMS were significantly associated with poor sleep architecture on polysomnography. However, the relationship between PLMS and disturbed sleep was no longer significant after adjusting for age. Health-related quality of life, including physical and mental health but not depressive symptoms, was worse in subjects with OSA and PLMS than in those without PLMS.


Clearance and beyond: the complementary roles of GFR measurement and injury biomarkers in acute kidney injury (AKI).
Acute kidney injury (AKI) is a common and frequently fatal illness in critically ill patients. The reliance on daily measurements of serum creatinine as a surrogate of glomerular filtration rate (GFR) not only delays diagnosis and development of successful therapies but also hinders insight into the pathophysiology of human AKI. Measurement of GFR under non-steady-state conditions remains an elusive gold standard against which biomarkers of renal injury need to be judged. Approaches to the rapid (near real-time) measurement of GFR are explored. Even if real-time GFR was available, absent baseline information will always limit diagnosis of AKI based on GFR or serum creatinine to a detection of change. Biomarkers of renal cellular injury have provided new strategies to facilitate detection and early intervention in AKI. However, the diagnostic and predictive performance of urinary biomarkers of injury vary, depending on both the time after renal injury and on the preinjury GFR. Progress in understanding the role of each novel biomarker in the causal pathways of AKI promises to enhance their diagnostic potential. We predict that combining rapid measures of GFR with biomarkers of renal injury will yield substantive progress in the treatment of AKI.


Selective and sensitive aqueous-phase detection of 2,4,6-trinitrophenol (TNP) by an amine-functionalized metal-organic framework.
Highly selective and sensitive aqueous-phase detection of nitro explosive 2,4,6-trinitrophenol (TNP) by a hydrolytically stable 3D luminescent metal-organic framework is reported. The compound senses TNP exclusively even in the presence of other nitro-compounds, with an unprecedented sensitivity in the MOF regime by means of strategic deployment of its free amine groups. Such an accurate sensing of TNP, widely recognized as a harmful environmental contaminant in water media, establishes this new strategic approach as one of the frontiers to tackle present-day security and health concerns in a real-time scenario.


Mutations in GFPT1-related congenital myasthenic syndromes are associated with synaptic morphological defects and underlie a tubular aggregate myopathy with synaptopathy.
Mutations in GFPT1 (glutamine-fructose-6-phosphate transaminase 1), a gene encoding an enzyme involved in glycosylation of ubiquitous proteins, cause a limb-girdle congenital myasthenic syndrome (LG-CMS) with tubular aggregates (TAs) characterized predominantly by affection of the proximal skeletal muscles and presence of highly organized and remodeled sarcoplasmic tubules in patients' muscle biopsies. We report here the first long-term clinical follow-up of 11 French individuals suffering from LG-CMS with TAs due to GFPT1 mutations, of which nine are new. Our retrospective clinical evaluation stresses an evolution toward a myopathic weakness that occurs concomitantly to ineffectiveness of usual CMS treatments. Analysis of neuromuscular biopsies from three unrelated individuals demonstrates that the maintenance of neuromuscular junctions (NMJs) is dramatically impaired with loss of post-synaptic junctional folds and evidence of denervation-reinnervation processes affecting the three main NMJ components. Moreover, molecular analyses of the human muscle biopsies confirm glycosylation defects of proteins with reduced O-glycosylation and show reduced sialylation of transmembrane proteins in extra-junctional area. Altogether, these results pave the way for understanding the etiology of this rare neuromuscular disorder that may be considered as a "tubular aggregates myopathy with synaptopathy".


Delivery of benzoporphyrin derivative, a photosensitizer, into atherosclerotic plaque of Watanabe heritable hyperlipidemic rabbits and balloon-injured New Zealand rabbits.
In this study we compared the plasma distribution and arterial accumulation of a photosensitizer, benzoporphyrin derivative (BPD), in two models of atherosclerosis: the spontaneous lesions of the Watanabe heritable hyperlipidemic (WHHL) rabbit and induced lesions of the balloon-injured, cholesterol-fed New Zealand white (NZW) rabbit. Selective uptake and retention of a photosensitizer by the abnormal portion of a vessel is a necessity in order for photodynamic therapy to become a successful modality for inhibition of intimal hyperplasia, selective removal of atherosclerotic tissue or imaging of diseased arteries. Liposome-based formulations were compared to freshly isolated native low density lipoprotein (LDL) and acetylated-LDL (Ac-LDL) as delivery vehicles for BPD. Plasma distribution of the photosensitizer was analyzed by KBr density gradient ultracentrifugation. Although the delivery vehicle influenced plasma distribution immediately postinjection, BPD subsequently partitioned according to the plasma concentration of the lipoproteins. Photosensitizer level in plaque and normal artery specimens was determined by ethyl acetate extraction and spectrofluorometric measurement. The measurement of BPD in normal and atherosclerotic arterial tissue demonstrated a selective accumulation in atherosclerotic tissue. Preassociation with LDL and Ac-LDL enhanced accumulation of BPD in atherosclerotic tissue when compared with normal artery (mean ratios of 2.8 and 4.1 were achieved, respectively). These results indicate that the preferential uptake of BPD by atherosclerotic plaque can be enhanced by preassociation with plasma lipoproteins, suggesting that light activation could lead to a highly selective destruction of diseased vascular tissue.


Drosophila melanogaster - an embryonic model for studying behavioral and biochemical effects of manganese exposure.
Embryonic animals are especially susceptible to metal exposure. Manganese (Mn) is an essential element, but in excess it can induce toxicity. In this study we used Drosophila melanogaster as an embryonic model to investigate biochemical and behavioral alterations due to Mn exposure. Flies were treated with standard medium supplemented with MnCl2 at 0.1 mM, 0.5 mM or 1 mM from the egg to the adult stage. At 0.5 mM and 1 mM Mn, newly ecloded flies showed significantly enhanced locomotor activity when assessed by negative geotaxis behavior. In addition, a significant increase in Mn levels (p < 0.0001) was observed, while Ca, Fe, Cu, Zn and S levels were significantly decreased. A significant drop in cell viability occurred in flies exposed to 1 mM Mn. There was also an induction of reactive oxygen species at 0.5 mM and 1 mM Mn (p < 0.05). At 1 mM, Mn increased Catalase (p < 0.005), Superoxide Dismutase (p < 0.005) and Hsp83 (p < 0.0001) mRNA expression, without altering Catalase or Superoxide Dismutase activity; the activity of Thioredoxin reductase and Glutatione-S-transferase enzymes was increased. Mn treatment did not alter ERK or JNK1/2 phosphorylation, but at 1 mM caused an inhibition of p38(MAPK) phosphorylation. Together these data suggest mechanisms of adaptation in the fly response to Mn exposure in embryonic life.


Versatile four-leg thermoelectric module test setup adapted to a commercial sample holder system for high temperatures and controlled atmospheres.
A high temperature thermoelectric test setup for the NORECS ProboStat™ sample holder cell has been designed, constructed, and tested. It holds four thermoelectric legs of up to 5 × 5 mm2 area each and flexible height, allows various interconnects to be tested, and utilizes the spring-load system of the ProboStat for fixation and contact. A custom stainless steel support tube flushed with water provides the cold sink, enabling large temperature gradients. Thermocouples and electrodes as well as the gas supply and outer tube use standard ProboStat base unit feedthroughs and dimensions. The setup allows for testing in controlled atmospheres with the hot side temperature of up to around 1000 °C and a temperature gradient of up to 600 °C. We demonstrate the test setup on a four-leg Li-NiO/Al-ZnO module with gold interconnects. The comparison between the predicted performance based on individual material parameters and the experimentally obtained module performance underlines the necessity for testing materials in combination, including interconnects. The four-leg setup allows versatile match-screening, performance evaluation, and long-term stability studies of thermoelectric materials in combination with hot and cold side interconnects under realistic operational conditions.


[Oral carcinoma: From awareness to survivorship].
Oral and oropharyngeal cancer is amongst the most common and fatal malignant diseases worldwide, with oral squamous cell carcinomas constitute more than 90% of all lesions. This article follows the oral cancer patient from the point of view of the oral medicine practitioner; from the stage of the potentially malignant disorders to the diagnosis of cancer, to the management of short-term comlications of the cancer therapy, to the stage of long-term follow up and management of lifelong oral complications of the oncologic treatment.


Natural Morin-Based Metal Organic Framework Nanoenzymes Modulate Articular Cavity Microenvironment to Alleviate Osteoarthritis.
Osteoarthritis (OA) is always characterized as excessive reactive oxygen species (ROS) inside articular cavity. Mimicking natural metalloenzymes with metal ions as the active centers, stable metal organic framework (MOF) formed by natural polyphenols and metal ions shows great potential in alleviating inflammatory diseases. Herein, a series of novel copper-morin-based MOF (CuMHs) with different molar ratios of Cu2+ and MH were employed to serve as ROS scavengers for OA therapy. As a result, CuMHs exhibited enhanced dispersion in aqueous solution, improved biocompatibility, and efficient ROS-scavenging ability compared to MH. On the basis of H2O2-stimulated chondrocytes, intracellular ROS levels were efficiently declined and cell death was prevented after treated by Cu6MH (Cu2+ and MH molar ratio of 6:1). Meanwhile, Cu6MH also exhibited efficient antioxidant and anti-inflammation function by down-regulating the expression of IL6, MMP13, and MMP3, and up-regulating cartilage specific gene expression as well. Importantly, Cu6MH could repair mitochondrial function by increasing mitochondrial membrane potential, reducing the accumulation of calcium ions, as well as promoting ATP content production. In OA joint model, intra-articular (IA) injected Cu6MH suppressed the progression of OA. It endowed that Cu6MH might be promising nanoenzymes for the prevention and treatment of various inflammatory diseases.


Comment on "Writhe formulas and antipodal points in plectonemic DNA configurations".
We point out that the disagreement between the paper by Neukirch and Starostin [S. Neukirch and E. L. Starostin, Phys. Rev. E 78, 041912 (2008)] and ours [J. Samuel, S. Sinha, and A. Ghosh, J. Phys.: Condens. Matter 18, S253 (2006)] is only apparent and stems from a difference in approach. Neukirch and Starostin are concerned with classical elasticity and individual curves while we focus on statistical averages over curves.


Cytokine storm intervention in the early stages of COVID-19 pneumonia.
Clinical intervention in patients with corona virus disease 2019 (COVID-19) has demonstrated a strong upregulation of cytokine production in patients who are critically ill with SARS-CoV2-induced pneumonia. In a retrospective study of 41 patients with COVID-19, most patients with SARS-CoV-2 infection developed mild symptoms, whereas some patients later developed aggravated disease symptoms, and eventually passed away because of multiple organ dysfunction syndrome (MODS), as a consequence of a severe cytokine storm. Guidelines for the diagnosis and treatment of SARS-CoV-2 infected pneumonia were first published January 30th, 2020; these guidelines recommended for the first time that cytokine monitoring should be applied in severely ill patients to reduce pneumonia related mortality. The cytokine storm observed in COVID-19 illness is also an important component of mortality in other viral diseases, including SARS, MERS and influenza. In view of the severe morbidity and mortality of COVID-19 pneumonia, we review the current understanding of treatment of human coronavirus infections from the perspective of a dysregulated cytokine and immune response.


Promising Cell Configuration for Next-Generation Energy Storage: Li2S/Graphite Battery Enabled by a Solvate Ionic Liquid Electrolyte.
Lithium-ion sulfur batteries with a [graphite|solvate ionic liquid electrolyte|lithium sulfide (Li2S)] structure are developed to realize high performance batteries without the issue of lithium anode. Li2S has recently emerged as a promising cathode material, due to its high theoretical specific capacity of 1166 mAh/g and its great potential in the development of lithium-ion sulfur batteries with a lithium-free anode such as graphite. Unfortunately, the electrochemical Li(+) intercalation/deintercalation in graphite is highly electrolyte-selective: whereas the process works well in the carbonate electrolytes inherited from Li-ion batteries, it cannot take place in the ether electrolytes commonly used for Li-S batteries, because the cointercalation of the solvent destroys the crystalline structure of graphite. Thus, only very few studies have focused on graphite-based Li-S full cells. In this work, simple graphite-based Li-S full cells were fabricated employing electrolytes beyond the conventional carbonates, in combination with highly loaded Li2S/graphene composite cathodes (Li2S loading: 2.2 mg/cm(2)). In particular, solvate ionic liquids can act as a single-phase electrolyte simultaneously compatible with both the Li2S cathode and the graphite anode and can further improve the battery performance by suppressing the shuttle effect. Consequently, these lithium-ion sulfur batteries show a stable and reversible charge-discharge behavior, along with a very high Coulombic efficiency.


Why do many NMDA antagonists fail, while others are safe and effective at blocking excitotoxicity associated with dementia and acute injury?
Similar to drug development programs for stroke and traumatic brain injury, programs developed for Alzheimer's disease (AD) have not been very effective in treating dementia. Recently, researchers have explored modulating excitatory synaptic neurotransmission via the N-methyl-D-aspartate receptor (NMDAR) to treat AD. However, many investigators doubt that NMDA antagonists are safe and effective for treating persons with AD because they have failed in stroke and trauma programs. This article explores the role of NMDA-mediated excitotoxicity in AD, reviews how the NMDAR functions, highlights the side effects and alternate signaling pathways that are initiated from NMDAR activation, provides examples of NMDA antagonists that do not exhibit the typical side effects, and discusses why some NMDA antagonist compounds are effective and safe in limiting cascades of excitotoxicity in dementia or acute brain injury.


Differential therapeutics and the impaired physician: patient-treatment matching by specificity and intensity.
The objective of this study was to determine the nature and degree of patient to treatment matching for a sample of physicians based on differential problem type and severity. Methods included a single assessment of variables using retrospective chart review. Subjects included 108 physicians (98 men and 10 women), who were sampled consecutively from assessments performed over a 2-year period. They represented a variety of specialties, and most were third-party referred, predominantly by state medical societies. Main outcome measures included demographic information, DSM-IV multiaxial diagnoses, the Severity of Substance-Related Disorder scale, and the type and intensity of recommended treatment. It was found that the physicians presented with a variety of conditions that were clustered into three categories: active substance use disorders (52.8%), substance use disorders in remission (17.6%), and psychiatric/behavioral problems (29.6%). An analysis of the appropriateness of matching types of treatment to these problem categories appeared to support a differential assignment process. A range in severity was also found within problem categories and was subsequently tested for correspondence with the range in intensity of recommended treatment. It was found that severity correlated strongly with recommended treatment intensity for all groups. In addition, multiple regression analyses showed that two factors, ability to sustain abstinence and emotional disturbance, were predictive of treatment intensity for the two substance use disorder subgroups (64% of variance accounted for). In the psychiatric/behavioral problem subgroup, such analysis demonstrated that the severity of difficulties with one's significant other was predictive of treatment intensity (89% of variance accounted for).


A Case of Apparent Lung Adenocarcinoma Size Reduction During Steroid Therapy.
Spontaneous regression of lung cancer is a rare phenomenon. We described a case of lung adenocarcinoma size reduction during steroid therapy. In this case, histopathologic findings showed a lung adenocarcinoma surrounded by obstructive pneumonia and inflammatory cell infiltration. Steroid use might have diminished the inflammatory response around the lung cancer, resulting in the apparent shrinkage of the lung cancer. This phenomenon is a potential pitfall in lung cancer diagnosis.


Do single people want to date a cancer survivor? A vignette study.
Qualitative studies indicated that cancer survivors may be worried about finding a partner in the future, but whether this concern is warranted is unknown. We examined single people´s interest in dating a cancer survivor, how they perceive survivors' traits, and their preferences about the timing of disclosing a cancer history. In three experimental vignette studies, dating website members (n = 324) and college students (n = 138 and n = 131) were randomly assigned to a vignette of a person with or without a history of cancer (experiment 1 & 2), or a cancer survivor beyond or during active follow-up (experiment 3). Respondents rated their interest in dating this fictive person, this person's traits, and indicated their preferences about the timing of disclosure. ANOVAs with main and interaction effects of condition, gender, and relationship history were conducted, partial eta squared and Cohen's d were used to estimate the magnitude of effects. Correlations were used to investigate relationships between interest in a date and assessment of traits. Cancer survivors' traits were assessed more positively, but interest to date them did not differ from healthy vignettes for both men and women. However, widowed respondents were much less interested in a date with a cancer survivor, and women showed less interest in a cancer survivor during active follow-up relative to survivors beyond follow-up. Most respondents wanted to hear about the cancer diagnosis after a few dates, hardly anyone wanted to hear about this before the first date (2% - 5%). Cancer survivors do not have to expect any more problems in finding a date than people without a cancer history, and can wait a few dates before disclosing. Survivors dating widowed people and survivors in active follow-up could expect more hesitant reactions and should disclose earlier.


Māori women and menopause.
Māori are the indigenous people of New Zealand who in total make up 14.5% of the population. Although this group has a significantly lower life expectancy than non-Māori, coupled with increased rates of mortality and morbidity, very little is known about the menopausal health needs of older Māori women. As the first step in addressing the health needs of this group, older Māori women's definitions, attitudes, symptoms, expectations and health needs at menopause need to be identified and described. The study Ngā Ruahine or "Māori in Menopause" is the foundation study of the Aotearoa Women's Health Initiative (AWHI). AWHI is a women's health programme being developed by the Wellington School of Medicine, which involves a suite of studies. The objective is to describe the journey of older Māori women through menopause and beyond and to compare and contrast the experience of Māori women from both traditional and contemporary upbringings, with reference to the Pākehā (European) population. It is hoped that this work could lead to further studies such as, for example, a longitudinal observational study looking at older New Zealand women. The potential significance of this approach is discussed.


Long-Term Effects of Continuous Subcutaneous Insulin Infusion on Glucose Control and Microvascular Complications in Patients With Type 1 Diabetes.
We investigated the long-term effects of continuous subcutaneous insulin infusion (CSII) on glucose control and microvascular complications in patients with type 1 diabetes (T1D). A total of 157 patients (59 M/98 W; age 39.1 ± 14.8 years) with T1D who switched from multiple daily injections to CSII and used CSII for at least one year were included. HbA1c levels and status of microvascular complications before and while under CSII were analyzed, retrospectively. The follow-up period was 4.0 ± 1.5 years. HbA1c significantly decreased from 8.4 ± 1.3 to 7.7 ± 1.3% (68 ± 14 to 61 ± 14 mmol/mol) after 1-year CSII and remained lower than pre-CSII levels during four years. Patients with pre-CSII HbA1c >8.0% (64 mmol/mol) showed significant improvement of HbA1c for four years, while those with pre-CSII HbA1c <8.0% showed no significant change. The prevalence of retinopathy, albuminuria, and chronic kidney disease (CKD) were respectively 39%, 12%, and 9% at CSII initiation. During follow-up, the incidence of retinopathy, albuminuria, and CKD were 3.6, 2.5 and 1.4/100 patient-years. Onset or progression of retinopathy occurred in 16 (27.1%) patients with diabetes duration >15 years, and in three (4.3%) patients with diabetes duration <15 years ( P < .01). CSII was effective in improving HbA1c for up to four years, specifically in patients with HbA1c >8% (64 mmol/mol) prior to CSII. Incidence and progression rates of retinopathy and albuminuria were low, particularly in patients with a diabetes duration <15 years at CSII initiation. These results argue for not delaying a proposal of CSII initiation in T1D with sustained HbA1c >8% (64 mmol/mol).


Two-distinct polymer ubiquitin conjugates by photochemical grafting-from.
Protein-polymer bioconjugates present a way to make enzymes more efficient and robust for industrial and medicinal applications. While much work has focused on mono-functional conjugates, i.e. conjugates with one type of polymer attached such as poly(ethylene glycol) or poly(N-isopropylacrylamide), there is a practical interest in gaining additional functionality by synthesizing well-defined bifunctional conjugates in a hetero-arm star copolymer architecture with protein as the core. Using ubiquitin as a model protein, a synthetic scheme was developed to attach two different polymers (OEOMA and DMAm) directly to the protein surface, using orthogonal conjugation chemistries and grafting-from by photochemical living radical polymerization techniques. The additional complexity arising from attempts to selectively modify multiple sites led to decreased polymerization performance and indicates that ICAR-ATRP and RAFT are not well-suited to bifunctional bioconjugates applications. Nonetheless, the polymerization conditions preserve the native fold of the ubiquitin and enable production of a hetero-arm star protein-polymer bioconjugate.


Time: an underestimated variable in minimizing the gender gap in medical college admission scores.
Results of medical college admission tests in Austria demonstrate the slightly worse performance of women, and are the basis for discussions around fairness and a basic science knowledge gap among female applicants. The purpose of this article was to investigate a basic science knowledge gap among female candidates of the admission test at the Medical University of Graz, and to evaluate whether the point of time of taking the examination has an influence on the test results. Observational investigations of the results of the admission test at the Medical University of Graz were performed. A total of 3405 applicants were included in the study. Statistical analyses were performed by routine methods. Male Austrian applicants are invariably more successful than female Austrian applicants when they pass the admission test immediately after completing secondary education. When female as well as male candidates pass the admission test 1 year after completion of secondary education, the differences in the results are no longer statistically significant. A basic science knowledge gap in the Austrian applicants can be confirmed. The variable time can be interpreted as an opportunity for the reduction of a basic science knowledge gap.


Medium-chain plasma acylcarnitines, ketone levels, cognition, and gray matter volumes in healthy elderly, mildly cognitively impaired, or Alzheimer's disease subjects.
Aging, amyloid deposition, and tau-related pathology are key contributors to the onset and progression of Alzheimer's disease (AD). However, AD is also associated with brain hypometabolism and deficits of mitochondrial bioenergetics. Plasma acylcarnitines (ACCs) are indirect indices of altered fatty acid beta-oxidation, and ketogenesis has been found to be decreased on aging. Furthermore, in elderly subjects, alterations in plasma levels of specific ACCs have been suggested to predict conversion to mild cognitive impairment (MCI) or AD. In this study, we assayed plasma profiles of ACCs in a cohort of healthy elderly control, MCI subjects, and AD patients. Compared with healthy controls or MCI subjects, AD patients showed significant lower plasma levels of several medium-chain ACCs. Furthermore, in AD patients, these lower concentrations were associated with lower prefrontal gray matter volumes and the presence of cognitive impairment. Interestingly, lower levels of medium-chain ACCs were also found to be associated with lower plasma levels of 2-hydroxybutyric acid. Overall, these findings suggest that altered metabolism of medium-chain ACCs and impaired ketogenesis can be metabolic features of AD.


Anthelmintic Resistance of Strongyle Nematodes to Ivermectin and Fenbendazole on Cart Horses in Gondar, Northwest Ethiopia.
A study was conducted from November 2015 to April 2016 to determine fenbendazole and ivermectin resistance status of intestinal nematodes of cart horses in Gondar, Northwest Ethiopia. Forty-five strongyle infected animals were used for this study. The animals were randomly allocated into three groups (15 horses per group). Group I was treated with fenbendazole and Group II with ivermectin and Group III was left untreated. Faecal samples were collected from each cart horse before and after treatment. Accordingly, the reduction in the mean fecal egg count at fourteen days of treatment for ivermectin and fenbendazole was 97.25% and 79.4%, respectively. It was significantly different in net egg count between treatment and control groups after treatment. From the study, resistance level was determined for fenbendazole and suspected for ivermectin. In addition, a questionnaire survey was also conducted on 90 selected cart owners to assess their perception on anthelmintics. In the survey, the most available drugs in the study area used by the owners were fenbendazole and ivermectin. Most respondents have no knowledge about drug management techniques. Hence, animal health extension services to create awareness regarding anthelmintic management that plays a key role in reducing the anthelmintic resistance parasites.


Silent Fistula of the Ascending Aorta to Pericardium by Brucella Endocarditis.
We report the case of a 26-year-old male patient with 2-week history of Brucella aortic valve endocarditis that was referred from general hospital to our hospital emergency room with pallor of the skin and mucous membranes accompanied by systemic hypotension and chest pain. Trans esophageal echocardiography (TEE) revealed a 30-mm ascending aorta at the pulmonary trunk with no evidence of the false lumen or intimal flap. TEE also showed a large vegetation of the aortic valve that limited to noncoronary sinus with moderate pericardial effusion. TEE did not showed fistula tract of nonaortic coronary sinus ring to intra mural of aorta and to pericardial cavity. The patient underwent open heart surgery with resection of destructed aortic valve and vegetation and replacement of aortic valve with prosthetic valve (Carbomedics, Sorin group. 23 mm sizes) with separated pledged suture. Debridement of aortic intra mural fistula tract and its replacement with fresh pericardial patch than performed. The pericardial cavity had moderate bloody effusion. The patient recovered uneventfully and was discharged in the 15th postoperative day. In this case, we report a rare silent clinical presentation of aortic wall fistula by vegetation and aortic ring abscess and periaortic wall hematoma, and reviewed its medical and surgical treatment.


Quantitative Characteristics of Consecutive Lengthening Episodes in Early-onset Scoliosis (EOS) Patients With Dual Growth Rods.
A prospective single-center study. The aim of this study was to record the characteristic forces and lengths observed during distraction episodes in early-onset scoliosis (EOS), and analyze their interdependencies on the key variability among the patients. The goal of the growing-rod technique is to achieve deformity correction alongside maintaining growth of the spine. The deformity correction is achieved during the initial surgery, but follow-up distraction episodes are necessary to maintain the growth. The key variables, under the control of a surgeon, that affect the growth are the applied distraction forces and the distraction lengths. Since the advent of dual growth rod technique, there have been many studies exploring the relationship between these and the actual growth. However, there is sparse evidence on the actual magnitude of distraction forces, and none on its association with patient's parameters such as sex, age, and deformity. In a consecutive series of 47 patients implanted with dual growth rods, the distraction forces (in N) and the lengths (in mm) achieved during each distraction episode and compared against the episode-specific demographics. The values obtained from each side, that is, concave and convex sides, were averaged to calculate the mean. Statistical analysis was performed using t-distribution because for each normalized time points (distraction episode). In cumulative, the distraction force increased by an amount of 268%, with 120% increase in the early stages (distractions episodes 1-6) and 68% increase in the later stages (distractions episodes 6-11), whereas the cumulative decrease in the length over 11 distractions episodes was 47%, with 34% and 20% in the early and later stages, respectively. The study does not identify any significant trend with respect to sex, age, and deformity. The distraction force and the length increased and decreased respectively with every consecutive distraction episode, with no correlation to sex, age, extent of deformity, or the extent of correction. 5.


Diphenyliodonium Ion/Et3N Promoted Csp2-H Radical Phosphorylation of Enamides.
This work reports a simple and efficient method for the direct phosphorylation of enamide under metal-free conditions. The P-centered radicals, derived from secondary phosphine oxides, are generated under mild reaction conditions in the presence of diphenyliodonium salt and Et3N and are introduced onto a range of enamides in good isolated yields. The method features broad substrate scope, good functional group tolerance, and efficient scale-up.


Characterization of muscle strength and mobility in oculopharyngeal muscular dystrophy.
Muscle weakness, and its association with mobility limitations, has received little study in oculopharyngeal muscular dystrophy (OPMD) using quantitative and standardized assessments. The objectives of this study were to (1) document upper and lower limb muscle strength, upper limb functions, fatigue, and mobility capacities; (2) compare them with reference values and across participant age groups; and (3) explore associations between muscle strength, fatigue, and mobility capacities among adults with OPMD. Thirty-four participants were included in this cross-sectional study. The following variables were assessed: quantitative maximal isometric muscle strength, grip and pinch strength, fatigue, walking speed, walking endurance, sit-to-stand, and stair ascent and descent capacities. Muscle strength was lower for older than younger participants for five muscle groups (P < .05). Walking endurance, sit-to-stand, stairs (ascent and descent), and strength of hip flexion, grip, and pinch were below 80% of reference values in participants ≥56 y old (55.3%-78.2%). Moderate to strong correlations were found between muscle strength and mobility capacities (ρ = 0.42-0.80, P < .05), and between fatigue and either muscle strength or mobility capacities (ρ = 0.42-0.75, P < .05). This study highlights the impact of OPMD on strength, endurance, and functional capacity, among others, with patients being well below reference values even before the age of 65 y. In addition to helping health professionals to offer better clinical guidance, these results will improve clinical trial readiness. The next steps will be to assess the metrological properties of outcome measures and continue to document the disease progression rate.


Arbuscular Mycorrhizal Fungal 14-3-3 Proteins Are Involved in Arbuscule Formation and Responses to Abiotic Stresses During AM Symbiosis.
Arbuscular mycorrhizal (AM) fungi are soil-borne fungi belonging to the ancient phylum Glomeromycota and are important symbionts of the arbuscular mycorrhiza, enhancing plant nutrient acquisition and resistance to various abiotic stresses. In contrast to their significant physiological implications, the molecular basis involved is poorly understood, largely due to their obligate biotrophism and complicated genetics. Here, we identify and characterize three genes termed Fm201, Ri14-3-3 and RiBMH2 that encode 14-3-3-like proteins in the AM fungi Funneliformis mosseae and Rhizophagus irregularis, respectively. The transcriptional levels of Fm201, Ri14-3-3 and RiBMH2 are strongly induced in the pre-symbiotic and symbiotic phases, including germinating spores, intraradical hyphae- and arbuscules-enriched roots. To functionally characterize the Fm201, Ri14-3-3 and RiBMH2 genes, we took advantage of a yeast heterologous system owing to the lack of AM fungal transformation systems. Our data suggest that all three genes can restore the lethal Saccharomyces cerevisiae bmh1 bmh2 double mutant on galactose-containing media. Importantly, yeast one-hybrid analysis suggests that the transcription factor RiMsn2 is able to recognize the STRE (CCCCT/AGGGG) element present in the promoter region of Fm201 gene. More importantly, Host-Induced Gene Silencing of both Ri14-3-3 and RiBMH2 in Rhizophagus irregularis impairs the arbuscule formation in AM symbiosis and inhibits the expression of symbiotic PT4 and MST2 genes from plant and fungal partners, respectively. We further subjected the AM fungus-Medicago truncatula association system to drought or salinity stress. Accordingly, the expression profiles in both mycorrhizal roots and extraradical hyphae reveal that these three 14-3-3-like genes are involved in response to drought or salinity stress. Collectively, our results provide new insights into molecular functions of the AM fungal 14-3-3 proteins in abiotic stress responses and arbuscule formation during AM symbiosis.


Anatomical Retinal Changes after Photodynamic Therapy in Chronic Central Serous Chorioretinopathy.
To evaluate anatomical retinal changes measured by spectral-domain optical coherence tomography (SD-OCT), after applying photodynamic therapy (PDT) for treatment of chronic central serous chorioretinopathy (CSC). A retrospective analysis was conducted on 43 patients (48 eyes) with chronic CSC treated with PDT. Visual acuity (VA), central retinal thickness (CRT), outer nuclear layer (ONL) thickness, subretinal fluid (SRF), and photoreceptor ellipsoid zone (EZ) measured by SD-OCT were collected at baseline and at 3, 6, and 12 months after PDT. Differences between normally distributed variables were calculated by a paired-sample t-test; p < 0.05 was considered statistically significant. Mean age was 50 ± 9.8 years. Mean time from diagnosis to PDT was 12.5 months. Baseline VA was 0.51 ± 0.24 and significantly improved (p < 0.001) to 0.74 ± 0.26 one year after PDT. CRT and SRF significantly decreased (p < 0.001) at 3, 6, and 12 months after treatment. ONL thickness and EZ did not significantly change at any point during follow-up. Not significant changes were found in the ONL or EZ 12 months after PDT.


GBDTL2E: Predicting lncRNA-EF Associations Using Diffusion and HeteSim Features Based on a Heterogeneous Network.
Interactions between genetic factors and environmental factors (EFs) play an important role in many diseases. Many diseases result from the interaction between genetics and EFs. The long non-coding RNA (lncRNA) is an important non-coding RNA that regulates life processes. The ability to predict the associations between lncRNAs and EFs is of important practical significance. However, the recent methods for predicting lncRNA-EF associations rarely use the topological information of heterogenous biological networks or simply treat all objects as the same type without considering the different and subtle semantic meanings of various paths in the heterogeneous network. In order to address this issue, a method based on the Gradient Boosting Decision Tree (GBDT) to predict the association between lncRNAs and EFs (GBDTL2E) is proposed in this paper. The innovation of the GBDTL2E integrates the structural information and heterogenous networks, combines the Hetesim features and the diffusion features based on multi-feature fusion, and uses the machine learning algorithm GBDT to predict the association between lncRNAs and EFs based on heterogeneous networks. The experimental results demonstrate that the proposed algorithm achieves a high performance.


Alteration of serpin specificity by a protein cofactor. Vitronectin endows plasminogen activator inhibitor 1 with thrombin inhibitory properties.
Serine protease inhibitors ("serpins") are highly homologous proteins which inhibit selected "target" serine proteases by acting as a pseudo-substrate. Their specificity is primarily determined by the amino acid sequence around the carboxyl-terminally located reactive center (P1-P1'). In addition, the association rate constant between a serpin and a serine protease can be dramatically increased by non-protein cofactors, such as heparin in the case of thrombin inhibition by antithrombin III. In an attempt to alter the specificity of PAI-1 from an inhibitor of the fibrinolytic system to an inhibitor of coagulation, we replaced P1-P1' or P3 through P3' of the reactive center of PAI-1 by the corresponding residues of antithrombin III and assessed whether the mutant proteins, purified from lysates of transformed Escherichia coli cells, had acquired thrombin inhibitory properties. The experiments were performed in the presence and absence of vitronectin, a multifunctional protein which has been shown to bind PAI-1 in plasma and in the matrix of endothelial cells. The second-order rate constants for t-PA inhibition of "wild-type" PAI-1 and PAI P1-P1'ATIII, irrespective of the presence of vitronectin, were similar, whereas replacing P3-P3' resulted in a 40-fold decrease of the second-order rate constant towards t-PA, again independent of vitronectin. In the absence of vitronectin, reactivity of PAI-1 and its "antithrombin III-like" variants towards thrombin was slow; however, PAI-1 P3-P3' ATIII had a 10-fold higher k1 than wild-type PAI-1 (1.3 x 10(4) M-1 s-1 versus 1.1 x 10(3) M-1 s-1). In contrast, in the presence of vitronectin, PAI-1 and even more rapidly PAI-1 P3-P3'ATIII were found to be effective thrombin inhibitors, with k1 values of 2.2 x 10(5) M-1s-1 and 1.8 x 10(6) M-1 s-1, respectively. Thus, in the presence of vitronectin, PAI-1 P3-P3'ATIII displays a 3-fold higher k1 with thrombin than with t-PA. It is shown that vitronectin enhances, in a dose-dependent manner, the formation of sodium dodecyl sulfate-resistant complexes between PAI-1 or mutants thereof and thrombin. Therefore, vitronectin is the first protein described to function as a cofactor for serpin specificity. PAI-1 is proposed to be a versatile inhibitor which, in the presence of vitronectin, can modulate both coagulation and fibrinolysis.


A Direct Alcohol Fuel Cell Driven by an Outer Sphere Positive Electrode.
Molecular oxygen, the conventional electron acceptor in fuel cells poses challenges specific to direct alcohol fuel cells (DAFCs). Due to the coupling of alcohol dehydrogenation with the scission of oxygen on the positive electrode during the alcohol crossover, the benchmark Pt-based air cathode experiences severe competition and depolarization losses. The necessity of heavy precious metal loading with domains for alcohol tolerance in the state of the art DAFC cathode is a direct consequence of this. Although efforts are dedicated to selectively cleave oxygen, the root of the problem being the inner sphere nature of either half-cell chemistry is often overlooked. Using an outer sphere electron acceptor that does not form a bond with the cathode during redox energy transformation, we effectively decoupled the interfacial chemistry from parasitic chemistry leading to a DAFC driven by alcohol passive carbon nanoparticles, with performance metrics ∼8 times higher than Pt-based DAFC-O2.


[Reaction of the salivary glands to acute stress].
Experiment on male rats has shown that acute stress suppressed amylase and superoxide dismutase activity in the submandibular salivary glands. The influence of short repeated stresses weakened the inhibiting effect of the acute stress on the activity of enzymes. A conclusion is drawn about the high sensibility of salivary glands to stress influences.


Recent setbacks in measles elimination: the importance of investing in innovations for immunizations.
The recent setbacks in efforts to achieve measles elimination goals are alarming. To reverse the current trends, it is imperative that the global health community urgently intensify efforts and make resource commitments to implement evidence-based elimination strategies fully, including supporting research and innovations. The Immunization Agenda 2030: A Global Strategy to Leave No One Behind (IA2030) is the new global guidance document that builds on lessons learned and progress made toward the GVAP goals, includes research and innovation as a core strategic priority, and identifies measles as a "tracer" for improving immunisation services and strengthening primary health care systems. To achieve vaccination coverage and equity targets that leave no one behind, and accelerate progress toward disease eradication and elimination goals, sustained and predictable investments are needed for the identified research and innovations priorities for the new decade.


Association of Interleukin-10 Polymorphisms (rs1800872, rs1800871, and rs1800896) with Predisposition to IgA Nephropathy in a Chinese Han Population: A Case-Control Study.
IgA nephropathy (IgAN) is a common form of primary glomerulonephritis worldwide. Previous studies indicated that IL-10 single nucleotide polymorphisms (SNP) play an important role in IgAN pathogenesis, but the results were controversy. This study aimed to investigate the association between IL-10 SNPs (rs1800872, rs1800871, and rs1800896) with IgAN in a Chinese Han population. We conducted a case-control study that included 351 patients with IgAN and 310 age-, gender- and ethnicity-matched healthy controls. Three promoter SNPs (rs1800872, rs1800871, and rs1800896) of IL-10 were genotyped by Sequenom MassARRAY. Odds ratios (ORs) with 95% confidence intervals (CI) were used to assess the relationship with IgAN. We found that the rs1800896 did not correlate with IgAN risk, whereas rs1800872 and rs1800871 were significantly associated with increased IgAN risk in all genetic models. The haplotype analysis indicated that the CCA haplotype was associated with increased IgAN risk (OR = 1.36; 95% CI = 1.05-1.75). Moreover, there were no associations between these SNPs and blood pressure or gender, whereas the rs1800896 variant was correlated with higher 24-hour urine protein in patients with IgAN. Taken together, these results suggest that IL-10 is a susceptibility gene in patients with IgAN.


Rational antibiotics therapy in bacterial meningitis.
Acute bacterial meningitis is one of the most important causes of morbidity and mortality in developing countries. Though a wide range of antibiotics is available for therapy, judicious and rational use of antimicrobial agents needs to be ascertained. The choice of antimicrobial agents depends mainly on the age of the patient and its CSF penetrability. Neonatal meningitis is commonly caused by Gram Negative organisms such E. coli, Klebsiella and Pseudomans;Group B streptococciand Listeria, though other organisms like Staphylococcus sp. also contribute. The neonatal meningitis is best treated with a combination of amplicillin and a third generation cephalosporin given for 14-21 days. Post-neonatal meningitis usually occurs due to S. pneumoniae, N. meningitidis and H. influenzae and is best treated with third generation cephalosporins used with or without crystalline penicillin or ampicillin depending on the clinical situation. The therapy should be modified, if necessary, on availability of culture sensitivity report. The use of dexamethasone in meningitis due to the organisms other than H. influenzae still remains controversial.


Is acriflavine an efficient co-drug in chemotherapy?
Cancer is a global health problem being the second worldwide cause of deaths right after cardiovascular diseases. The main methods of cancer treatment involve surgery, radiation and chemotherapy with an emphasis on the latter. Thus development of nanochemistry and nanomedicine in a search for more effective and safer cancer treatment is an important area of current research. Below, we present interaction of doxorubicin and acriflavine and the cytotoxicity of these drug nano-complexes towards cervical cancer (HeLa) cells. Experimental results obtained from NMR measurements and fluorescence spectroscopy show that the drugs' interaction was due to van der Waals forces, formation of hydrogen bonds and π-π stacking. Quantum molecular simulations confirmed the experimental results with regard to existing π-π stacking. Additionally it was shown that, at the level of theory applied (DFT, triple zeta basis set), the stacking interactions comprise the most preferable interactions (the lowest ΔG ca. -12 kcal mol-1) both between the molecules forming the acriflavine system and between the other component - another drug (doxorubicin) dimer. Biological tests performed on HeLa cells showed high cytotoxicity of the complexes, comparable to free drugs (ACF and DOX), both after 24 and 48 hours of incubation. For non-cancerous cells, a statistically significant difference in the cytotoxicity of drugs and complexes was observed in the case of a short incubation period. The results of the uptake study showed significantly more efficient cellular uptake of acriflavine than doxorubicin, whether administered alone or in combination with an anthracycline. The mechanism determining the selective uptake of acriflavine and ACF : DOX complexes towards non-cancer and cancer cells should be better understood in the future, as it may be of key importance in the design of complexes with toxic anti-cancer drugs.


Greek economic crisis and health care reforms: correcting the wrong prescription.
In an era of economic crisis in Greece and with many uninsured citizens, the Troika (lenders of Greece) suggests reforms and promotes the internal market, resulting in a public-private system becoming more privatized. This article contradicts these proposals and attempts to suggest the necessary reforms to achieve equity of access for all and to promote efficiency, taking into account the existing needs of the population and the recession of the Greek economy.


Study on the gene and phenotypic characterisation of autosomal recessive demyelinating motor and sensory neuropathy (Charcot-Marie-Tooth disease) with a gene locus on chromosome 5q23-q33.
To report the occurrence of the autosomal recessive form of demyelinating Charcot-Marie-Tooth disease (CMT) with a locus on chromosome 5q23-33 in six non-related European families, to refine gene mapping, and to define the disease phenotype. In an Algerian patient with autosomal recessive demyelinating CMT mapped to chromosome 5q23-q33 the same unique nerve pathology was established as previously described in families with a special form of autosomal recessive demyelinating CMT. Subsequently, the DNA of patients with this phenotype was tested from five Dutch families and one Turkish family for the 5q23-q33 locus. These patients and the Algerian families showed a similar and highly typical combination of clinical and morphological features, suggesting a common genetic defect. A complete cosegregation for markers D5S413, D5S434, D5S636, and D5S410 was found in the families. Haplotype construction located the gene to a 7 cM region between D5S643 and D5S670. In the present Dutch families linkage disequilibrium could be shown for various risk alleles and haplotypes indicating that most of these families may have inherited the underlying genetic defect form a common distant ancestor. This study refines the gene localisation of autosomal recessive demyelinating CMT, mapping to chromosome 5q23-33 and defines the phenotype characterised by a precocious and rapidly progressive scoliosis in combination with a relatively mild neuropathy and a unique pathology. Morphological alterations in Schwann cells of the myelinated and unmyelinated type suggest the involvement of a protein present in both Schwann cell types or an extracellular matrix protein rather than a myelin protein. The combination of pathological features possibly discerns autosomal recessive demyelinating CMT with a gene locus on chromosome 5q23-33 from other demyelinating forms of CMT disease.


Bichromatic UV detection system for atomically-resolved imaging of ions.
We present a compact bichromatic imaging system, located outside of the vacuum chamber of a trapped ion apparatus that collects the fluorescence of 230.6 and 369.5 nm photons simultaneously on a shared electron-multiplying charge-coupled device (EMCCD) camera. The system contains two lens doublets, consisting of a sphere and an asphere. They provide a numerical aperture of 0.45 and 0.40 at 230.6 and 369.5 nm, respectively, and enable spatially resolved state detection with a large field of view of 300 μm for long 115In+/172Yb+ Coulomb crystals. Instead of diffraction-limited imaging for one wavelength, the focus in this system is on simultaneous single-ion resolved imaging of both species over a large field, with special attention to the deep UV wavelength (230.6 nm) and the low scattering rate of In+ ions. The introduced concept is applicable to other dual-species applications.


Chronic B cell malignancies and bone marrow microenvironment.
Chronic B-lymphoid malignancies depend upon supportive interactions within specific microenvironments. Follicular lymphoma (FL), chronic lymphocytic leukaemia (CLL) and multiple myeloma (MM) cells accumulate in the bone marrow (BM) where they receive survival or growth signals from by-stander cells. However, they deeply differ in their interaction with the microenvironment. We propose a model where FL and CLL recreate in the BM the microenvironment most suitable to their growth by 'importing' the normal cells that usually nurse them in secondary lymphoid organs. In contrast, MM takes advantage of the actual BM microenvironment by 'instructing' it through an abnormal activation state.


Functional expression of the human UDP-galactose transporters in the yeast Saccharomyces cerevisiae.
We describe the functional expression of the putative human Golgi UDP-galactose transporters (hUGT1 and hUGT2) in the yeast Saccharomyces cerevisiae. Both hUGT1 and hUGT2 were expressed under the control of the yeast constitutive GAPDH promoter. The expression level of hUGT1 seemed to be considerably lower than that of hUGT2, although hUGT1 has an amino acid sequence identical to that of hUGT2 except for 5 amino acid residues at the C-terminus. The hUGT product was expressed in the membranes of Golgi and other organellar compartments. The membrane vesicles prepared from the hUGT1- or the hUGT2-expressing yeast cells exhibited UDP-galactose specific transport activity. The apparent Km values of the yeast-expressed hUGT1 and hUGT2 for UDP-galactose were 1.2 and 2 microM, respectively, which were comparable with the Km obtained with mammalian Golgi vesicles. Transport was dependent on temperature and integrity of vesicles, and was inhibited by UMP, as observed with mammalian Golgi vesicles. Our results demonstrate that the previously described hUGT1 and hUGT2 encode the UDP-galactose transporters, rather than regulatory proteins. The development of a convenient yeast expression system should facilitate analysis of the structure-function relationships of the UDP-galactose transporters.


Quantification of sensitivity of endothelial cell markers for the astrocytoma and oligodendroglioma tumours.
Angiogenesis, the formation of new blood vessels, is necessary for tumour growth. The aim of this study was to quantify the sensitivity of five endothelial cell markers CD31/CD34-mix, CD31, CD34, lectin UEA-1 and FVIII-rag. Paraffin-embedded tumour tissue from 15 patients with astrocytomas grades II-IV and oligodendrogliomas grades II-III was used Sections of 2 microm were stained. Seven serial sections from each of the 15 tumours enabled consecutive examination of the vessels with all five markers and with two interposed hematoxylin-eosin (H&E) sections as controls. Among the endothelial cell markers, the mix CD31/CD34 showed the highest sensitivity with 79% and 99%, respectively, when applied in astrocytomas grade II and grades III-IV and 86% when applied in oligodendrogliomas. The study has shown that the sensitivity of the five endothelial cell markers varied. The mix CD31/CD34 was superior and seems to be a useful marker for quantification of angiogenesis.


Roles of gonad-inhibiting hormone in the protandric simultaneous hermaphrodite peppermint shrimp†.
To date, the molecular mechanisms of the unique gonadal development mode known as protandric simultaneous hermaphroditism (PSH) are unclear in crustaceans. In this study, cDNA of a gonad-inhibiting hormone (Lv-GIH1) was isolated from the PSH peppermint shrimp Lysmata vittata, and its expression was exclusively found in the eyestalk ganglion. Real-time quantitative polymerase chain reaction (qRT-PCR) revealed that the expression of Lv-GIH1 increased during gonadal development of the functional male stages but decreased significantly at subsequent simultaneous hermaphroditism stage. Further in vitro experiment showed that recombinant GIH1 protein (rGIH1) effectively inhibited Vg expression in the cultured hepatopancreas tissues while the short-term injection of GIH1-dsRNA resulted in reduced expression of Lv-GIH1 and upregulated expression of Vg in the hepatopancreas. Moreover, long-term rGIH1 injection led to significantly reduced expression of Lv-Vg, Lv-VgR, and Lv-CFSH1, subdued growth of oocytes, and feathery setae as a secondary sexual characteristic in females. Interestingly, while germ cells in testicular part were suppressed by rGIH1 injection, the expression of Lv-IAGs showed no significant difference; and long-term GIH1-dsRNA injection results were contrary to those of rGIH1 injection. Taken together, the results of this study indicate that Lv-GIH1 is involved in gonadal development and might also participate in controlling secondary sexual characteristic development in L. vittata by inhibiting Lv-CFSH1 expression.


A registry analysis of damage to the deceased donor pancreas during procurement.
Surgical injury to the pancreas is thought to occur commonly during procurement. The UK Transplant Registry was analyzed to determine the frequency of pancreatic injuries, identify factors associated with damage, and assess the impact of injuries on graft survival. Twelve hundred ninety-six pancreata were procured from donation after brain death donors, with 314 (19.5%) from donation after circulatory death donors. More than 50% of recovered pancreata had at least one injury, most commonly a short portal vein (21.5%). Liver donation, procurement team origin, hepatic artery (HA) arising from the superior mesenteric artery (SMA), and increasing donor BMI were associated with increased rates of pancreas damage on univariate analyses; on multivariate analysis only the presence of an HA from the SMA remained significant (p = 0.02). Six hundred forty solid organ pancreas transplants were performed; 238 had some form of damage. Overall, there was no difference in graft survival between damaged and undamaged organs (p = 0.28); however, graft loss was significantly more frequent in pancreata with arterial damage (p = 0.04) and in those with parenchymal damage (p = 0.05). Damage to the pancreas during organ recovery is more common than other organs, and meticulous surgical technique and awareness of damage risk factors are essential to reduce rates of procurement-related injuries.


Regulation of human jejunal glycolytic enzymes by oral folic acid.
The effect of oral folic acid on jejunal glycolytic enzyme activity in five fasting obese patients and in three normal male volunteers on a constant 3000 cal diet was studied. The glycolytic enzymes, fructokinase, hexokinase, glucokinase, fructose-1-phosphate aldolase, and fructose diphosphate aldolase, and the disaccharidases, sucrase, maltase, and lactase were measured. In both the fasting patients and the normal volunteers, oral folic acid significantly increased the jejunal glycolytic enzyme activities but had no effect on disaccharidase activity. When oral folic acid was discontinued in the normal volunteers, the glycolytic enzyme activities returned to control values. In the obese patients, refeeding and folic acid caused a further increase in glycolytic enzyme activities above that seen with fasting and folic acid. In contrast to oral folic acid, intramuscular folic acid, oral vitamin B(12), and oral tetracycline had no effect on glycolytic enzyme activities. These studies demonstrate that oral folic acid which is neither a substrate nor a coenzyme of these enzymes, increases human jejunal glycolytic enzyme activity in a specific fashion. This would appear to be an action of oral folic acid which has not been recognized previously.


The impact of a 12-week resistance training program on strength, body composition, and self-concept of Hispanic adolescents.
Current evidence suggests that a resistance training program may be physically and psychologically beneficial for adolescents. The purpose of this study was to examine the effects of a structured resistance training program on strength, body composition, and self-concept in normal and overweight Hispanic adolescents. Male and female participants (n = 28; 16.1 +/- 0.2 y; 164.5 +/- 1.4 cm; 63.3 +/- 2.5 kg; 20.0 +/- 1.7% body fat [BF]) were recruited from a predominantly Hispanic high school. Prior to the 12-week program, strength, body composition, and self-concept were assessed. Subjects were randomly assigned to a control group (CON; n = 15) or to a resistance training group (RT; n = 13) that participated in supervised strength training 3 days/week. All measures were repeated at the end of the 12-week program. RT had significantly greater strength increases for bench press (p < 0.001), seated row (p = 0.002), shoulder press (p < 0.001), and squats (p = 0.002). RT had significant reductions in %BF (p = 0.001), whereas CON had slightly increased %BF. RT had an increase in condition/stamina competence (p = 0.008), attractive body adequacy (p = 0.017), and global self-worth (p = 0.013) from pretest to posttest, whereas no change was observed for CON. In conclusion, resistance training resulted in significant physiological and psychological improvements in Hispanic adolescents compared to typical school-based activities. These findings indicate that resistance training can be incorporated into the activities of Hispanic adolescents to promote improved health and fitness.


Planning for a pediatric disaster -- experience gained from caring for 1600 Vietnamese orphans.
The sudden arrival of 1600 Vietnamese orphans in San Francisco required the rapid development of a co-ordinated disaster plan, including the overnight establishment of a 1000-bed pediatric field hospital. The plan required rapid identification and involvement of lay and governmental resources, acute medical triage and provision of ongoing medical care and basic nurturing services and eventual discharge to adoptive families. Because one third of the orphans were under six months of age, conventional nursery resources were insufficient, and a "warehouse" model was implemented. This process required development of a specialized transportation and communication system, the services of 800 physicians, 1400 nurses, and 3200 volunteers and 162 back-up acute hospital beds. Disaster planning in most sizable American cities has focused on the problems of adults. Because of the unusual problem presented by infants and small children, we recommend that cities carefully evaluate their disaster planning with special reference to the needs of children.