Investigation of a Multistate Outbreak of Listeria monocytogenes Infections Linked to Frozen Vegetables Produced at Individually Quick-Frozen Vegetable Manufacturing Facilities.
In 2016, the U.S. Food and Drug Administration (FDA), the Centers for Disease Control and Prevention (CDC), and state partners investigated nine Listeria monocytogenes infections linked to frozen vegetables. The investigation began with two environmental L. monocytogenes isolates recovered from Manufacturer A, primarily a processor of frozen onions, that were a match by whole genome sequencing (WGS) to eight clinical isolates and historical onion isolates with limited collection details. Epidemiologic information, product distribution, and laboratory evidence linked suspect food items, including products sourced from Manufacturer B, also a manufacturer of frozen vegetable/fruit products, with an additional illness. The environmental isolates were obtained during investigations at Manufacturers A and B. State and federal partners interviewed ill people, analyzed shopper card data, and collected household and retail samples. Nine ill persons between 2013 and 2016 were reported in four states. Of four ill people with information available, frozen vegetable consumption was reported by three, with shopper cards confirming purchases of Manufacturer B brands. Two identified outbreak strains of L. monocytogenes (Outbreak Strain 1 and Outbreak Strain 2) were a match to environmental isolates from Manufacturer A and/or isolates from frozen vegetables recovered from open and unopened product samples sourced from Manufacturer B; the investigation resulted in extensive voluntary recalls. The close genetic relationship between isolates helped investigators determine the source of the outbreak and take steps to protect public health. This is the first known multistate outbreak of listeriosis in the United States linked to frozen vegetables and highlights the significance of sampling and WGS analyses when there is limited epidemiologic information. Additionally, this investigation emphasizes the need for further research regarding food safety risks associated with frozen foods.


An activity phosphorylating tyrosine in polyoma T antigen immunoprecipitates.
Polyoma T antigen immunoprecipitates contain a protein kinase-like activity which preferentially phosphorylates material of 50-60,000 daltons molecular weight. Phosphorylation is not diminished in extracts of polyoma tsA mutant-infected cells shifted to the nonpermissive temperature late in infection, conditions which inactivate the large T antigen. Phosphorylation is reduced or absent in cells infected with polyoma host range nontransforming (hr-t) mutants, which have defective small and medium T antigens. The major acceptor of phosphate is not the heavy chain of immunoglobulin, but appears to be the polyoma medium T antigen. The large T antigen is also phosphorylated, but usually to a lower specific activity. In terms of acid and alkali sensitivity and electrophoretic and chromatographic mobility in one and two dimensions, the phosphorylated residue behaves identically to phosphotyrosine and differently than phosphorylated serine, threonine, lysine and histidine.


Proximal thoracic aorta dimensions after continuous-flow left ventricular assist device implantation: Longitudinal changes and relation to aortic valve insufficiency.
In this study we examined the impact of continuous-flow left ventricular assist device (CF-LVAD) support on proximal thoracic aorta dimensions. Aortic root and ascending aorta diameter were measured from serial echocardiograms before and after CF-LVAD implantation in patients with ≥6 months of support, and correlated with the development of >mild aortic valve insufficiency (AI). Of 162 patients included, mean age was 58 ± 11 years and 128 (79%) were male. Seventy-nine (63%) were destination therapy patients. Mean aortic root and ascending aorta diameters at baseline, 1 month, 6 months, 12 months and long-term follow-up (mean 2.0 ± 1.4 years) were 3.5 ± 0.4, 3.5 ± 0.3, 3.9 ± 0.3, 3.9 ± 0.2 and 4.0 ± 0.3, and 3.3 ± 0.2, 3.3 ± 0.3, 3.6 ± 0.2, 3.6 ± 0.3 and 3.6 ± 0.3 cm, respectively. Only change in aortic root diameter from 1-month to 6-month follow-up reached statistical significance (p = 0.03). Nine (6%) patients had accelerated proximal thoracic aorta expansion (>0.5 cm/year), occurring predominantly in the first 6 months after implantation. These patients were older and more likely to have hypertension and baseline proximal thoracic aorta dilation. Forty-five (28%) patients developed >mild AI at long-term follow-up, including 7 of 9 (78%) of those with accelerated proximal thoracic aorta expansion. All 7 had aortic valves that remained closed throughout the cardiac cycle, and this, along with duration of CF-LVAD support and increase in aortic root diameter, were significantly associated with developing >mild AI. CF-LVAD patients have small increases in proximal thoracic aorta dimensions that predominantly occur within the first 6 months after implantation and then stabilize. Increasing aortic root diameter was associated with AI development.


Distinctive alterations of invasiveness, drug resistance and cell-cell organization in 3D-cultures of MCF-7, a human breast cancer cell line, and its multidrug resistant variant.
Growth of human tumor cells as three-dimensional (3D) multicellular spheroids modifies their invasive properties. Here we study the differences in the biological features of MCF-7, a human breast cancer cell line, and its multidrug resistant variant (MDR-MCF-7) cultured as spheroids or as monolayers. Three-dimensional culture decreased the proliferative rate of both cell lines, reduced the drug sensitivity of MCF-7 cells and did not affect the resistance of MDR-MCF-7 cells. Transmission electron microscopic studies and intercellular junctions labeling showed that MCF-7 spheroids had a junctional system involving E-cadherin, tight-junctions and desmosomes. In MDR-MCF-7 cell spheroids, cell cohesion was mostly due to membrane interdigitations. MDR-MCF-7 cells, but not their parental counterpart, displayed a higher invasive potential when cultured as spheroids, as shown in the Boyden chamber assay. 3D-induced invasiveness was correlated with serine protease and plasminogen activator (PA) secretion. MCF-7 cells did not show any tendency to invade, whatever the mode of culture. These results show that 3D-cultures as spheroids distinctively altered structural features of parental and MDR-MCF-7 cells. In MCF-7 cells, 3D-culture increased cell-cell contacts and drug resistance; in MDR-MCF-7 cells, it induced invasive properties.


Developing the Serious Games potential in nursing education.
Shortened hospital stays, high patient acuity and technological advances demand that nurses increasingly make decisions under conditions of uncertainty and risk (Ebright et al., 2003). With rising trends towards out-patient care, nurses will need to perform complex problem-solving within a dynamic and changing environment for which there is not one clear solution (Schofield et al., 2010; Wolff et al., 2009). The development of sharp clinical reasoning skills, as well as skills in detection, monitoring, investigation and evaluation are therefore essential (Aitken et al., 2002). Yet few nursing students have long-term exposure to home-care and community situations. This is primarily due to scarce human resources and the time-consuming requirements of student supervision (Duque et al., 2008). When students are given the opportunity to experience home-care or community visits these tend to be unstructured leading to wide variations in their competencies. New pedagogical tools are needed to adequately and consistently prepare nurses for the skills they will need to care for patients outside acute care settings. Advances in Information and Communications Technologies (ICT) offer an opportunity to explore innovative pedagogical solutions that could help students develop these skills in a safe environment. A three-phased project is underway that aims to create and test a Serious Game to improve nurses' clinical reasoning and detection skills in home-care and community settings. The first phase of this project involves the development of a scenario, the game engine and the graphic design and will be the focus of this paper. The second and third phases will test the Serious Game as an educational intervention and will be reported in subsequent papers.


Do patients undergoing physical therapy in a rehabilitation center have a high prevalence of pelvic floor dysfunction and psychological disorders? A cross-sectional study.
Prevalence of pelvic floor dysfunction (PFD) and its relationship with anxiety in a population undergoing physical therapy treatment in Rehabilitation Centers seems to have been little investigated in the literature. 1) to investigate the prevalence of PFD, anxiety, depression; 2) to assess quality of life (QoL) in patients undergoing physical therapy in a Rehabilitation Center, 3) to compare the results by sex; and 4) to assess the relationship between PFD and anxiety, depression, and QoL. This cross-sectional study included participants receiving physical therapy care in a Rehabilitation Center. Validated questionnaires were used to assess PFD, QoL, depression, and anxiety. The Chi-square test, Pearson's correlation coefficient, and a binary logistic regression model were used for data analysis. 253 participants (56.9% female) were included, 45% of them reported at least one PFD symptom. Females had higher prevalence of urinary incontinence (UI) (28% vs 14%); constipation (25% vs 10%); sexual dysfunction (75% vs 9%); anxiety (47% vs 35%); and depression (34% vs 17%) than males. A weak correlation was found between anxiety and depression with UI and sexual dysfunction for females. For all participants, poor QoL was found in physical functioning, physical role, bodily pain and emotional role. Being elderly (OR: 2.58 [1.24, 5.37]), partnered (OR: 1.82 [1.04, 3.17]), female (OR: 3.38 [1.91, 5.99]), and anxious (OR: 2.03 [1.14, 3.62]) were risk factors for reporting PFD. This study found a high prevalence of PFD symptoms in patients attending a Rehabilitation Center. All symptoms except fecal incontinence were more prevalent in females than in males. There was a weak correlation between UI with QoL and psychological disorders among females.


Lipoprotein and apolipoprotein distribution in Zucker rats following an endurance running program.
We examined the response to 12 weeks of endurance running of the obese Zucker rat and its lean littermate with regard to changes in serum lipids, lipoproteins and apoproteins. The obese Zucker rat is hyperlipoproteinemic, characterized by elevated serum triglyceride and cholesterol levels primarily associated with the very low density lipoprotein (VLDL) fraction. In lean Zucker rats, training did not affect the concentrations of serum lipids or apolipoproteins. In marked contrast, obese Zucker rats that were trained had significant decreases in serum concentrations of triglycerides, free and esterified cholesterol, and apolipoprotein B compared to their sedentary counterparts. Training obese rats caused an increase in the serum concentration of apolipoprotein E (HDL fraction). In contrast, training did not affect the concentration of Apo E in lean rats. The VLDL fraction was most affected by training obese rats showing marked 50-65% decreases in VLDL triglyceride and VLDL cholesterol. HDL cholesterol was unchanged in lean rats whereas training prompted a 29% increase in obese rats. These data show that exercise training altered the metabolic abnormalities of obese Zucker rats which are responsible for the accumulation in serum of VLDL, lipids and apolipoproteins.


Cyperus Rotundus L. extract suppresses RANKL-induced osteoclastogenesis through NFATc1/c-fos downregulation and prevent bone loss in OVX-induced osteoporosis rat.
Cyperus Rotundus L. (CyR) has been widely used for the treatment of gynecologic disorder. Recent studies have reported that CyR can prevent the formation of cystic follicles and ovarian malfunction. However, the effects of CyR on osteoclastogenesis and postmenopausal osteoporosis remain unknown. This study was aimed to investigate the preventive effects of CyR on RANKL-induced osteoclast formation and ovariectomy (OVX)-induced bone loss. In this in vitro study, we investigate the anti-osteoporotic effect of CyR on receptor activator of nuclear factor kappa-B ligand (RANKL)-induced osteoclastogenesis, the formation of tartrate-resistant acid phosphatase (TRAP) multinucleated cells, pit formation, transcription factors such as NFATc1 and c-Fos, and mRNA expression of osteoclast-associated genes were investigated. Forty 12-weeks female Sprague-Dawley rats for in vivo effect of CyR were used and OVX rat model was determined. The rats were randomly assigned into sham group and four OVX groups, i.e. OVX with D.W; OVX with estradiol (E2, 100μg/kg/day), OVX with CyR-L (16mg/kg/day), OVX with CyR-H (160mg/kg/day). The treatment lasted for 8weeks. CyR inhibited osteoclast differentiation and pit formation in the RANKL-induced osteoclastogenesis of RAW 264.7 cells. Reverse transcription polymerase chain reaction analysis also showed that CyR reduced the mRNA expression of osteoclast-associated genes such as carbonic anhydrase II, TRAP, RANK, cathepsin K, matrix metalloproteinase 9, nuclear factor of activated T cells cytoplasmic 1 (NFATc1), and c-Fos. In addition, CyR decreased protein levels of NFATc1 and c-Fos. CyR inhibited trabecular bone loss in the femur caused by OVX. The results of this study indicate that CyR inhibits the RANKL-induced osteoclast differentiation in RAW 264.7 cells and trabecular bone loss in OVX rats.


Fate of PCDD/PCDF during mechanical-biological sludge treatment.
In this preliminary study the seventeen 2,3,7,8-substituted congeners of PCDD/PCDF were analyzed at the inlet and outlet water and for three sewage sludge samples taken from different treatment stages to check behaviours of PCDD/PCDF at a municipal wastewater treatment plant (MWTP) in Poland. At the inlet (untreated sewage) water dominated PCDD congeners, whereas in the outlet (treated water) dominated the PCDF congeners. The octaCDD, 1,2,3,4,6,7,8-heptaCDD/CDF and octaCDF congeners dominated in all of the sludge samples. The total toxicity load gradually increased in the series excess, digested and dewatered sludge and amounted to 12.2, 14.4 and 16.9ngI-TEQkg(-1).


Plasma treatments of PET meshes for fuel-water separation applications.
Sulphur hexafluoride (SF(6)) plasma treatments and hexamethyl disiloxane (HMDSO) plasma polymerisation were performed on poly(ethylene terephthalate) (PET) meshes and the resulting wettability against liquids having very different surface tensions were investigated at the light of a possible use of the materials in the fuel/water separation technology. Surface modification of the meshes owing to HMDSO plasma polymerisation followed by SF(6) plasma treatment was also investigated. Hydrophobic performances were characterised refining the conventional Wilhelmy dynamic contact angle (DCA) technique, using several reference solutions having the surface tension values between 20-72 mN/m. Measurements of the water intrusion pressure (WIP) of the treated samples were also performed. Surface modifications on the plasma treated meshes were investigated by means of Fourier-transform infrared absorption spectroscopy (FT-IR) and X-ray photoelectron spectroscopy (XPS) analysis. SF(6) and HMDSO plasma treatments decrease the surface energy of the PET meshes, lowering the liquid surface tension at which the wettable/unwettable transition occurs and increasing the WIP. Moreover, an increase in hydrophobic performances was achieved with HMDSO plasma polymerisation followed by SF(6) plasma treatment.


Automated classification of cyclic alternating pattern sleep phases in healthy and sleep-disordered subjects using convolutional neural network.
Sleep contributes to more than a third of a person's life, making sleep monitoring essential for overall well-being. Cyclic alternating patterns (CAP) are crucial in monitoring sleep quality and associated illnesses such as insomnia, nocturnal frontal lobe epilepsy (NFLE), narcolepsy, etc. However, traditionally medical specialists practice manual division techniques of CAP phases which are sensitive to human weariness and inaccuracies. This might result in a false sleep stage diagnosis. This study proposes an automated approach using a deep learning model based on a 1-dimensional convolutional neural network for classifying CAP phases (A and B). The proposed model uses single-channel standardized electroencephalogram (EEG) recordings provided by the CAP sleep database. The model was created with the help of healthy participants and patients suffering from five distinct sleep disorders, which includes narcolepsy, rapid eye movement behaviour disorder (RBD), periodic leg movement disorder (PLM), NFLE, and insomnia. The developed model has achieved the highest automated classification accuracy of 78.84% for the healthy dataset and 82.21%, 79.48%, 78.73%, 76.68%, and 70.88% for narcolepsy, RBD, PLM, NFLE, and insomnia subjects, respectively in categorizing phases A and B. The proposed approach can help medical professionals monitor sleep and examine a person's brain stability.


Low Serum Levels of 25-Hydroxyvitamin D Are Associated with Stroke Recurrence and Poor Functional Outcomes in Patients with Ischemic Stroke.
To evaluate the association between serum 25(OH) D levels and functional outcome and stroke recurrence events in a 6-month follow-up study in a cohort of patients with an acute ischemic stroke (AIS). From March 2014 to August 2015, consecutive first-ever AIS patients admitted to the Department of Emergency of our hospital were identified. Serum 25(OH) D levels were measured at admission. Functional outcome was evaluated at 6-month using the modified Rankin scale (m-Rankin). We used logistic regression models to assess the relationship between 25(OH) levels and risk of recurrent stroke or functional outcome. We recorded 277 stroke patients. There were significantly negative correlation between levels of 25(OH) D and NHISS (P<0.001), and the infarct volume (P< 0.001). Thirty-one patients (11.9%) had a stroke recurrence, while 82 patients (29.6) were with poor functional outcomes. In multivariate logistic regression analyses, serum 25(OH) D level was an independent marker of poor functional outcome and stroke recurrence [odds ratio (OR) 2.55 (1.38-3.96) and 3.03(1.65-4.12), respectively, P<0.001 for both, adjusted for NHISS, other predictors and vascular risk factors] in patients with AIS. Our results demonstrate that low 25(OH) D levels are associated with stroke recurrence and support the hypothesis that 25(OH) D may serve as a biomarker of poor functional outcome after stroke.


Direct and indirect toxic effects of cotton-derived cellulose nanofibres on filamentous green algae.
Recently, cellulose nanofibers (CNFs) have attracted considerable attention as natural, abundant polymers with excellent mechanical properties and biodegradability. CNFs provide a new materials platform for the sustainable production of high-performance nano-enable products for various applications. Given the increasing rates of CNF production, the potential for their release to the environment and the subsequent impact on ecosystem is becoming an increasing concern that needs to be addressed. Here, we used the Klebsormidium flaccidum as a bioindicator organism of terrestrial and freshwater habitats pollution using a battery of biomarkers. Our results show that cotton CNFs inhibit the proliferation of algae and induce morphological changes in them. The two main toxicity mechanisms induced by cotton CNFs are: (i) a direct contact of CNFs with the cell wall and cellular membrane and (ii) an indirect effect through the generation of reactive oxygen species (ROS).


Exenatide inhibits necrosis by enhancing angiogenesis and ameliorating ischemia/reperfusion injury in a random skin flap rat model.
Random skin flaps are often used for plastic repair because they are convenient and flexible. However, necrosis of flaps is a common complication that may lead to disastrous consequences. Exenatide, a glucagon-like peptide 1 receptor agonist, can enhance angiogenesis and ameliorate ischemia/reperfusion injury. Our experiments explored random skin flap outcomes after its use. We established modified dorsal McFarlane flaps on 54 Sprague-Dawley rats and divided the rats into three groups (control, Exe-I, and Exe-II). We intraperitoneally injected either 4 or 8 μg/kg/day exenatide into the rats of the Exe-I and Exe-II groups, respectively. On the seventh day after the operation, we measured the levels of superoxide dismutase (SOD) and malondialdehyde (MDA). Tissue sections were obtained for histopathological and immunohistochemical analyses, and we evaluated the expression of vascular endothelial growth factor (VEGF), interleukin (IL) 6, IL-1β, nuclear factor kappa beta (NF-κB), Toll-like receptor 4 (TLR4), and tumor necrosis factor α (TNF-α). We measured blood flow reconstruction and angiogenesis using laser Doppler blood flowmetry and lead oxide/gelatin angiography, respectively. Exenatide increased the average survival area of the flap and improved microvascular density and blood flow intensity in a dose-dependent manner. Meanwhile, the SOD level was up-regulated and the MDA level down-regulated. Exenatide also enhanced the expression of VEGF and reduced the expression of inflammatory cytokines (IL-6, IL-1β, NF-κB, TLR4, and TNF-α), thereby promoting angiogenesis and inhibiting inflammation. Exenatide potentially inhibits necrosis in our rat random skin flap model.


AIR KERMA TO Hp(3) CONVERSION COEFFICIENTS FOR IEC 61267 RQR X-RAY RADIATION QUALITIES: APPLICATION TO DOSE MONITORING OF THE LENS OF THE EYE IN MEDICAL DIAGNOSTICS.
Recent studies highlight the fact that the new eye lens dose limit can be exceeded in interventional radiology procedures and that eye lens monitoring could be required for these workers. The recommended operational quantity for monitoring of eye lens exposure is the personal dose equivalent at 3 mm depth Hp(3) (ICRU 51). However, there are no available conversion coefficients in international standards, while in the literature coefficients have only been calculated for monoenergetic beams and for ISO 4037-1 X-ray qualities. The aim of this article is to provide air kerma to Hp(3) conversion coefficients for a cylindrical phantom made of ICRU-4 elements tissue-equivalent material for RQR radiation qualities (IEC-61267) from 40 to 120 kV and for angles of incidence from 0 to 180°, which are characteristic of medical workplace. Analytic calculations using interpolation techniques and Monte Carlo modelling have been compared.


Corneal Biomechanical and Anterior Chamber Parameters Variations after 1-year of Transepithelial Corneal Collagen Cross-linking in Eyes of Children with Keratoconus.
To assess the changes in corneal hysteresis (CH) and corneal resistance factor (CRF) 1-year following transepithelial corneal collagen cross-linking (CXL) treatment in eyes of children with keratoconus. This case series was conducted in 22 eyes of 22 children. Children aged < 18 years with progressive keratoconus were included. They were treated with transepithelial CXL. Corneal biomechanical and anterior chamber parameters such as CH, CRF, and peak 1 were noted using ocular response analyzer, Pentacam, intraocular lens master, and anterior segment optical coherence tomography before and 1, 3, 6, and 12 months after treatment. Our series had 22 eyes of 22 children with a mean age 15.7 ± 2.1 years. The CH and CRF 1-year after treatment declined (difference of mean 0.1 mmHg (95% confidence interval [CI] 0.04-0.24), P = 0.2] and (difference of mean 0.1 mmHg [95% CI 0.04-0.30], P = 0.3), respectively. Peak 1 and peak 2 increased (difference of mean 0.1 mmHg [95% CI 0.006-0.008], P = 0.2) and (difference of mean 0.1 mmHg [95% CI 0.007-0.006], P = 0.3), respectively. The uncorrected distance visual acuity improved from 0.95 ± 0.34 logMAR to 0.68 ± 0.45 logMAR (P < 0.05). No statistically significant changes during 12 months follow-up were observed in axial length, corneal volume, anterior chamber volume, and anterior chamber depth (P > 0.05). Transepithelial CXL in keratoconus in pediatric age group seems to have good stability in corneal biomechanical parameters after 1-year. Further studies with a larger sample and better study design are recommended to confirm our findings.


The electron transfer reactivity of kaempferol and its interaction with amino acid residues.
In this work, the electron transfer reactivity of kaempferol was studied and the interaction in vivo between kaempferol and protein was simulated. Dimethylsulfoxide (DMSO) as an aprotic solvent was employed to simulate the specific environment. Various residues of amino acids were used to study the effect of the amino acids in the active site of protein on the electron transfer reactivity of kaempferol. Experimental results revealed that the redox activity of kaempferol was different in aprotic medium DMSO from that in water, and a new redox process was further found. Of all the residues tested, nitrogenous nucleophile, for example, imidazole, was observed to be able to facilitate the electron transfer of kaempferol, and the mechanism was also proposed. This work might provide a simple model to study the electron transfer reactivity of some small active organic molecules, especially medicines, in specific environment, which might approach a more accurate understanding of the activity of some medicines in vivo.


[Analysis of death cases involved in TASER in the State of Maryland].
To evaluate the features of autopsy cases involved in electronic weapon (TASER) in the State of Maryland, and to discuss the appraisable points. Thirteen autopsy cases involving TASER were collected from 2004 to 2011 in the Office of the Chief Medical Examiner, State of Maryland. All the cases include detailed scene investigations, complete autopsy, toxicological analysis and histopathological examination. Statistical analysis were conducted including general information of victim, type of TASER, type of contact, toxicological results, manner and cause of death. Majority of victims were male with an acute onset of agitated and delusional behavior. Drugs were often involved. Deaths were attributed to multiple factors. Most of cases involved in TASER resulted from multiple fatal factors. Further researches are needed for the principal mechanism. Thorough scene investigation and complete autopsy examination play crucial role in evaluation of such cases.


Transient global amnesia in a patient with high and persistent levels of antiphospholipid antibodies.
Cerebrovascular disease is one of the most common symptoms associated with anticardiolipin antibodies (ACA) and lupus anticoagulant (LA), usually in the form of ischemic stroke. However, many other neurologic disorders have been described in patients with antiphospholipid syndrome or ACA. So far, the precise relation between the presence of antibodies and the development of the disease in many of these cases remain unknown. Transient global amnesia (TGA) is an infrequent neurologic disturbance whose precise pathophysiology is not known. It is characterized by a sudden inability to acquire new information, usually lasting no more than 12 h, and it is not accompanied by any other focal neurological signs or symptoms. We report a patient with TGA with persistent and high levels of ACA and LA and suggest that in patients with TGA, investigation of the possible presence of ACA and/or LA may be warranted because a higher prevalence of TGA in the patients with antiphospholipidic syndrome with respect to the general population may lead to further insights into pathogenesis of neurologic disease associated with antiphospholipidic antibodies.


Synthesis and automated fluorine-18 radiolabeling of new PSMA-617 derivatives with a CuAAC radiosynthetic approach.
In the last decade, the development of new radiopharmaceuticals for the imaging and therapy of prostate cancer has been a highly active and important area of research, especially focusing on the prostate-specific membrane antigen (PSMA), an antigen which is upregulated in prostate, as well as in other tumor cells. A large variety of PSMA ligands have been radiolabeled, to date. Among the various derivatives, PSMA-617 resulted to be one of the most interesting in terms of interaction with the antigen and clinical properties, and its lutetium-177 labeled version has recently been approved by regulatory agencies for therapeutic purposes. For this reasons, the radiolabeling with fluorine-18 of a PSMA-617 derivative might be of interest. Beside other methodologies to radiolabel macromolecules with fluorine-18, the "click-chemistry" approach resulted to be very useful, and the copper-catalyzed azide-alkyne cycloaddition (CuAAC) is considered one of most efficient and reliable. This paper proposes the synthesis of a suitable precursor for the radiolabeling with fluorine-18 of a new PSMA-617 derivative. The whole radiosynthetic procedure has been fully automated, and the final product, which proved to be stable in plasma, has been obtained with radiochemical yield and purity suitable for subsequent preclinical studies.


Chemical synthesis of idiotopes. Evidence that antisera to the same JH1 peptide detect multiple binding site-associated idiotopes.
In an attempt to better understand the molecular basis of idiotypy, we have generated several site-specific antisera through immunization of animals with synthetic peptides corresponding to the (JH1) heavy chain joining segment 1 of the mouse heavy chain variable (VH) region. These anti-peptide sera identify several idiotypic determinants present on intact hybridoma and myeloma immunoglobulins. Expression of at least three of these idiotopes is correlated with the antigen specificity of the family of immunoglobulins bearing the determinant. Use of synthetic peptides may prove a powerful technique in the generation of molecularly defined antiidiotypic reagents.


Diffusion characteristics of alginate membranes.
The diffusive properties of alginate membranes prepared by the interfacial reaction of sodium alginate solution with gypsum substrates were studied. The penetrants of primary importance for the above study were methyl methacrylate (MMA) and water, since alginate membranes are used as mould release agents, during the casting of poly(methyl methacrylate) (PMMA) in gypsum moulds in a water bath. Vapour sorption measurements were carried out at various temperatures. The effect of temperature and the combined action of water and MMA on the swelling behaviour of the membrane was also investigated. The results indicate that the water sorption of alginate membranes is non-Fickian, in spite of the linearity of the curves obtained by plotting Mt/M infinity versus t 1/2, at least for a short time period. The membrane treatment with methyl methacrylate, leads to considerably lower equilibrium sorption, possibly because of the formation of a thin film of poly(methyl methacrylate) on the membrane surface.


Expanding the role of the ureteroscope.
Although the rigid ureteroscope was designed exclusively for the diagnosis and treatment of pathological conditions of the ureter, its smaller diameter and extended length allow for its increased use in endoscopic procedures that cannot be performed successfully with a cystoscope. The indications can be divided into 3 categories: 1) difficult ureteral catheterizations, 2) augmented bladders and diverticula, and 3) narrow, strictured urethras and bladder necks. Several cases from each category are presented to illustrate the expanded role of the rigid ureteroscope in daily urological practice.


Sleep and growth hormone secretion in women athletes.
Six women athletes underwent 24 h multiple sampling studies with electroencephalographic monitoring of sleep for the assessment of growth hormone secretion and sleep pattern. The athletes tended to have more stage 4 sleep, less REM activity and a similar REM density compared to 5 normal women. The nocturnal secretion of growth hormone was elevated in the first hour following sleep onset in the athletes but was otherwise not statistically different from that of the controls. As all but one of the women athletes had exercise-related menstrual irregularities, the findings reported may be associated with exercise amenorrhea.


The structural components of the Azotobacter vinelandii iron-only nitrogenase, AnfDKG, form a protein complex within the plant mitochondrial matrix.
A long-held goal of synthetic biology has been the transfer of a bacterial nitrogen-fixation pathway into plants to reduce the use of chemical fertiliser on crops such as rice, wheat and maize. There are three classes of bacterial nitrogenase, named after their metal requirements, containing either a MoFe-, VFe- or FeFe-cofactor, that converts N2 gas to ammonia. Relative to the Mo-nitrogenase the Fe-nitrogenase is not as efficient for catalysis but has less complex genetic and metallocluster requirements, features that may be preferable for engineering into crops. Here we report the successful targeting of bacterial Fe-nitrogenase proteins, AnfD, AnfK, AnfG and AnfH, to plant mitochondria. When expressed as a single protein AnfD was mostly insoluble in plant mitochondria, but coexpression of AnfD with AnfK improved its solubility. Using affinity-based purification of mitochondrially expressed AnfK or AnfG we were able to demonstrate a strong interaction of AnfD with AnfK and a weaker interaction of AnfG with AnfDK. This work establishes that the structural components of the Fe-nitrogenase can be engineered into plant mitochondria and form a complex, which will be a requirement for function. This report outlines the first use of Fe-nitrogenase proteins within a plant as a preliminary step towards engineering an alternative nitrogenase into crops.


Fine structure of the gills of some Indian air-breathing fishes.
A detailed account is given of the structure of the gills of Clarias batrachus, Heteropneustes (= Saccobranchus) fossilis, Channa punctata, Monopterus (= Amphipnous) cuchia and Boleophthalmus boddaerti, based upon light and electron microscopy. In all five species the basic organization into primary and secondary lamellae is apparent but the latter are very much more modified in Monopterus. Three main layers separate the water and blood on the surface of the secondary lamellae. The outer epithelium is usually two layered but may be multilayered close to the origin of the secondary lamellae from the gill filament. The basement membrane is relatively thin and a middle dense layer containing collagen fibrils separates two clear layers. The pillar cells, so characteristic of secondary lamellae, are present in all except Monopterus and flanges from these cells surround the blood channels with the exception of the marginal channels. The latter are lined by endothelial cells which line all the blood channels of Monopterus. The overall thickness of the three layers comprising the water/blood barrier ranges from 1.5 to 13 microns. A number of modifications to this basic organization can be related to the degree of dependence of the different species on air-breathing. Boleophthalmus is the only species commonly found in brackish water and its secondary lamellae have well developed lymphoid spaces between two layers of the epithelium. Special densely-stained regions of the pillar cell flanges were also present in this fish and may have a supporting function.


[THE ROLE OF ENDOSCOPIC MAMMODUCTOSCOPY IN COMPLEX DIAGNOSIS OF INTRADUCTAL TUMORS OF MAMMARY GLAND].
First Ukrainian experience in endoscopic mammoductoscopy (EMDS) conduction in 112 patients for revealing of intraductal tumors of mammary gland is presented. In comparison with roentgenological, ultrasonographic and cytological diagnostical methods, EMDS for intraductal tumors of mammary gland differs by highest sensitivity (90.3%) and accuracy (80.2%), but insufficient (47.4%) specificity. To improve the surgical treatment results the authors propose their own method of marking of the mammary gland intraductal tumors under endoscopic and echographic control.


Synchronous bilateral renal cell carcinomas with differing histologies.
Bilateral renal cell carcinomas with different histological types are rare. We report herein the first description of bilateral renal carcinomas with clear cell renal cell carcinoma and mucinous tubular and spindle cell carcinoma occurring synchronously. A 62-year-old man was referred to our hospital with bilateral renal tumors. The tumors on each side showed different findings from both contrast-enhanced computed tomography and magnetic resonance imaging. The tumors were partially resected. Histopathological and immunohistochemical examination of the left renal tumor diagnosed clear cell renal carcinoma. Histopathological and immunohistochemical examination of the right renal tumor diagnosed mucinous tubular and spindle cell carcinoma. We encountered a case with clear cell renal cell carcinoma and mucinous tubular and spindle cell carcinoma occurring simultaneously in bilateral kidneys.


Competitive dual-strain SIS epidemiological models with awareness programs in heterogeneous networks: two modeling approaches.
Epidemic diseases and media campaigns are closely associated with each other. Considering most epidemics have multiple pathogenic strains, in this paper, we take the lead in proposing two multi-strain SIS epidemic models in heterogeneous networks incorporating awareness programs due to media. For the first model, we assume that the transmission rates for strain 1 and strain 2 depend on the level of awareness campaigns. For the second one, we further suppose that awareness divides susceptible population into two different subclasses. After defining the basic reproductive numbers for the whole model and each strain, we obtain the analytical conditions that determine the extinction, coexistence and absolute dominance of two strains. Moreover, we also formulate its optimal control problem and identify an optimal implementation pair of awareness campaigns using optimal control theory. Given the complexity of the second model, we use the numerical simulations to visualize its different types of dynamical behaviors. Through theoretical and numerical analysis of these two models, we discover some new phenomena. For example, during the persistence analysis of the first model, we find that the characteristic polynomials of two boundary equilibria may have a pair of pure imaginary roots, implying that Hopf bifurcation and periodic solutions may appear. Most strikingly, multistability occurs in the second model and the growth rate of awareness programs (triggered by the infection prevalence) has a multistage impact on the final size of two strains. The numerical results suggest that the spread of a two-strain epidemic can be controlled (even be eradicated) by taking the measures of enhancing awareness transmission, reducing memory fading of aware individuals and ensuring high-level influx and rapid growth of awareness programs appropriately.


Intranasal benzo[a]pyrene alters circadian blood pressure patterns and causes lung inflammation in rats.
Polycyclic aromatic hydrocarbons, including benzo[a]pyrene (BaP), are environmental contaminants formed during organic material combustion (e.g. burning fossil fuels and cigarette smoke). BaP toxicity is mediated, in part, by activation of the aryl hydrocarbon receptor and formation of reactive metabolites, both of which lead to increased oxidative stress. Since air pollution and cigarette smoking are known to increase cardiovascular disease in humans, the objective of this study was to determine the effects of 7-day intranasal BaP exposure on circadian blood pressure patterns, arterial stiffness, and possible sources of oxidative stress in radiotelemetry-implanted rats. Arterial pulse wave dP/dt was used an indicator of arterial stiffness and was compared to both functional (nitric oxide production and bioactivity, endothelin-1 levels) and structural (wall thickness) features of the arterial wall. In addition, histology of lung, heart, and liver were examined as well as pulmonary and hepatic cytochrome P450 1A1 (CYP1A1) activity. BaP exposure altered the circadian pattern of blood pressure, with a reduction in the normal dipping pattern during sleep. This was associated with increased neutrophil recruitment in the lungs of BaP-exposed rats. In contrast, BaP had no effect on cardiovascular tissue histology, arterial stiffness, oxidative stress or lung and liver CYP1A1 activity. Thus, the current study does not support the hypothesis that BaP reactive metabolites increase oxidative stress leading to reduced vascular NO bioactivity and increased blood pressure. Instead, the current study suggests that inflammation, detected only in the lung, is associated with altered circadian rhythm of blood pressure.


Ionizing radiation downregulates estradiol synthesis via endoplasmic reticulum stress and inhibits the proliferation of estrogen receptor-positive breast cancer cells.
Breast cancer is a major threat to women's health and estrogen receptor-positive (ER+) breast cancer exhibits the highest incidence among these cancers. As the primary estrogen, estradiol strongly promotes cellular proliferation and radiotherapy, as a standard treatment, exerts an excellent therapeutic effect on ER+ breast cancer. Therefore, we herein wished to explore the mechanism(s) underlying the inhibitory effects of radiation on the proliferation of ER+ breast cancer cells. We used the ER+ breast cancer cell lines MCF7 and T47D, and their complementary tamoxifen-resistant cell lines in our study. The aforementioned cells were irradiated at different doses of X-rays with or without exogenous estradiol. CCK8 and clone-formation assays were used to detect cellular proliferation, enzyme-linked immunosorbent assay (ELISA) to determine estradiol secretion, western immunoblotting analysis and quantitative real-time PCR to evaluate the expression of proteins, and immunofluorescence to track endoplasmic reticulum stress-related processes. Finally, BALB/C tumor-bearing nude mice were irradiated with X-rays to explore the protein expression in tumors using immunohistochemistry. We found that ionizing radiation significantly reduced the phosphorylation of estrogen receptors and the secretion of estradiol by ER+ breast cancer cells. CYP19A (aromatase) is an enzyme located in the endoplasmic reticulum, which plays a critical role in estradiol synthesis (aromatization), and we further demonstrated that ionizing radiation could induce endoplasmic reticulum stress with or without exogenous estradiol supplementation, and that it downregulated the expression of CYP19A through ER-phagy. In addition, ionizing radiation also promoted lysosomal degradation of CYP19A, reduced estradiol synthesis, and inhibited the proliferation of tamoxifen-resistant ER+ breast cancer cells. We concluded that ionizing radiation downregulated the expression of CYP19A and reduced estradiol synthesis by inducing endoplasmic reticulum stress in ER+ breast cancer cells, thereby ultimately inhibiting cellular proliferation.


A peptide-based fluorescent sensor for selective imaging of glutathione in living cells and zebrafish.
Monitoring and imaging glutathione (GSH) in living systems is an essential tool to determine the key roles of GSH in biological pathways, but most fluorescent sensors can only be used in vitro because of their potential biotoxicity. Here, a peptide-based fluorescent sensor, FP, has been successfully designed and synthesized based on the biocompatibility of the peptide backbone and low toxicity. The design strategy of FP contains a specific spatial structure of the peptide sequence which selectively binds to Cu2+, triggering fluorescence quenching. Interestingly, the fluorescence of FP can be fully restored by GSH, due to the strong binding between Cu2+ and the GSH sulfhydryl groups. Finally, the sensor is highly sensitive and selective for imaging GSH both in vitro and in vivo with low toxicity. Thus, FP with its strong "on-off-on" fluorescence changes is a powerful way to image GSH both in cells and zebrafish larvae to study the GSH pathway.


General theory of cell regulation.
A general theory of cell regulation has been based on a previously described concept that both DNA chains of the chromatin may be expressed, and the protein products of this type of gene expression are also complementary to each other and can specifically interact with each other and with the nucleic acids which serve the code for them. The regulation of biological processes is directed by these specifically interacting molecules which are organized in Elementary Regulatory Units (ERU). The biological information in ERUs is persisting reversibly transformable (on the basis of protein and nucleic acid complementarity), buffered, and complementary information is in balance with each other. The information transfer by macromolecules in the ERUs follows the law of mass action. Biologically active "small" molecules (nucleotide phosphates, steroids, iodothyronins) interact with the ERUs and influence their steady states. The contact inhibition of the cells and the cooperative regulation of different cells and cell functions have been explained on the basis of the theoretically explained properties of the ERUs.


Changes in endolymphatic hydrops after vestibular neurectomy observed in magnetic resonance imaging - A pilot study.
The aim was to evaluate endolymphatic hydrops in patients with Ménière's disease before and after vestibular neurectomy to verify if the endolymphatic space dilatation, observed in magnetic resonance imaging, regressed within several months after surgery. Magnetic resonance imaging was performed after intravenous gadolinium injection in four patients with unilateral definite Ménière's disease before and eight months after vestibular neurectomy. Clinical symptoms, audiovestibular tests, and endolymphatic hydrops in magnetic resonance imaging were evaluated. Endolymphatic hydrops was visualized in preoperative magnetic resonance imaging in three out of four analyzed patients. In the remaining one, an asymmetrical contrast enhancement in the affected ear was found. After the vestibular neurectomy, all four patients presented a complete resolution of vertigo episodes and improved functional level. Significant postoperative hearing deterioration was found in two patients. In the follow-up magnetic resonance imaging, no reduction of the endolymphatic hydrops was visualized. A reduction of asymmetrical contrast enhancement in one patient was found. Magnetic resonance imaging of the inner ear is a helpful diagnostic tool for Menière's disease. Vestibular neurectomy is an effective treatment for intractable vertigo; however, there is no endolymphatic hydrops regression evidence within several months after the surgery. Therefore, further studies with a long follow-up period and repeated magnetic resonance imaging are needed to assess the vestibular neurectomy's impact on endolymphatic hydrops. Nevertheless, magnetic resonance imaging supports the clinical diagnosis of Ménière's disease and may help understand its pathophysiology.


Technical Note: Patient-weight dependence of the effective dose conversion coefficients for diagnostic x-ray imaging procedures.
The aim of this study was to provide a method and reference data for the evaluation of the weight dependence of the conversion coefficients from air collision kerma integrated over beam area to the effective dose for patients undergoing diagnostic x-ray examinations. A simple physics-based analytical model was developed in order to calculate the weight dependence of the effective dose conversion coefficients based on existing values of the conversion coefficients between patient effective dose and air collision kerma integrated over beam area calculated by the Monte Carlo method on the base of computational MIRD-5-type stylized models. The analytical expressions that make possible taking into account a patient's weight when assessing the effective dose were presented. The following categories of diagnostic x-ray examinations are considered: CT; plain radiography; cardiac angiography; fluoroscopy. The results indicate that the weight dependence of the effective dose conversion coefficients for different categories of diagnostic x-ray examinations has the same form. Correction factor for evaluation of the new value of the effective dose conversion coefficient for a patient with weight Wpa. when we know its value for a standard patient with weight Wst. depends on the ratios of their weights (Wst. /Wpat. ) and fractions of the incident energy which is imparted to a patient. The paper presents an approach and necessary data for the estimation of the weight dependence of the effective dose conversion coefficients for patients undergoing different diagnostic x-ray examinations.


MiR-142-3p as an Indicator of OSA Severity Predicts Prognosis in Lung Adenocarcinoma with OSA.
The aim was to explore the correlation between Obstructive sleep apnea (OSA) and Lung adenocarcinoma malignant prognosis and evaluate the miR-142-3p was used as an OSA severity indicator to predict the prognosis of Lung adenocarcinoma patients. This study comprised of 21 diagnosed lung adenocarcinoma patients with or without OSA. The sleep-related variables and tumor pathology were recorded. Hypoxia-inducible factor-1α (HIF1α) and ki67 expression were analyzed by immunohistochemistry in tumor samples. Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to assess the level of miR-142-3p. Lung adenocarcinoma with OSA showed higher apnea-hypopnea index (AHI), oxygen desaturation index (ODI), and the lower lowest pulse oxygen saturation (LSPO2) compared to Lung adenocarcinoma without OSA (P<0.05), and patients with severer OSA have an advanced TNM stage (P=0.004) and metastasis rate (p=0.032). In addition, OSA may down-regulate the miR-142-3p expression in patients with Lung adenocarcinoma, and the patients with low miR-142-3p expression exhibited severe OSA. MiR-142-3p levels significantly decreased in the advanced TNM stage (p=0.015), and the expression of miR-142-3p was negatively associated with AHI (r= -0.505, p=0.020), ODI (r= -0.513, p=0.017). OSA severity may increase Lung adenocarcinoma malignant prognosis. OSA may down-regulate the expression of miR-42-3p. The expression of miR-142-3p was inversely correlated with AHI and ODI as a surrogate of OSA severity. Additionally, the low miR-142-3p expression level was significantly associated with advanced TNM stage in Lung adenocarcinoma patients.


Yeast mitochondrial calcium uptake: regulation by polyamines and magnesium ions.
Spermine, spermidine, and magnesium ions modulate the kinetic parameters of the Ca2+ transport system of Endomyces magnusii mitochondria. Mg2+ at concentrations up to 5 mM partially inhibits Ca2+ transport with a half-maximal inhibiting concentration of approximately 0.5 mM. In the presence of 2 mM MgCl2, the S0.5 value of the Ca2+ transport system increases from 220 to 490 microM, which indicates decreased affinity for the system. Spermine and spermidine exert an activating effect, having half-maximal concentrations of 12 and 50 microM, respectively. In the case of spermine, the S0.5 value falls to 50-65 microM, which implies an increase in the transport system affinity for Ca2+. Both Mg2+ and spermine cause a decrease of the Hill coefficient, giving evidence for a smaller degree of cooperativity. Spermine and spermidine enable yeast mitochondria to remove Ca2+ from the media completely. In contrast, Mg2+ lowers the mitochondrial buffer capacity. When both Mg2+ and spermine are present in the medium, their effects on the S0.5 value and the free extramitochondrial Ca2+ concentration are additive. The ability of spermine and Mg2+ to regulate yeast mitochondrial Ca2+ transport is discussed.


Interleukin-6 response to insulin-induced hypoglycemia is associated with hypothalamic-pituitary-adrenal axis activation.
Increased plasma levels of interleukin-6 (IL-6) in response to acute hypoglycemia have been well documented. Aiming to study the interaction between IL-6 and counter-regulatory hormones during hypoglycemic stress we conducted an exploratory single center study involving 26 adult patients undergoing insulin tolerance test. Insulin-induced hypoglycemia elicited a significant dynamic response of IL-6, adrenaline, noradrenaline, GH, prolactin, ACTH and serum and salivary cortisol (P < 0.001 for all variables). Patients with insufficient HPA axis response had lower hypoglycemia-induced IL-6 increase (median: 0.88 pg/mL) compared with individuals with intact HPA axis response (2.03 pg/mL, P = 0.007). IL-6 maximal increase correlated with the maximal increase of serum cortisol (rs = 0.48; P = 0.013), salivary cortisol (rs = 0.66; P = 0.012), plasma ACTH (rs = 0.48; P = 0.013) and with the increase in procedure-related symptoms of anxiety and hypoglycemia (rs = 0.57; P = 0.003). In conclusion, hypoglycemic stress-induced IL-6 increase is associated with activation of the HPA axis, suggesting that IL-6 response to hypoglycemic stress may be regarded as part of the counter-regulatory response, possibly contributing to the maintenance of glucose homeostasis.


A case of renal cell carcinoma after successful treatment of Wilms tumor.
This case report documents the eighth reported case of renal cell carcinoma (RCC) occurring after treatment of Wilms tumor. Although secondary malignancies after treatment of Wilms tumors are not infrequent, RCC as the second malignancy is rare. We discuss a 17-year-old girl whose RCC was diagnosed 12.5 years after diagnosis of a Wilms tumor. In addition, we review the literature on the subject. Renal cell carcinoma has been proposed as a consequent of chemoradiation; however, a genetic susceptibility must be considered. Because it is routine to assess the functional status of the remaining solitary kidney by annual ultrasonography, we recommend assessing for the presence of secondary renal malignancies and perhaps continuing routine ultrasounds long-term.


Monostotic Paget's disease involving the calcaneus encountered incidentally on bone scintigraphy.
Isolated involvement of calcaneus with Paget's disease of bone is highly unusual, with very few cases reported in the world literature. We present herein a unique 69-year-old male patient with monostotic Paget's disease of the left calcaneus discovered incidentally during a whole body bone scintigraphy. Since most bone scans are performed for evaluating osseous metastases, differentiating Paget's disease from overlapping metastases may be of significant clinical value. We discuss further the importance of whole body bone scan and other imaging modalities in establishing the correct diagnoses in such cases.


[Decrease in toxicity and therapeutic effect of zoledronic acid in combination therapy with different antioxidant extracts].
Zoledronic acid is used in the treatment of cancer-related diseases, although its use has been associated with avascular osteonecrosis. To determine the possible protective effect of a range of antioxidant substances against the inhibition of human prostate epithelial cell growth (PNT2) and transgenic adenocarcinoma mouse prostate tumour cells (TRAMP-C1), in treatments combining zoledronic acid and ionising radiation (IR). Cell survival is studied via cell viability assays (MTT) for 2 cell lines in isolated and combined treatments with zoledronic acid and/or IR, as well as the effect of adding 3 antioxidant substances. Zoledronic acid displays a significant cytotoxic effect over PNT2 and TRAMP-C1 cells (P<.001). The administration of antioxidants together with the zoledronic acid shows a protective effect for normal prostate cells, yet not so for prostate tumour cells. However, the administration of rosmarinic acid and apigenin in treatments combined with zoledronic acid provides a protective effect from the harmful effects of applying ionizing radiation, not only for normal PNT2 cells, but also for tumour cells. The use of antioxidant substances decreases the cytotoxic effect of zoledronic acid over non-tumour cells, and as such could be used in benign diseases. Furthermore, in the combined treatment using ionising radiation, these antioxidants also produced a protective effect in tumour cells, thus reducing the therapeutic effect sought by combining the treatment with radiation.


Reactivation of Chagas Disease: Implications for Global Health.
Reactivation of Chagas Disease (CD) is a global public health issue. Reactivation of disease can affect the management of CD and its clinical outcome, adding pressure to global health systems because it exacerbates symptoms, leading to misdiagnosis and delays in the administration of correct treatments. Concurrent infections complicate the issue of reactivation, because there are various parasites and disease treatment regimens that are able to influence or suppress the immune system of the host, reactivating disease within infected individuals. The effect of delayed symptoms of chronic CD and the potential for disease reactivation are of great importance to nonendemic regions of the world, where knowledge about CD is lacking and the potential for vectorial transmission is not known.


Histone Modifications: Insights into Their Influence on Gene Expression.
This year's Albert Lasker Basic Medical Research Award honors David Allis and Michael Grunstein for their pioneering research that highlighted the importance of histones and their post-translational modifications in the direct control of gene expression.


Changes in Drosophila mitochondrial proteins following chaperone-mediated lifespan extension confirm a role of Hsp22 in mitochondrial UPR and reveal a mitochondrial localization for cathepsin D.
Hsp22 is a small mitochondrial heat shock protein (sHSP) preferentially up-regulated during aging in Drosophila melanogaster. Its developmental expression is strictly regulated and it is rapidly induced in conditions of stress. Hsp22 is one of the few sHSP to be localized inside mitochondria, and is the first sHSP to be involved in the mitochondrial unfolding protein response (UPR(MT)) together with Hsp60, mitochondrial Hsp70 and TRAP1. The UPR(MT) is a pro-longevity mechanism, and interestingly Hsp22 over-expression by-itself increases lifespan and resistance to stress. To unveil the effect of Hsp22 on the mitochondrial proteome, comparative IEF/SDS polyacrylamide 2D gels were done on mitochondria from Hsp22+ flies and controls. Among the proteins influenced by Hsp22 expression were proteins from the electron transport chain (ETC), the TCA cycle and mitochondrial Hsp70. Hsp22 co-migrates with ETC components and its over-expression is associated with an increase in mitochondrial protease activity. Interestingly, the only protease that showed significant changes upon Hsp22 over-expression in the comparative IEF/SDS-PAGE analysis was cathepsin D, which is localized in mitochondria in addition to lysosome in D. melanogaster as evidenced by cellular fractionation. Together the results are consistent with a role of Hsp22 in the UPR(MT) and in mitochondrial proteostasis.


The insulin concentration in human ocular fluids.
We measured immunoreactive insulin concentrations in ocular fluids and serum of 19 patients. In rhegmatogenous retinal detachment patients without diabetes mellitus, the serum insulin level was 7 +/- 2 (SE) microunits/ml and the subretinal fluid insulin levels were mostly undetectable. By contrast, in rhegmatogenous retinal detachment patients with diabetes mellitus, serum insulin was 35 +/- 5 microunits/ml and the subretinal fluid always contained low but detectable amojnts of insulin. The data may suggest a small leak of insulin into the subretinal fluid of rhegmatogenous retinal detachment patients with diabetic retinopathy. In vitrectomy patients with diabetes mellitus there was no insulin in the vitreous in eight out of nine cases.


Impaired short-term plasticity in mossy fiber synapses caused by mitochondrial dysfunction of dentate granule cells is the earliest synaptic deficit in a mouse model of Alzheimer's disease.
Alzheimer's disease (AD) in the early stages is characterized by memory impairment, which may be attributable to synaptic dysfunction. Oxidative stress, mitochondrial dysfunction, and Ca²⁺ dysregulation are key factors in the pathogenesis of AD, but the causal relationship between these factors and synaptic dysfunction is not clearly understood. We found that in the hippocampus of an AD mouse model (Tg2576), mitochondrial Ca²⁺ handling in dentate granule cells was impaired as early as the second postnatal month, and this Ca²⁺ dysregulation caused an impairment of post-tetanic potentiation in mossy fiber-CA3 synapses. The alteration of cellular Ca²⁺ clearance in Tg2576 mice is region-specific within hippocampus because in another region, CA1 pyramidal neuron, no significant difference in Ca²⁺ clearance was detected between wild-type and Tg2576 mice at this early stage. Impairment of mitochondrial Ca²⁺ uptake was associated with increased mitochondrial reactive oxygen species and depolarization of mitochondrial membrane potential. Mitochondrial dysfunctions in dentate granule cells and impairment of post-tetanic potentiation in mossy fiber-CA3 synapses were fully restored when brain slices obtained from Tg2576 were pretreated with antioxidant, suggesting that mitochondrial oxidative stress initiates other dysfunctions. Reversibility of early dysfunctions by antioxidants at the preclinical stage of AD highlights the importance of early diagnosis and antioxidant therapy to delay or prevent the disease processes.


Essential fatty acids (EFA) deficiency and liver mitochondria.
2 dietary fats, namely, hydrogenated coconut oil and safflower seed oil were fed at 20% levels to weanling male albino rats for a period of 2 months after which the animals were sacrificed and oxidative phosphorylation measured in liver mitochondria. This ratio was more in the unsaturated-fat-fed group of rats compared to the saturated-fed ones for glutamate and malate; in the case of succinate no such change was noticed.


Commentary: Statistical significance and clinical significance - A call to consider patient reported outcome measures, effect size, confidence interval and minimal clinically important difference (MCID).
In healthcare research an intervention may be statistically significant based on quantitative analysis; however, simultaneously it may be relatively insignificant to the health or quality of life of patients affected by a particular condition or disease being treated by the intervention - thus may be interpreted as having low clinical significance. An understanding of statistics is fundamental for evidence informed healthcare. Patient-reported outcome measures (PROMs) direct patients to evaluate aspects of their own health, including quality of life, disability and function. Data obtained from PROMs can be used to demonstrate the impact of healthcare interventions on these elements of a person's quality of life. To interpret outcome measure data for clinical decision making, a clinician must understand the concepts of statistical significance and clinical significance. This commentary explores the concepts of patient reported outcome measures (PROMs), their statistical and clinical significance, and explores their relationship with a practical example for the clinician. Limitations of research that only reports p-values and the need to consider effect size, confidence intervals, and minimal clinically important difference are also discussed. Together, these concepts can assist the clinician to evaluate whether an intervention may be suitable for their clinical practice.


Molecular and clinical characterization of H3 K27M-mutant "non-midline" glioblastoma: A case report and literature review.
The WHO classification of tumors of the CNS in 2016 defined "diffuse midline glioma, H3 K27M-mutant" as a new tumor entity locating in the CNS midline. However, the H3 K27M-mutation in "non-midline" glioblastoma are rare and their characteristics have been rarely reported. A 16-year-old girl presented a hyper-intense lesion at her left temporal stem on T2WI, FLAIR and DWI. Biopsy was performed and molecular pathological diagnosis was glioblastoma with H3 K27M-mutant. Accordingly, the possibility of H3 K27M-mutant should be examined not only for diffuse glioma without IDH mutation that develops at a midline location, but also in non-midline locations.


Novel index, neutrophil percentage (%) is a useful marker for disease activity in MOG antibody-associated disease.
Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is a CNS autoimmune disease affecting the brain, spinal cord, and optic nerve. The neutrophil-to-lymphocyte ratio (NLR) is related to autoimmune disease activity. However, the clinical implication of index ratios such as the NLR is unclear in patients with MOGAD. We investigated the relationship between index ratios such as the NLR and disease activity and disability to discover the index that best correlates with an attack in MOGAD. Using a CNS demyelinating disease cohort, we reviewed 39 patients with MOGAD (age 37.4 ± 12.0 years; F:M = 20:19) who had 390 blood samples available for cell count analysis. We calculated the NLR, eosinophil-to-lymphocyte-ratio (ELR), platelet-to-lymphocyte-ratio (PLR), monocyte-to-lymphocyte ratio (MLR), basophil-to-lymphocyte ratio (BLR), and neutrophil percentage (N%) [neutrophil count (/mm3) / WBC (/mm3) x 100 (%)]. We investigated the associations between each index ratio and disease activity and disability using the receiver operating characteristic (ROC) curve, machine learning program (kNN algorithm), and generalized estimating equations (GEE) analysis. In patients with MOGAD, the NLR, PLR, and N% were higher and ELR was lower during an attack than in remission (all p<0.001). The areas under the ROC curve for the NLR, ELR, PLR, and N% were 0.68, 0.69, 0.61, and 0.68, respectively, with the highest sensitivity of 76.0% in the ELR and the highest specificity of 76.3% in the N%. The classification accuracy scores of the kNN machine learning algorithm were 71% for the NLR, 62% for the ELR, 63% for the PLR, and 72% for the N%. In the GEE analysis of attack samples, both the NLR and treatment-naive had positive associations with the Expanded Disability Status Scale (EDSS) score (β=0.137, p = 0.008 and β=1.142, p = 0.003, respectively), and the PLR was negatively associated with the EDSS score (β=-0.004, p = 0.022). Our study suggests that the novel index, neutrophil% is the simplest and the most useful marker to differentiate between attack and remission and shows comparable reliability with NLR in MOGAD. Moreover, the NLR and PLR could be used as supportive biomarkers for disease disability during an attack in patients with MOGAD.


Nutrition Trends in Patients Over the Long Term After Kidney Transplantation.
Nutritional behaviors may exert important influence on morbidity and graft function in patients after kidney transplantation (KT). Nutritional status is closely related to potential risk factors of developing posttransplant complications, including diabetes mellitus, weight gain, and negative effects on immunosuppressive therapy. The aim of this study was to assess the dietary intake in patients after KT. Nutritional intake of 154 (61 women and 93 men) patients was assessed based on a questionnaire regarding food intake (proteins, fats, carbohydrates, cholesterol, sugar, phosphorus, calorific value) within 3 working days preceding the routine outpatient posttransplant visit. Patient medical history, concomitant medications, and estimated glomerular filtration rate (eGFR) was obtained from medical charts. The mean age (years) ± SD of patients was 51.9 ± 14.1. The patients were evaluated 94 ± 67 months after KT, with a median eGFR of 53 (range, 41.2-64.1) mL/min/1.73 m2. Sixty-two percent of patients had increased body mass index values. The mean total energy intake was 2159.4 ± 551.9 kcal/day. The patients reported elevated salt (8.5 ± 2.4 g per day) and fat intake (99.4 ± 3.2 g per day) including 57% saturated fatty acids. The patients consumed products containing high amounts of sugars (108.2 ± 107.0 g per day), carbohydrates (238.3 ± 64.3 g per day), and cholesterol (303.6 ± 11.1 mg per day). The diet among kidney recipients consisted predominantly of fats, meat, cured meat, and sweets. The nutritional behaviors of patients after KT are in most cases poor. Improvement of eating habits in these patients seems to be a simple method to preserve kidney function over the long term.


Evaluation of Bacopa monniera for its synergistic activity with rivastigmine in reversing aluminum-induced memory loss and learning deficit in rats.
The objective of this study was to evaluate the synergistic activity of Bacopa monniera with Rivastigmine against aluminum-chloride (AlCl3)-induced cognitive impairment in rats. Adult male Wistar rats were divided into ten groups (n = 10) and subjected to their assigned treatments for 42 days. On the 20(th) day of the respective drug treatments, all the animals were trained in the Morris water maze (retention latency) and the elevated plus maze (transfer latency). After the initial training, the retention latency (RL) and the transfer latency (TL) were evaluated on the 21(st) and the 42(nd) days of the study. Chronic administration of AlCl3 caused significant memory impairment associated with increased RL in the Morris water maze task and increased TL in the elevated plus maze test. Interestingly, animals treated with oral administration of B. monniera (100 and 200 mg/kg), Rivastigmine (5 mg/kg) or a combination of B. monniera (100 mg/kg) with Rivastigmine (5 mg/kg) showed significant protection against AlCl3-induced memory impairment compared to animal treated with AlCl3per se. Additionally, the neuroprotective effect of B. monniera (100 and 200 mg/kg) was significantly improved when supplemented with Rivastigmine (5 mg/kg). These findings suggest that treatment with a combination of B. monniera with Rivastigmine may be highly beneficial compared to their per-se treatment.


Electromechanical coupling of the Kv1.1 voltage-gated K+ channel is fine-tuned by the simplest amino acid residue in the S4-S5 linker.
Investigating the Shaker-related K+ channel Kv1.1, the dysfunction of which is responsible for episodic ataxia 1 (EA1), at the functional and molecular level provides valuable understandings on normal channel dynamics, structural correlates underlying voltage-gating, and disease-causing mechanisms. Most studies focused on apparently functional amino acid residues composing voltage-gated K+ channels, neglecting the simplest ones. Glycine at position 311 of Kv1.1 is highly conserved both evolutionarily and within the Kv channel superfamily, is located in a region functionally relevant (the S4-S5 linker), and results in overt disease when mutated (p.G311D). By mutating the G311 residue to aspartate, we show here that the channel voltage-gating, activation, deactivation, inactivation, and window currents are markedly affected. In silico, modeling shows this glycine residue is strategically placed at one end of the linker helix which must be free to both bend and move past other portions of the protein during the channel's opening and closing. This is befitting of a glycine residue as its small neutral side chain allows for movement unhindered by interaction with any other amino acid. Results presented reveal the crucial importance of a distinct glycine residue, within the S4-S5 linker, in the voltage-dependent electromechanical coupling that control channel gating.


Allosteric Effects of the Proton Donor on the Microbial Proton Pump Proteorhodopsin.
Proteorhodopsin (PR) is a microbial proton pump that is ubiquitous in marine environments and may play an important role in the oceanic carbon cycle. Photoisomerization of the retinal chromophore in PR leads to a series of proton transfers between specific acidic amino acid residues and the Schiff base of retinal, culminating in a proton motive force to facilitate ATP synthesis. The proton donor in a similar retinal protein, bacteriorhodopsin, acts as a latch to allow the influx of bulk water. However, it is unclear if the proton donor in PR, E108, utilizes the same latch mechanism to become internally hydrated. Here, we used molecular dynamics simulations to model the changes in internal hydration of the blue variant of PR during photoactivation with the proton donor in protonated and deprotonated states. We find that there is a stark contrast in the levels of internal hydration of the cytoplasmic half of PR based on the protonation state of E108. Instead of a latch mechanism, deprotonation of E108 acts as a gate, taking advantage of a nearby polar residue (S61) to promote the formation of a stable water wire from bulk cytoplasm to the retinal-binding pocket over hundreds of nanoseconds. No large-scale conformational changes occur in PR over the microsecond timescale. This subtle yet clear difference in the effect of deprotonation of the proton donor in PR may help explain why the photointermediates that involve the proton donor (i.e., M and N states) have timescales that are orders of magnitude different from the archaeal proton pump, bacteriorhodopsin. In general, our study highlights the importance of understanding how structural fluctuations lead to differences in the way that retinal proteins accomplish the same task.


Granulopoiesis in patients with congenital neutropenia.
Granulopoiesis was investigated in five patients with congenital neutropenia (CN) (one Kostmann type, four benign forms). In semisolid agar culture, the marrow cells of all five patients produced normal numbers of CFU-c (colony-forming unit-culture). The size and classification of colonies were normal. In suspension culture in vitro with exogenous colony-stimulating factor (CSF) generated from omental-conditioned medium (OMCM), the myeloid precursors of all patients could proliferate and differentiate into normal polymorphonuclear neutrophils (PMNs). But in the absence of exogenous CSF, myeloid precursors of the patient with Kostmann-type CN did not proliferate or differentiate into PMNs at all. In the four patients with benign neutropenia, however, PMNs were found even without exogenous CSF similar to normal individuals. These results suggest that patients with CN may have normal granulopoietic stem cells with normal proliferative and differentiating capacity in response to exogenous CSF. When a small amount of normal human serum was added to normal marrow cultures stimulated by exogenous CSF, the colony growth increased in a superadditive manner. The enhancing activity of serum from neutropenic patients differed from that of normal serum. Especially, the addition of serum from the patient with Kostmann type CN to normal marrow cultures did not show this enhancement effect. The sera of patients with benign neutropenia had less enhancement effect than did normal control serum. These findings might be interpreted as showing an imbalance between CSF enhancer and inhibitors in the patients' serum.


Rethinking immunologic risk: a retrospective cohort study of severe SARS-CoV-2 infections in individuals with congenital immunodeficiencies.
Debates on the allocation of medical resources during the COVID-19 pandemic revealed the need for a better understanding of immunologic risk. Studies highlighted variable clinical outcomes of SARS-CoV-2 infections in individuals with defects in both adaptive and innate immunity, suggesting additional contributions from other factors. Notably, none of these studies controlled for variables linked with social determinants of health. To determine the contributions of determinants of health to risk of hospitalization for SARS-CoV-2 infection among individuals with inborn errors of immunodeficiencies. This is a retrospective, single-center cohort study of 166 individuals with inborn errors of immunity, aged two months through 69 years, who developed SARS-CoV-2 infections from March 1, 2020 through March 31, 2022. Risks of hospitalization was assessed using a multivariable logistic regression analysis. The risk of SARS-CoV-2-related hospitalization was associated with underrepresented racial and ethnic populations (odds ratio [OR] 5.29; confidence interval [CI], 1.76-17.0), a diagnosis of any genetically-defined immunodeficiency (OR 4.62; CI, 1.60-14.8), use of B cell depleting therapy within one year of infection (OR 6.1; CI, 1.05-38.5), obesity (OR 3.74; CI, 1.17-12.5), and neurologic disease (OR 5.38; CI, 1.61-17.8). COVID-19 vaccination was associated with reduced hospitalization risk (OR 0.52; CI, 0.31-0.81). Defective T cell function, immune-mediated organ dysfunction, and social vulnerability were not associated with increased risk of hospitalization after controlling for covariates. The associations between race, ethnicity, and obesity with increased risk of hospitalization for SARS-CoV-2 infection indicate the importance of variables linked with social determinants of health as immunologic risk factors for individuals with inborn errors of immunity. What is already known about this topic? Outcomes of SARS-CoV-2 infections in individuals with inborn errors of immunity (IEI) are highly variable. Prior studies of patients with IEI have not controlled for race or social vulnerability. What does this article add to our knowledge ? For individuals with IEI, hospitalizations for SARS-CoV-2 were associated with race, ethnicity, obesity, and neurologic disease. Specific types of immunodeficiency, organ dysfunction, and social vulnerability were not associated with increased risk of hospitalization. How does this study impact current management guidelines? Current guidelines for the management of IEIs focus on risk conferred by genetic and cellular mechanisms. This study highlights the importance of considering variables linked with social determinants of health and common comorbidities as immunologic risk factors.


Prioritising Housing Maintenance to Improve Health in Indigenous Communities in NSW over 20 years.
Many studies document the relationship between housing quality and health status. Poor housing in Aboriginal communities continues to be linked to the compromised health status of Aboriginal Australians. The New South Wales (NSW) Housing for Health (HfH) program has been assessing and repairing Aboriginal community housing across the state for 20 years using a standardised intervention methodology that aims to improve the health of Aboriginal people in NSW by improving their living environments. Items are tested and repairs are prioritised to maximise safety and health benefits and measured against 11 Critical Healthy Living Priorities (e.g., safety, facilities for washing people and clothes, removing waste and preparing food). Descriptive analysis of data collected pre- and post-intervention from 3670 houses was conducted to determine the effectiveness of the program. Analysis demonstrated statistically significant improvements in the ability of the houses to support safe and healthy living for all critical healthy living priorities post-interventions. Trend analysis demonstrated the magnitude of these improvements increased over 20 years. In 24 communities (n = 802 houses) where projects were repeated (5-17 years later), results indicate sustainability of improvements for 9 of 11 priorities. However, the overall condition of health-related hardware in Aboriginal community housing across NSW pre-intervention has not significantly changed during the program's 20 years. Results suggest a systematic lack of routine maintenance and quality control continues to be the overwhelming cause for this lack of improvement pre-intervention. Our evaluation of the HfH program demonstrated that fidelity to a standardised housing testing and repair methodology to improve residents' safety and health can have sustainable effects on housing infrastructure and associated health benefits, such as a 40% reduction in infectious disease hospital separations. Housing and health agencies should collaborate more closely on social housing programs and ensure programs are adequately resourced to address safety and health issues.


Shockwave processing of beef brisket in conjunction with sous vide cooking: Effects on protein structural characteristics and muscle microstructure.
We studied the effect of shockwave processing and subsequent sous vide cooking on meat proteins (molecular size and thermal stability) and muscle structures (molecular, micro- and ultrastructure). Beef briskets were subjected to shockwave (11 kJ/pulse) and were sous vide-cooked at 60 °C for 12 h. Shockwave processing alone decreased the enthalpy and thermal denaturation temperature of the connective tissue proteins (second peak in the DSC thermogram, p < 0.05) compared to the control raw samples, while the protein gel electrophoresis profile remained unaffected. It led to disorganisation of the sarcomere structure and also modified the protein secondary structure. More severe muscle fibre coagulation and denaturation were observed in the shockwave-treated cooked meat compared to the cooked control. The results show that shockwave processing, with and without sous vide cooking, promotes structural changes in meat, and thus may have the potential to improve the organoleptic quality of the tough meat cuts.


Direct percutaneous ethanol instillation for treatment of venous malformation in the face and neck.
Venous malformations of the face and neck involve multiple anatomical spaces and encase critical neuromuscular structures, making surgical treatment difficult; high recurrence rates and high morbidity are well documented. Various methods of treatment of uncertain value and risk of complications have been advocated. We present our experience in treating five patients with venous malformation in the face and neck by using direct percutaneous ethanol sclerotherapy. Four patients had large lesions (> or = 3 cm; one patient had two large lesions in the low eyelid), and the other had a mid-sized lesion (1.5-3 cm). Under general or local anaesthesia, one-third to one-quarter cavity volume of ethanol was injected percutaneously, directly into the malformation with under fluoroscopy [de Lorimier AA. Sclerotherapy for venous malformations. J Pediatr Surg 1995;30:188-93; Johnson PL, Eckard DA, Brecheisen MA, Girod DA, Tsue TT. Percutaneous ethanol sclerotherapy of venous malformations of the tongue. Am J Neuroradiol 2002;23:779-82; Pappas DC Jr, Persky MS, Berenstein A. Evaluation and treatment of head and neck venous vascular malformations. Ear Nose Throat J 1998;77:914-22; Lee CH, Chen SG. Direct percutaneous ethanol sclerotherapy for treatment of a recurrent venous malformation in the periorbital region. ANZ J Surg. 2004;74(12):1126-7.]. Four patients required two injections. All patients had remission and alleviation of their symptoms, with no major complications. Direct percutaneous injection of absolute ethanol provides a simple and reliable alternative treatment for venous malformation in the face and neck.


Analysis on biological importance of antiseptic drug, O-Benzyl hydroxylamine, by the application of spectroscopic and theoretical tools.
Biological importance of antiseptic drug; O-Benzyl hydroxylamine was explored using QSAR studies for ultimate usage for treating fungal infections. In this research work, the molecular spectroscopic tool and theoretical calculation method of analysis. The data acquired from both tools were evaluated and compared to validate structural and vibrational characteristics. Mulliken charge displacement around molecular site in order for exploring electronic properties to find out the cause of inducement of drug potential. The Lipinski rule of five was evaluated for the measurement of biological importance of the drug compound. The lipophilicity and topological surface area of the drug was monitored for determining biological process activity. The partial involvement of compositional bonds of the molecule was appraised for influential vibrational characteristics. The chemical environment for making chemical property was monitored from the uniform and asymmetrical chemical shift of core and allied carbons. The resultant oscillating potential orientation in the molecular site was identified and the residing zones were recognized to find out the origin of drug potential. The occurrence of CT complex process was studied and the CTC was found to be CC and C-N for generating drug activeness. The enhancement of hyper active polarization was measured in first and second order from which the charge level pulling on different entities were observed for ensuring the biological affinity of the compound. The enantiomer characteristics were thoroughly studied to measure the level of toxicity.


Diurnal and seasonal responses of stomatal conductance for cowpea plants subjected to different levels of environmental drought.
Previously we reported that leaf conductance of cowpea (Vigna unguiculata) decreased with small changes in soil water status without associated changes in leaf water status. In these studies a larger range of soil water deficits was imposed in a rain-free environment by prolonged soil drying, and by weekly irrigation with different amounts of water. With progressive soil water deficits, leaf conductance and xylem pressure potential both declined, but in a manner which indicated that they were not related. Diurnal courses of leaf conductance usually indicated that stomatal opening occurred in the morning, and partial or complete stomatal closure occurred during midday and afternoon. This stomatal closure was associated with increases in air vapor pressure deficit. Day-to-day increases in leaf conductance, at times when radiation was not limiting stomatal opening, were associated with decreases in air vapor pressure deficits. However, maximum leaf conductances and their responses to vapor pressure deficit were generally smaller for plants subjected to greater depletion of soil water.


Longitudinal change detection in diffusion MRI using multivariate statistical testing on tensors.
This paper presents a longitudinal change detection framework for detecting relevant modifications in diffusion MRI, with application to neuromyelitis optica (NMO) and multiple sclerosis (MS). The core problem is to identify image regions that are significantly different between two scans. The proposed method is based on multivariate statistical testing which was initially introduced for tensor population comparison. We use this method in the context of longitudinal change detection by considering several strategies to build sets of tensors characterizing the variability of each voxel. These strategies make use of the variability existing in the diffusion weighted images (thanks to a bootstrap procedure), or in the spatial neighborhood of the considered voxel, or a combination of both. Results on synthetic evolutions and on real data are presented. Interestingly, experiments on NMO patients highlight the ability of the proposed approach to detect changes in the normal-appearing white matter (according to conventional MRI) that are related with physical status outcome. Experiments on MS patients highlight the ability of the proposed approach to detect changes in evolving and non-evolving lesions (according to conventional MRI). These findings might open promising prospects for the follow-up of NMO and MS pathologies.


Everyday discrimination as a predictor of maladaptive and adaptive eating: Findings from EAT 2018.
Various types of stressors are associated with maladaptive eating, but how the stressor of everyday discrimination (e.g., less respect, poorer service) relates to maladaptive eating and adaptive eating remains unclear. We examined everyday discrimination as a predictor of maladaptive and adaptive eating. Data were collected in a population-based study, Eating and Activity over Time (N = 1410, ages 18-30). Everyday discrimination was categorized as none, low, moderate, or high. Outcomes included maladaptive eating (i.e., overeating and binge eating) and adaptive eating (i.e., intuitive eating and mindful eating). Modified Poisson regressions estimated the prevalence ratios (PRs) for overeating and binge eating associated with everyday discrimination. Linear regressions estimated associations between everyday discrimination and intuitive and mindful eating scores. After adjustment for age, ethnicity/race, gender, and socioeconomic status, moderate and high levels of discriminatory experiences were each associated with a significantly greater prevalence of binge eating (PR = 2.2, [95% CI = 1.3-3.7] and PR = 3.1, [95% CI = 2.0-4.7], respectively) and lower intuitive (β = -0.4, [95% CI = -0.7, -0.2] and β = -0.5 [95% CI = -0.8, -0.3], respectively), and mindful eating scores (β = -0.3, [95% CI = -0.6, -0.1] and β = -0.5 [95% CI = -0.8, -0.3], respectively) compared to young adults with no discriminatory experience. Public health efforts to prevent maladaptive eating and encourage the adoption of adaptive eating should consider the potential contribution of everyday discrimination and the need to advocate for equity and inclusion.


A quicker simpler method of pre-determination of the length of umbilical artery catheter insertion in Asian babies.
A total of 50 neonates with birth weights varying from 919 gm to 5 kg with acute respiratory distress were studied for umbilical artery catheter placement in the thoracic aorta at T7 to T11 vertebral body level. The length of the catheter to be inserted was by a simple formula ie. for a 1000 gm baby, the length of insertion is 10 cm (delete the 00 from 1000 gm), and add 1 cm for each additional weight group of 250 gm till 2250 gm. Above 2250 gm, the length of insertion is 15 cm for all babies. Considering the 49 babies whose birth weights were more than a kg, 47 babies had catheter tips located at T7 and T11 vertebral body level. This method was thus accurate in 95.9% of babies studied.


Mating group size and evolutionarily stable pattern of sexuality in barnacles.
Barnacles, marine crustaceans, have various patterns of sexuality depending on species including simultaneous hermaphroditism, androdioecy (hermaphrodites and dwarf males), and dioecy (females and dwarf males). We develop a model that predicts the pattern of sexuality in barnacles by two key environmental factors: (i) food availability and (ii) the fraction of larvae that settle on the sea floor. Populations in the model consist of small individuals and large ones. We calculate the optimal resource allocation toward male function, female function and growth for small and large barnacles that maximizes each barnacle's lifetime reproductive success using dynamic programming. The pattern of sexuality is defined by the combination of the optimal resource allocations. In our model, the mating group size is a dependent variable and we found that sexuality pattern changes with the food availability through the mating group size: simultaneous hermaphroditism appears in food-rich environments, where the mating group size is large, protandric simultaneous hermaphroditism appears in intermediate food environments, where the mating group size also takes intermediate value, the other sexuality patterns, androdioecy, dioecy, and sex change are observed in food-poor environments, where the mating group size is small. Our model is the first one where small males can control their growth to large individuals, and hence has ability to explain a rich spectrum of sexual patterns found in barnacles.


Enhanced microbial lipid production by Cryptococcus albidus in the high-cell-density continuous cultivation with membrane cell recycling and two-stage nutrient limitation.
As a potential feedstock for biofuel production, a high-cell-density continuous culture for the lipid production by Cryptococcus albidus was investigated in this study. The influences of dilution rates in the single-stage continuous cultures were explored first. To reach a high-cell-density culture, a single-stage continuous culture coupled with a membrane cell recycling system was carried out at a constant dilution rate of 0.36/h with varied bleeding ratios. The maximum lipid productivity of 0.69 g/L/h was achieved with the highest bleeding ratio of 0.4. To reach a better lipid yield and content, a two-stage continuous cultivation was performed by adjusting the C/N ratio in two different stages. Finally, a lipid yield of 0.32 g/g and lipid content of 56.4% were obtained. This two-stage continuous cultivation, which provided a higher lipid production performance, shows a great potential for an industrial-scale biotechnological production of microbial lipids and biofuel production.


The role of cigarette smoking on new-onset of chronic kidney disease in a Japanese population without prior chronic kidney disease: Iki epidemiological study of atherosclerosis and chronic kidney disease (ISSA-CKD).
Studies regarding harmful effects of smoking on the new-onset of chronic kidney disease (CKD) have been limited. Thus, we collected and retrospectively studied 8 years of data from the annual health check-ups of the residents in Iki City (Nagasaki Prefecture, Japan). From 2008 to 2016, 4540 adults were enrolled in the study. Information on smoking habits was obtained via a self-reported questionnaire. New-onset CKD was defined as a reduction of the estimated globular filtration rate (eGFR) to less than 60 mL/min/1.73 m2 and/or new-onset proteinuria during the follow-up examinations. During an average follow-up of 4.6 years, proteinuria developed in 218 people (10.4 per 1000 person-years) and eGFR decline to less than 60 mL/min/1.73 m2 was confirmed in 594 people (28.3 per 1000 person-years) including 53 who showed both proteinuria and eGFR reduction (2.8 per 1000 person-years). In terms of proteinuria, current smokers showed a higher incidence than non-smokers (14.1 and 9.17 per 1000 person-years, respectively, p = 0.001), and a significantly high hazard ratio (HR) of 1.39 with a 95% CI of 1.01-1.92 in multivariable Cox's proportional-hazard analyses. The tendency was more drastic among younger participants (p = 0.015 for trend): current smokers who were < 50 years old had a significantly higher HR of 2.55 with a 95% CI of 1.01-6.45 (p = 0.004) than non-smokers. Smoking significantly increased the risk for new-onset of CKD based on proteinuria development in a Japanese population without CKD, and the association was more predominant in the younger population.


Acute intrahepatic biliary obstruction caused by hydatid cysts. Correlation between various imaging techniques.
An 18-year-old male was evaluated for recurrent attacks of right abdominal pain and intermittent jaundice caused by hydatid cysts of the liver. The case illustrates the value of dynamic functional information provided by Tc-99m-HIDA imaging over noninvasive modalities that demonstrate structural changes, such as ultrasound, computed tomography, and tin colloid liver imaging.


The immune checkpoint CD96 defines a distinct lymphocyte phenotype and is highly expressed on tumor-infiltrating T cells.
CD96 has recently been shown to be a potent immune checkpoint molecule in mice, but a similar role in humans is not known. In this study, we provide a detailed map of CD96 expression across human lymphocyte lineages, the kinetics of CD96 regulation on T-cell activation and co-expression with other conventional and emerging immune checkpoint molecules. We show that CD96 is predominantly expressed by T cells and has a unique lymphocyte expression profile. CD96high T cells exhibited distinct effector functions on activation. Of note, CD96 expression was highly correlated with T-cell markers in primary and metastatic human tumors and was elevated on antigen-experienced T cells and tumor-infiltrating lymphocytes. Collectively, these data demonstrate that CD96 may be a promising immune checkpoint to enhance T-cell function against human cancer and infectious disease.


[Enzymic determination of acetoacetate and D(--)-3-hydroxybutyrate in urine (author's transl)].
The enzymic methods for the quantitative determination of acetoacetate and D(--)-3-hydroxybutyrate in blood were modified for the routine determination of these compounds in urine for clinical purposes. Preliminary normal values are reported for children.


Flow cytometric studies of the D antigen of various Rh phenotypes with particular reference to Du and Del.
Flow cytometric analysis was performed on red cells (RBCs) to compare the antigen activity of various Rh phenotypes, including the rare variants Del and Du (both high-grade and low-grade), whose genotypes were confirmed or presumed by the family study. This appears to be the first report that the Del phenotype is due to the inhibitory effect of Cde. This study also compares the quantity of the D antigen in different phenotypes, whose genotypes comprise the same Du gene (cDuE) transmitted in a family. RBCs were stained by the indirect immunofluorescence method using IgG anti-D purified through a protein-A affinity column. The mean fluorescence intensity obtained for each genotype representing the activity of the D antigen decreased in the following order (percentages show relative fluorescence intensity taking cDE/cDE control as 100% and Cde/cde as 0%): CDe/cDE, 76 percent; CDe/cde, 73 percent; cDE/Cde, 70 percent; cDE/cDuE, 68 percent; CDe/Cde (high-grade Du), 59 percent; cDuE/cde (low-grade Du), 6 percent; and cDuE/Cde (Del), 3 to 4 percent.


A(2A)/D(2) receptor heteromerization in a model of Parkinson's disease. Focus on striatal aminoacidergic signaling.
The present manuscript mainly summarizes the basic concepts and the molecular mechanisms underlying adenosine A(2A)-dopamine D(2) receptor-receptor interactions in the basal ganglia. Special emphasis is placed on neurochemical, behavioral and electrophysiological findings supporting the functional role that A(2A)/D(2) heteromeric receptor complexes located on striato-pallidal GABA neurons and corticostriatal glutamate terminals play in the regulation of the so called "basal ganglia indirect pathway". Furthermore, the role of A(2A)/mGluR(5) synergistic interactions in striatal neuron function and dysfunction is discussed. The functional consequences of the interactions between striatal adenosine A(2A), mGluR(5) and dopamine D(2) receptors on striatopallidal GABA release and motor behavior dysfunctions suggest the possibility of simultaneously targeting these receptors in Parkinson's disease treatment. This article is part of a Special Issue entitled Brain Integration. This article is part of a Special Issue entitled: Brain Integration.