Modelling during an emergency: the 2009 H1N1 influenza pandemic.
During the 2009 H1N1 pandemic, decision-makers had access to mathematical and computational models that were not available in previous pandemics in 1918, 1957, and 1968. How did models contribute to policy and action during the 2009 H1N1 pandemic? Modelling encountered six primary challenges: (i) expectations of modelling were not clearly defined; (ii) appropriate real-time data were not readily available; (iii) modelling results were not generated, shared, or disseminated in time; (iv) decision-makers could not always decipher the structure and assumptions of the models; (v) modelling studies varied in intervention representations and reported results; and (vi) modelling studies did not always present the results or outcomes that are useful to decision-makers. However, there were also seven general successes: (i) modelling characterized the role of social distancing measures such as school closure; (ii) modelling helped to guide data collection; (iii) modelling helped to justify the value of the vaccination programme; (iv) modelling helped to prioritize target populations for vaccination; (v) modelling addressed the use of antiviral medications; (vi) modelling helped with health system preparedness planning; and (vii) modellers and decision-makers gained a better understanding of how to work with each other. In many ways, the 2009 pandemic served as practice and a learning opportunity for both modellers and decision-makers. Modellers can continue working with decision-makers and other stakeholders to help overcome these challenges, to be better prepared when the next emergency inevitably arrives.


Effective salt criteria in callus-cultured tomato genotypes.
Na+, Cl-, K+, Ca2+, and proline contents, the rate of lipid peroxidation level in terms of malondialdehyde (MDA) and chlorophyll content, and the changes in the activity of antioxidant enzymes, such as superoxide dismutase (SOD: EC 22.214.171.124), catalase (CAT: EC 188.8.131.52), ascorbate peroxidase (APX: EC 22.214.171.124), and glutathione reductase (GR: EC 22.214.171.124), in tissues of five tomato cultivars in salt tolerance were investigated in a callus culture. The selection of effective parameters used in these tomato genotypes and to find out the use of in vitro tests in place of in vivo salt tolerance tests were investigated. As a material, five different tomato genotypes during a 10-day time period were used, and 150 mM NaCl was applied at callus plant tissue. The exposure to NaCl induced a significant increase in MDA content in both salt-resistant and salt-sensitive cultivars. But the MDA content was higher in salt-sensitive cultivars. The chlorophyll content was more decreased in salt-sensitive than in salt-resistant ones. The proline amount was more increased in salt-sensitive than in salt-resistant ones. It has been reported that salt-tolerant plants, besides being able to regulate the ion and water movements, also exhibit a strong antioxidative enzyme system for effective removal of ROS. The degree of damage depends on the balance between the formation of ROS and its removal by the antioxidative scavenging system that protects against them. Exclusion or inclusion of Na+, Cl-, K+, and Ca2+, antioxidant enzymes and MDA concentration play a key protective role against stress, and this feature at the callus plant tissue used as an identifier for tolerance to salt proved to be an effective criterion.


A practical measure of impairment: psychometric properties of the impairment rating scale in samples of children with attention deficit hyperactivity disorder and two school-based samples.
Assessing impairment is an explicit component of current psychiatric diagnostic systems. A brief parent and teacher rating scale for assessing impairment was developed and studied using attention deficit hyperactivity disorder (ADHD) as an exemplar disorder. The psychometric properties of the Impairment Rating Scale (IRS) were measured in 4 samples. Two included ADHD and matched comparison children and the other 2 a school sample. Overall, IRS ratings exhibited very good temporal stability. They correlated with other impairment ratings and behavioral measures and displayed evidence of convergent and discriminant validity. The IRS was highly effective in discriminating between children with and without ADHD. Evidence that the parent and teacher IRS accounted for unique variance beyond ratings of ADHD symptoms is also presented. The scale is brief, practical, and in the public domain. The results of the studies and implications for the assessment of impairment are discussed.


Up-regulation of the endocannabinoid system in the uterus of leptin knockout (ob/ob) mice and implications for fertility.
The levels of the endocannabinoids anandamide and 2-arachidonoylglycerol (2-AG) are under the negative control of leptin in the rodent hypothalamus. As leptin and endocannabinoids play opposite roles in the control of reproduction, we have investigated whether the impaired fertility typical of leptin-defective ob/ob mice is due, in part, to enhanced uterine endocannabinoid levels. We found that levels of both anandamide and 2-AG in the uterus of ob/ob mice are significantly elevated with respect to wild-type littermates, due to reduced hydrolase activity in the case of anandamide, and to reduced monoacylglycerol lipase and enhanced diacylglycerol lipase activity in the case of 2-AG. Furthermore, the process mediating endocannabinoid cellular uptake was also impaired in ob/ob mice, whereas the levels of cannabinoid and anandamide receptors were not modified. Although ineffective in wild-type mice, treatment of ob/ob mice with leptin re-established endocannabinoid levels and enzyme activities back to the values observed in wild-type littermates. Finally, treatment of ob/ob females with the CB1 receptor antagonist SR141716A did not improve their fertility, and inhibition of endocannabinoid inactivation with the endocannabinoid uptake inhibitor OMDM-1 in wild-type females did not result in impaired fertility.


Excretion of glutathione by methylglyoxal-resistant Escherichia coli.
A methylglyoxal-resistant mutant of Escherichia coli B excreted glutathione into the growth medium, especially during growth on medium containing methylglyoxal. In the presence of methylglyoxal, the total amount of glutathione excreted was increased about 50-fold over that of the wild-type strain. The resistant mutant had high activities of two enzyme systems: a glutathione-forming enzyme system (consisting of gamma-glutamylcysteine synthetase and glutathione synthetase) and a glyoxalase system (consisting of glyoxalase I and glyoxalase II). Methylglyoxal resistance appeared to be due to the simultaneous increase in the activities of these two enzyme systems.


Determination of a dipeptidyl peptidase IV agonist, β-aminoacyl containing thiazolidine derivatives (KR-66223) in rat plasma by liquid chromatography-tandem mass spectrometry.
A sensitive liquid chromatography/tandem mass spectrometry (LC-MS/MS) method was developed for a novel dipeptidyl peptidase IV agonist (DDP-IV) agonist, KR-66223, in rat plasma. It involves liquid-liquid extraction (LLE) followed by HPLC separation and electrospray ionization tandem mass spectrometry. KR-66223 and imipramine (IS) was separated on Gemini-NX C18 column with mixture of acetonitrile-ammonium formate (10mM) (90:10, v/v) as mobile phase. The ion transitions monitored were m/z 553.2→206.2 for KR-66223, m/z 281.3→86.1 for imipramine in multiple reaction monitoring (MRM) mode. The linear ranges of the assay were 0.003-10μg/ml with a correlation coefficient (R(2)) greater than 0.99 and the lower limit of quantification was 3ng/ml. The average recovery was 78.9% and 87.1% from rat plasma for KR-66223 and imipramine, respectively. The coefficients of variation of intra- and inter-assay were 3.9-14.4% and the relative error was 0.8-11.5%. The method was validated and successfully applied to the pharmacokinetic study of KR-66223 in rat.


The incidence and modifiable risk factors for necrotizing enterocolitis in preterm infants: a retrospective cohort study.
To evaluate the incidence and modifiable risk factors for Necrotizing enterocolitis (NEC) in preterm infants born at ≤32 weeks of gestation weighing <1500 grams, at a private tertiary care hospital in Kenya. This retrospective cohort study was conducted at the Aga Khan University Hospital Neonatal Intensive Care Unit (NICU). Preterm infants born at ≤ 32 weeks' gestation and weighing <1500 grams admitted to NICU between 2009 and 2019, were recruited into the study. The primary outcome was NEC Bell Stage IIa-IIIb based on Modified Bell's criteria. Maternal and neonatal characteristics were evaluated. The association between variables of interest and NEC was determined using logistic regression analysis and the incidence of NEC for the study period was calculated. A total of 261 charts of infants born at ≤ 32 weeks' gestation, weighing <1500 were reviewed, and 200 charts met the inclusion criteria. Fifteen preterm infants developed the primary outcome of interest: NEC Stage ≥2a within the first 30 days of admission. The overall incidence of NEC for the study period was 7.5%. Three risk factors were identified as significantly associated with NEC on multivariate logistic regression analysis: antenatal exposure to steroids (OR = 0.056 CI = 0.003-0.964 p = 0.047), cumulative duration of exposure to invasive mechanical ventilation (OR = 2.172 CI = 1.242-3.799 p = 0.007) and cumulative duration of exposure to umbilical vein catheter (OR = 1.344 CI = 1.08-1.672 p = 0.008). The overall incidence for the study period of NEC Stage ≥ II a was 7.5%. Exposure to antenatal steroids, duration of mechanical ventilation, and duration of umbilical vein catheterization were three independent modifiable risk factors for NEC Stage II a-Stage III b.


[Effect of different fixation methods and partial chemical sympathetic denervation on cell size and 3H-leucine incorporation by rat sympathetic neurocytes].
Dimensions of sympathetic nerve cells and of their nuclei were studied using various methods of fixation and embedding media, as well as autoradiographic indices of the protein synthesized system of neurocytes in normal rats, and in rats partially sympathectomized at an early age. On the ground of different changes in the average size of neurocytes seen under various methods of fixation, and of decreased labeling intensity of large neurocytes after the injection of the labeled protein biosynthesis precursor there is some reason to believe that large neurocytes may appear in the late reproductive age mainly due to the nerve cell cytoplasm swelling as a consequence of exhaustion of their growth resources.


Potent mechanism-based sirtuin-2-selective inhibition by an in situ-generated occupant of the substrate-binding site, "selectivity pocket" and NAD+-binding site.
Sirtuin 2 (SIRT2), a member of the NAD+-dependent histone deacetylase family, has recently received increasing attention due to its potential involvement in neurodegenerative diseases and the progression of cancer. Potent and selective SIRT2 inhibitors thus represent desirable biological probes. Based on the X-ray crystal structure of SIRT2 in complex with a previously reported weak inhibitor (6), we identified in this study the potent mechanism-based inactivator KPM-2 (36), which is selective toward SIRT2. Compound 36 engages in a nucleophilic attack toward NAD+ at the active site of SIRT2, which affords a stable 36-ADP-ribose conjugate that simultaneously occupies the substrate-binding site, the "selectivity pocket" and the NAD+-binding site. Moreover, 36 exhibits antiproliferative activity in cancer cells and remarkable neurite outgrowth activity. This strategy for the selective inhibition of SIRT2 should allow further probing of the biology of SIRT2, and promote the development of new disease treatment strategies.


[Adaptation of energy metabolism of liver and muscles in the rabbit to hypobaric hypoxia].
The adaptation of rabbits to hypobaric hypoxia results in stable changes in energy metabolism. During posthypoxic recovery the levels of ATP and ATP+ADP in the liver are decreased, while the Pi content and the cytosolic NAD+/NADH ratio are increased; the steady state concentrations of glucose, pyruvate, lactate and adenine nucleotides and the rate of glycolysis are increased after hypoxic exposure. Succinate oxidation by liver mitochondria from hypoxia-adapted rabbits is accelerated as compared to normal animals; however, the coupling, rate and efficiency of oxidative phosphorylation remain unchanged. At enhanced gluconeogenesis all the parameters of phosphorylating succinate oxidation are impaired. Possible pathways of energy supply for gluconeogenesis are discussed.


Exploring Correlations of Food-Specific Disgust with Eating Disorder Psychopathology and Food Interaction: A Preliminary Study Using Virtual Reality.
The emotion of disgust is thought to play a critical role in maintaining restrictive eating among individuals with anorexia nervosa. This exploratory cross-sectional study examined correlations between food-specific trait and state disgust, eating disorder psychopathology, illness severity (body mass index: BMI), and interactions with virtual foods in people with anorexia nervosa. Food-specific trait disgust and eating disorder symptoms were measured before exposure to virtual foods in one of three virtual reality (VR) kitchens to which participants were randomly allocated. Food interactions (eye gaze and reaching towards virtual foods) were measured during the VR exposure. Food-specific state disgust ratings were collected after the VR exposure. In the entire sample, eating disorder symptoms correlated positively with food-specific trait disgust (rs (68) = 0.45, p < 0.001). We also found a significant association between food-specific state disgust and eating disorder symptoms in each virtual kitchen scenario: virtual kitchen only (rs (22) = 0.40, p = 0.05), virtual kitchen plus pet (rs (22) = 0.80, p < 0.001), and virtual kitchen plus avatar (rs (20) = 0.78, p < 0.001). No significant correlation was observed for the link between food-specific disgust measures and food-related touch. Correlations between food-specific trait disgust and food-related eye gaze differed across scenarios. The current experimental paradigm needs to be improved to draw firm conclusions. Both food-specific trait and state disgust are associated with eating disorder psychopathology, and therefore, effective strategies are warranted to attenuate food-specific disgust.


[Approaches to classifying bifidobacteria based on DNA structural data].
A brief historical review of classifications of Bifidobacteria demonstrates the difficulties in this problem, for the present-day classifications are far from being satisfactory. Based on the genotypical heterogeneity of the genus Bifidobacterium, the authors validate the possibility of raising it to the status of the family Bidobacteriaceae fam. nov. The principle of forming new genera within the frames of this hypothetical family, discussed in the paper, originates from the genomic similarity of representatives of some species of this group of microorganisms.


Prolonged direct catheter thrombolysis of cerebral venous sinus thrombosis in children: a case series.
Cerebral venous sinus thrombosis is a rare condition with potentially devastating neurologic outcome--death and severe disability are common in advanced cases. In adults, protocols for mechanical clot disruption and direct thrombolysis are established; no guidance exists for children. We present our experience of 6 children with cerebral venous sinus thrombosis and ominous clinical progression. We found that effective thrombolysis required substantially longer infusion, more rounds of mechanical disruption, and higher doses of thrombolytics than are commonly practiced. Despite pervasive thrombosis, prethrombolysis hemorrhage, coma, and other predictors of death and disability, our patients survived and 4 of 6 had no functional deficits. One patient had moderate, and one had severe deficits. We report these cases to illustrate that hemorrhage may not be a contraindication to thrombolysis for cerebral venous sinus thrombosis, that prolonged infusion may be required to restore perfusion, and that good neurologic outcomes can be achieved despite dire clinical presentations and extensive sinus thrombosis.


IL28B polymorphism genotyping as predictor of rapid virologic response during interferon plus ribavirin treatment in hepatitis C virus genotype 1 patients.
To clarify the association of interleukin-28B (IL28B) single nucleotide polymorphisms (SNPs) with hepatitis C virus (HCV) viremia changes for assessment of interferon (IFN) response. A cohort of 118 Caucasian treatment-naïve HCV-G1 infected patients, treated with pegylated-IFN alpha 2a or 2b associated with ribavirin (53 responders, 65 non-responders) during the period 2010-2012, were genotyped for IL28B SNPs rs12979860 C>T and rs8099917 T>G. Genotyping was performed by real-time allelic discrimination assay. Serum HCV RNA levels were assayed at 2, 4, 12, 24 and 48 wk during therapy. Correlation between IL28B genotypes and serum HCV RNA kinetics was investigated. Multivariable logistic regression analysis was performed to identify predictors of null-response. Twenty-six out of 118 patients (22%) had no HCV RNA decline ≥ 1 log IU/mL at therapy week 4 (null-responders). IL28B genotype was rs8099917 (G)/rs1297860 in 21/26 (80%) of null-responder patients. Using multivariate analysis, it was shown that the presence of the rs8099917 G allele was the best predictor of null-response (OR = 7.9, 95%CI: 1.99-31.18). The presence of at least one favorable genotype showed a positive predictive value of above 90% for HCV RNA reduction ≥ log at week 4. Analysis of the HCV RNA kinetics during 12 wk of therapy in patients with IL28B rs12979860 CT heterozygosis (n = 73), according to their rs8099917 status, showed that the viremia reduction was significantly different in patients carrying the rs8099917 G allele compared to those with favorable homozygosis. Our findings emphasize the association of the IL28B rs8099917 G allele with HCV. Genotyping for both IL28B SNPs is useful in clinical practice for thorough patient risk stratification based on IFN responsiveness.


Adenovirus infection in allogeneic hematopoietic cell transplantation.
Adenovirus (AdV) infection occurs in 0-20% of patients in the first 3-4 months after allogeneic hematopoietic cell transplantation (HCT), being higher in pediatric than in adult patients. About 50% of AdV infections involve the blood, which in turn, correlates with an increased risk developing AdV diseases, end-organ damage, and 6-month overall mortality. The main risk factors for AdV infection are T-cell depletion of the graft by ex vivo selection procedures or in vivo use of alemtuzumab or antithymocyte serum, development of graft versus host disease (GVHD) grade III-IV, donor type (haploidentical or human leucocyte antigen mismatched related donor > cord blood> unrelated matched donor) and severe lymphopenia (<0.2 × 109 /L). The prevention of AdV disease relies on early diagnosis of increasing viral replication in blood or stool and the pre-emptive start of cidofovir as viral load exceeds the threshold of ≥102-3 copies/mL in blood and/or 106 copies/g stool in the stool. Cidofovir (CDV), a cytosine monophosphate nucleotide analog, is currently the only antiviral recommended for AdV infection despite limited efficacy and moderate risk of nephrotoxicity. Brincidofovir, a lipid derivative of CDV with more favorable pharmacokinetics properties and superior efficacy, is not available and currently is being investigated for other viral infections. The enhancement of virus-specific T-cell immunity in the first few months post-HCT by the administration of donor-derived or third-party-donor-derived virus-specific T-cells represents an innovative and promising modality of intervention and data of efficacy and safety of the ongoing prospective randomized studies are eagerly awaited.


Stereomorphology of the glandular parenchyma of the inferoposterolateral area of human prostate gland.
Introduction: The human prostate gland contains numerous tubular masses of different calibers in its parenchyma. They form the tubuloalveolar prostate glandules, constituting from numerous prostatic excretory ductules as well as major excretory ducts. The aim: The study was aimed at 3D visualization of individual microelements of the tubuloalveolar aggregations, localized within the peripheral area. Materials and methods: To meet the objectives of the study a series of paraffin plane-parallel 4 μm sections has been obtained in the peripheral prostate area. The serial sections were stained with hematoxylin and eosin. After the analysis of the series of sections, the graphical two-dimensional and plastic 3D reconstructions of the investigated microobjects have been made sequentially in depth. Results: Presence of the epithelial creases and invaginations of the wall in the luminal contour of tubuloalveolar aggregations of the prostate has been found. Creases can be solitary, multiple, or wavy; they can be localized both symmetrically and asymmetrically, with different heights and thicknesses. Intraluminal invaginations, along with the epithelial crease, contain a stromal muscle component with localized blood loop-shaped microvessel. The creases of the glandular epithelium and intraluminal invaginations can "overlap" the lumens of the tubuloalveolar aggregations up to 2/3 of the width, making the inner lumen sinuous that influences the laminar flow of the liquid. Conclusions: Alternation of the considerable enlargement and narrowing of the inner diameter is common for the tubuloalveolar aggregations which can affect the secreta deposition and movement.


Biomarkers for Salvage Therapy in Testicular Germ Cell Tumors.
The outcome of metastatic testicular germ cell tumor patients has been dramatically improved by cisplatin-based chemotherapy combinations. However, up to 30% of patients with advanced disease relapse after first-line therapy and require salvage regimens, which include treatments with conventional-dose chemotherapy or high-dose chemotherapy with autologous stem cell transplantation. For these patients, prognosis estimation represents an essential step in the choice of medical treatment but still remains a complex challenge. The available histological, clinical, and biochemical parameters attempt to define the prognosis, but they do not reflect the tumor's molecular and pathological features and do not predict who will exhibit resistance to the several treatments. Molecular selection of patients and validated biomarkers are highly needed in order to improve current risk stratification and identify novel therapeutic approaches for patients with recurrent disease. Biomolecular biomarkers, including microRNAs, gene expression profiles, and immune-related biomarkers are currently under investigation in testicular germ cell tumors and could potentially hold a prominent place in the future treatment selection and prognostication of these tumors. The aim of this review is to summarize current scientific data regarding prognostic and predictive biomarkers for salvage therapy in testicular germ cell tumors.


Cigarette smoking and depression comorbidity: systematic review and proposed theoretical model.
Despite decades of research on co-occurring smoking and depression, cessation rates remain consistently lower for depressed smokers than for smokers in the general population, highlighting the need for theory-driven models of smoking and depression. This paper provides a systematic review with a particular focus upon psychological states that disproportionately motivate smoking in depression, and frame an incentive learning theory account of smoking-depression co-occurrence. We searched PubMed, Scopus, PsychINFO and CINAHL to December 2014, which yielded 852 papers. Using pre-established eligibility criteria, we identified papers focused on clinical issues and motivational mechanisms underlying smoking in established, adult smokers (i.e. maintenance, quit attempts and cessation/relapse) with elevated symptoms of depression. Two reviewers determined independently whether papers met review criteria. We included 297 papers in qualitative synthesis. Our review identified three primary mechanisms that underlie persistent smoking among depressed smokers: low positive affect, high negative affect and cognitive impairment. We propose a novel application of incentive learning theory which posits that depressed smokers experience greater increases in the expected value of smoking in the face of these three motivational states, which promotes goal-directed choice of smoking behavior over alternative actions. The incentive learning theory accounts for current evidence on how depression primes smoking behavior and provides a unique framework for conceptualizing psychological mechanisms of smoking maintenance among depressed smokers. Treatment should focus upon correcting adverse internal states and beliefs about the high value of smoking in those states to improve cessation outcomes for depressed smokers.


Pesticide residues in food: investigation of disparities in cancer risk estimates.
Much of the public perceives that exposure to synthetic pesticide residues in the diet is a major cause of cancer. The National Research Council (NRC), in a 1987 report, Regulating Pesticides in Food: The Delaney Paradox, evaluated cancer risks for 29 pesticides that are rodent carcinogens and estimated that the risks for 23 were greater than one-in-a-million. In contrast, our group has ranked possible carcinogenic hazards from a variety of human exposures to rodent carcinogens using the HERP (Human Exposure/Rodent Potency) index, and found that dietary residues of synthetic pesticides ranked low. This paper evaluates the disparities in these analyses by examining the two components of risk assessment: carcinogenic potency in rodents and human exposure. Potency estimates based on rodent bioassay data are shown to be similar whether calculated, as in the NRC report, as the regulatory q1* or as TD50. In contrast, estimates of dietary exposure to residues of synthetic pesticides vary enormously, depending on whether they are based on the Theoretical Maximum Residue Contribution (TMRC) calculated by the Environmental Protection Agency vs. the average dietary residues measured by the Food and Drug Administration in the Total Diet Study (TDS). The TMRC is the theoretical maximum human exposure anticipated under the most severe field application conditions, which are far greater than dietary residues measured in the TDS. Several independent exposure studies suggest that the FDA dietary residues are reasonable estimates of average human exposures, whereas TMRC values are large overestimates. Using standard methodology and measured dietary residues in the TDS, the estimate of excess cancer risk from average lifetime exposure to synthetic pesticide residues in the diet appears to be less than one-in-a-million for each of the ten pesticides for which adequate data were available.


Synchrony and specificity in the maternal and the paternal brain: relations to oxytocin and vasopressin.
Research on the neurobiology of parenting has defined biobehavioral synchrony, the coordination of biological and behavioral responses between parent and child, as a central process underpinning mammalian bond formation. Bi-parental rearing, typically observed in monogamous species, is similarly thought to draw on mechanisms of mother-father synchrony. We examined synchrony in mothers' and fathers' brain response to ecologically valid infant cues. Thirty mothers and fathers, comprising 15 couples parenting 4- to 6-month-old infants, were visited at home, and infant play was videotaped. Parents then underwent functional magnetic resonance imaging scanning while observing own-infant compared with standard-infant videos. Coordination in brain response between mothers and fathers was assessed using a voxel-by-voxel algorithm, and gender-specific activations were also tested. Plasma oxytocin and arginine vasopressin, neuropeptides implicated in female and male bonding, were examined as correlates. Online coordination in maternal and paternal brain activations emerged in social-cognitive networks implicated in empathy and social cognition. Mothers showed higher amygdala activations and correlations between amygdala response and oxytocin. Fathers showed greater activations in social-cognitive circuits, which correlated with vasopressin. Parents coordinate online activity in social-cognitive networks that support intuitive understanding of infant signals and planning of adequate caregiving, whereas motivational-limbic activations may be gender specific. Although preliminary, these findings demonstrate synchrony in the brain response of two individuals within an attachment relationship, and may suggest that human attachment develops within the matrix of biological attunement and brain-to-brain synchrony between attachment partners.


AIDS-related Burkitt lymphoma in the United States: what do age and CD4 lymphocyte patterns tell us about etiology and/or biology?
Trimodal or bimodal age-specific incidence rates for Burkitt lymphoma (BL) were observed in the United States general population, but the role of immunosuppression could not be excluded. Incidence rates, rate ratios, and 95% confidence intervals for BL and other non-Hodgkin lymphoma (NHL), by age and CD4 lymphocyte count categories, were estimated using Poisson regression models using data from the United States HIV/AIDS Cancer Match study (1980-2005). BL incidence was 22 cases per 100 000 person-years and 586 for non-BL NHL. Adjusted BL incidence rate ratio among males was 1.6× that among females and among non-Hispanic blacks, 0.4× that among non-Hispanic whites, but unrelated to HIV-transmission category. Non-BL NHL incidence increased from childhood to adulthood; in contrast, 2 age-specific incidence peaks during the pediatric and adult/geriatric years were observed for BL. Non-BL NHL incidence rose steadily with decreasing CD4 lymphocyte counts; in contrast, BL incidence was lowest among people with ≤ 50 CD4 lymphocytes/μL versus those with ≥ 250 CD4 lymphocytes/μL (incidence rate ratio 0.3 [95% confidence interval = 0.2-0.6]). The bimodal peaks for BL, in contrast to non-BL NHL, suggest effects of noncumulative risk factors at different ages. Underascertainment or biological reasons may account for BL deficit at low CD4 lymphocyte counts.


Pathway-specific inputs to the superior colliculus support flexible responses to visual threat.
Behavioral flexibility requires directing feedforward sensory information to appropriate targets. In the superior colliculus, divergent outputs orchestrate different responses to visual threats, but the circuit organization enabling the flexible routing of sensory information remains unknown. To determine this structure, we focused on inhibitory projection (Gad2) neurons. Trans-synaptic tracing and neuronal recordings revealed that Gad2 neurons projecting to the lateral geniculate nucleus (LGN) and the parabigeminal nucleus (PBG) form two separate populations, each receiving a different set of non-retinal inputs. Inhibiting the LGN- or PBG-projecting Gad2 neurons resulted in opposing effects on behavior; increasing freezing or escape probability to visual looming, respectively. Optogenetic activation of selected inputs to the LGN- and PBG-projecting Gad2 cells predictably regulated responses to visual threat. These data suggest that projection-specific sampling of brain-wide inputs provides a circuit design principle that enables visual inputs to be selectively routed to produce context-specific behavior.


Efficacy of Pt-modified TiO(2) nanoparticles in cardiac cells.
The application of TiO(2) nanoparticles promises to revolutionize cardiac imaging and targeted medical treatment. A novel type of platinum-modified TiO(2) (Pt-TiO(2)) nanoparticle was synthesized and characterized. Commercially available P25 TiO(2) nanoparticles were used for comparison. Cellular toxicity and its mechanisms were evaluated by analyzing nanoparticle uptake, oxidative stress and mitochondrial membrane potential in rat cardiac (H9c2) cells. There was greater cellular uptake of Pt-TiO(2). Furthermore, Pt-TiO(2) caused a greater increase in oxidative stress and greater decrease in mitochondrial membrane potential. These data suggest that Pt modification of TiO(2) nanoparticles rendered them more cytotoxic than their commercial counterparts at lower, more physiologically relevant concentrations. Despite the functional advantages of Pt modification, which results in increased uptake at a lower concentration, the corresponding increase in cardiotoxic effect indicates that a thoughtful, cautious approach to cardiac nanotechnologies is required.


Including riparian vegetation in the definition of morphologic reference conditions for large rivers: a case study for Europe's Western Plains.
Methods for defining and retrieving reference conditions for large rivers were explored with emphasis on hydromorphologic and biologic quality indicators. For a set of four large rivers in the European Western Plains ecoregion, i.e., the rivers Meuse, Loire, Allier, and Dordogne, reference reaches were selected based on geomorphologic characteristics. A survey of riparian land use, vegetation, and bed geometry was done for the selected reaches. Responses of the riparian landscape to hydromorphologic conditions were determined with a set of existing and newly developed measures of riparian dynamics and forest development. Strong correlations were observed at the reach and local levels between the ratios of width to depth and embankment and the developed measures of riparian dynamics and forest. Boundary conditions for riparian forest development were determined for the hydromorphologic and biologic indicators of riparian dynamics and vegetation structure. These conditions also proved useful for determining the presence of sustainable populations of Populus nigra and Salix purpurea. From this agreement between abiotic and biotic boundary conditions, a set of useful reference conditions was determined, and a framework for the definition of reference and good status conditions subsequently evolved. Finally, a proposal for assessment and monitoring the proposed indicators is discussed for its applicability.


The production of human parvovirus capsid proteins in Escherichia coli and their potential as diagnostic antigens.
We have expressed a number of polypeptides derived from the capsid proteins of the human parvovirus B19 in Escherichia coli. These include native VP1 (84K) and VP2 (58K) proteins and also fusions to beta-galactosidase containing differing amounts of the amino terminus of the VP1/2 polypeptide. Although each of these was expressed at high levels and the majority were produced as full-length proteins, only one was soluble. This soluble polypeptide, p132, is a beta-galactosidase fusion protein that includes 145 amino acids from B19 which are entirely derived from the region unique to VP1. Despite containing such a small portion of VP1, which itself constitutes only 4% of total capsid protein, p132 reacted with all our known anti-B19 IgM-positive human serum samples. We conclude that this region contains epitopes which must be prominently exposed on the intact virus. We have demonstrated the use of this recombinant antigen in a simple diagnostic assay for B19-specific antibodies which can be used for initial screening of human serum samples. In a survey of 103 serum specimens, our ELISA positively identified all samples (19/19) which were positive by IgM antibody capture radioimmunoassay. The recombinant p132 antigen is efficiently produced and readily purified from E. coli, and its use as a diagnostic antigen should increase the availability of routine clinical testing for human parvovirus infection.


Composition of healthy diets for older persons.
This study aims to review recent evidence (2022-2023) on the role of diet in promoting healthy aging in older adults. Current evidence of diet and healthy aging is limited to epidemiological studies. A healthy diet is beneficial for individual domains of intrinsic capacity, that is, cognition, locomotion, vitality, psychological, and/or sensory functions, with sex-specific differences reported. Only a few studies used the multidimensional concept of intrinsic capacity as an outcome. This review supports that a healthy diet for older adults consists of plenty of plant-based foods, adequate protein-rich foods, and healthy fats. Next to quantity, improving the quality and variety within food groups play a role in optimizing health. Data on the associations between adherence to national food-based dietary guidelines and intrinsic capacity are scarce. A healthy diet, centered on plant-based foods, adequate protein-rich foods and healthy fats, potentially promotes healthy aging. Future studies may evaluate the association between adherence to healthy dietary patterns (particularly national food-based dietary guidelines) and the multidimensional concept of intrinsic capacity, with consideration of sex-specific differences. Clinical trials are warranted to inform the causal effects of diet and outcomes related to intrinsic capacity.


Embracing high performance potassium-ion batteries with phosphorus-based electrodes: a review.
The ever-increasing global energy demand and rising price of raw materials adopted in currently prevalent lithium ion batteries (LIBs) have boosted the development of potassium ion batteries (KIBs). Despite the similarity in the working principle to LIBs, it remains a big challenge to select a suitable electrode material for KIBs. Phosphorus (P) and P-based composites have been identified as promising electrodes for LIBs or sodium ion batteries (NIBs) with remarkable electrochemical performance. Yet it was not until recent years that P-based materials have been explored as potential electrodes for KIBs. In this paper, we will try to provide a timely review of the current research progress of the P-based electrode materials, both cathodes and anodes, for KIBs. The synthetic strategies, electrochemical behaviours, and ion storage mechanisms will be discussed in detail. The challenges and future perspectives worth investigating will also been presented. Through timely update of the research progress and presentation of the existing arguments, it is expected that this review will help to clarify the puzzles encountered in current KIBs and benefit their future development and commercialization.


Carotid endarterectomy under local and/or regional anesthesia has less risk of myocardial infarction compared to general anesthesia: An analysis of national surgical quality improvement program database.
Multiple studies have evaluated the effect of anesthesia type on carotid endarterectomy with inconsistent results. Our study compared 30-day postoperative myocardial infarction, stroke, and mortality between carotid endarterectomy under local or regional anesthesia and carotid endarterectomy under general anesthesia utilizing National Surgical Quality Improvement Program database. All patients listed in National Surgical Quality Improvement Program database that underwent carotid endarterectomy under general anesthesia and local or regional anesthesia from 2005 to 2011 were included with the exception of patients undergoing simultaneous carotid endarterectomy and coronary artery bypass grafting. The data revealed substantial differences between the two groups compared, and these were adjusted using multiple logistic regression. Postoperative myocardial infarction, stroke, and death at 30 days were compared between the two groups. A total of 42,265 carotid endarterectomy cases were included. A total of 37,502 (88.7%) were performed under general anesthesia and 4763 (11.3%) under local or regional anesthesia. Carotid endarterectomy under local or regional anesthesia had a significantly decreased risk of 30-day postoperative myocardial infarction when compared to carotid endarterectomy under general anesthesia (0.4% vs 0.86%, p = 0.012). No statistically significant differences were found in postoperative stroke or mortality. Carotid endarterectomy under local or regional anesthesia carries a decreased risk of postoperative myocardial infarction when compared to carotid endarterectomy under general anesthesia. Therefore, patients at risk of postoperative myocardial infarction undergoing carotid endarterectomy, consideration of local or regional anesthesia may reduce that risk.


Schizophrenia and offspring's risk for adverse pregnancy outcomes and infant death.
Women with schizophrenia are at increased risk for adverse pregnancy outcomes. It is not known whether offspring born to fathers with schizophrenia also have an increased risk. To evaluate paternal and maternal influences on the association between schizophrenia and pregnancy outcomes. A record linkage including 2 million births was made using Swedish population-based registers. The risk for adverse pregnancy outcomes was evaluated through logistic regression. Offspring with a mother or father with schizophrenia faced a doubled risk of infant mortality, which could not be explained by maternal behaviour alone during pregnancy. Excess infant death risk was largely attributable to post-neonatal death. Maternal factors (e.g. smoking) explained most of the other risks of adverse pregnancy outcomes among both mothers and fathers with schizophrenia. The risks to offspring whose fathers had schizophrenia suggest that, in addition to maternal risk behaviour, non-optimal social and/or parenting circumstances are of importance.


Grading of tenderness as a source of interrater error in the Ritchie articular index.
To assess the effect of grading of tenderness on the interrater reliability of the Ritchie articular index (RAI), 3 physicians recorded independent joint scores on each of 18 patients, examined in random order. Our results indicate that close agreement (Intraclass Correlation Coefficient = 0.85) can be achieved on global RAI scores, and that raters can achieve reasonable agreement (kappa = 0.40-0.59) on the absolute presence or absence of tenderness of individual joints. By contrast, interrater agreement hardly exceeds the chance level (kappa = 0.008-0.148) when degree of tenderness is independently assessed. The grading system of the RAI may thus be implicated as an important source of the instrument's interrater error.


Substrate Recognition by the Class II Lanthipeptide Synthetase HalM2.
Class II lanthipeptides belong to a diverse group of natural products known as ribosomally synthesized and post-translationally modified peptides (RiPPs). Most RiPP precursor peptides contain an N-terminal recognition sequence known as the leader peptide, which is typically recognized by biosynthetic enzymes that catalyze modifications on the C-terminal core peptide. For class II lanthipeptides, these are carried out by a bifunctional lanthipeptide synthetase (LanM) that catalyzes dehydration and cyclization reactions on peptidic substrates to generate thioether-containing, macrocyclic molecules. Some lanthipeptide synthetases are extraordinarily substrate tolerant, making them promising candidates for biotechnological applications such as combinatorial biosynthesis and cyclic peptide library construction. In this study, we characterized the mode of leader peptide recognition by HalM2, the lanthipeptide synthetase responsible for the production of the antimicrobial peptide haloduracin β. Using NMR spectroscopic techniques, in vitro binding assays, and enzyme activity assays, we identified substrate residues that are important for binding to HalM2 and for post-translational modification of the peptide substrates. Additionally, we provide evidence of the binding site on the enzyme using binding assays with truncated enzyme variants, hydrogen-deuterium exchange mass spectrometry, and photoaffinity labeling. Understanding the mechanism by which lanthipeptide synthetases recognize their substrate will facilitate their use in biotechnology, as well as further our general understanding of how RiPP enzymes recognize their substrates.


Long- and short-term variability of automated perimetry results in patients with optic neuritis and healthy subjects.
To measure the short- and long-term variability of automated perimetry in patients with optic neuritis and normal subjects. Prospective case-control design of patients with recovered optic neuritis with intraday and interday repetitions to obtain robust variability measurements. Entry criteria included a corrected pattern SD that was worse than the normal 5% probability level and a mean deviation worse than -3 dB but better than -20 dB. Five Humphrey 30-2 full threshold tests were administered during a 7-hour period (1 test every 2 hours) on the same day and at the same periods on 5 separate days. Seventeen patients with recovered optic neuritis and 10 healthy subjects of similar age. Short-term variability and long-term variability for global visual field data. Patients with optic neuritis demonstrated variations in visual field sensitivity that were outside the entire range of variability for normal controls. These variations occurred for multiple tests performed on the same day at specific times and for tests performed at specific times on different days. There were no consistent patterns of sensitivity changes that could be attributed to time of day. The most dramatic fluctuations occurred in a patient whose visual fields varied from normal to a hemianopic defect from one week to another and from a partial quadrant loss to a hemianopic defect at different times on the same day. Seven of the patients with optic neuritis also demonstrated intermittent vertical step defects. Patients with resolved optic neuritis can have large variations in visual field results on different days and at different times on the same day. The variations affect both the severity and the pattern of visual field loss and do not appear to be consistent across patients. These data indicate that care must be taken when automated visual field results in patients with optic neuritis are interpreted. Distinguishing systematic changes in sensitivity from variability requires more than a comparison of the current visual field with the most recent previous visual field.


Relative risks for stroke by age, sex, and population based on follow-up of 18 European populations in the MORGAM Project.
Within the framework of the MOnica Risk, Genetics, Archiving and Monograph (MORGAM) Project, the variations in impact of classical risk factors of stroke by population, sex, and age were analyzed. Follow-up data were collected in 43 cohorts in 18 populations in 8 European countries surveyed for cardiovascular risk factors. In 93 695 persons aged 19 to 77 years and free of major cardiovascular disease at baseline, total observation years were 1 234 252 and the number of stroke events analyzed was 3142. Hazard ratios were calculated by Cox regression analyses. Each year of age increased the risk of stroke (fatal and nonfatal together) by 9% (95% CI, 9% to 10%) in men and by 10% (9% to 10%) in women. A 10-mm Hg increase in systolic blood pressure involved a similar increase in risk in men (28%; 24% to 32%) and women (25%; 20% to 29%). Smoking conferred a similar excess risk in women (104%; 78% to 133%) and in men (82%; 66% to 100%). The effect of increasing body mass index was very modest. Higher high-density lipoprotein cholesterol levels decreased the risk of stroke more in women (hazard ratio per mmol/L 0.58; 0.49 to 0.68) than in men (0.80; 0.69 to 0.92). The impact of the individual risk factors differed somewhat between countries/regions with high blood pressure being particularly important in central Europe (Poland and Lithuania). Age, sex, and region-specific estimates of relative risks for stroke conferred by classical risk factors in various regions of Europe are provided. From a public health perspective, an important lesson is that smoking confers a high risk for stroke across Europe.


Do retained pediatric implants impact later total hip arthroplasty?
It is debated whether all pediatric implants in the proximal femur should be removed in childhood. Hardware removal requires an additional surgical procedure and may put the child at risk for postoperative fracture. However, the impact of retained pediatric implants on future surgeries such as total hip arthroplasty (THA) is not well-understood. We undertook this case-control study to evaluate the effect of retained pediatric implants on surgical complexity and complications at the time of THA. This may offer insight as to whether pediatric proximal femoral implants should be removed in childhood. Case-control study. Between 1990 and 2007, 15,601 primary THAs were performed at a tertiary referral center. Of those, 31 hips had pediatric hardware that had been implanted at a mean of 31 years before the time of THA. Perioperative course and complications were compared with an age-matched, sex-matched, and BMI-matched cohort of 31 patients with no retained implants. Mean follow-up after arthroplasty was 7 years. Operative time was significantly longer in the retained implant group compared with the control group (230 vs. 159 min; P<0.0001), as was the hospital stay (5.2 vs. 3.8 d; P=0.02). Four of the 14 patients with retained plates required a strut allograft at the time of primary THA. Revision femoral stems and bone grafting were more frequently required in the retained implant cohort. Estimated blood loss was also higher in the retained implant cohort (886 vs. 583 mL; P=0.031). Seven patients in the retained hardware group had a major complication, including intraoperative fracture (5), bleeding (1), and nerve injury (1), whereas no patients in the control group sustained major complications (P=0.017). Retained pediatric implants removed at the time of THA were associated with increased operative time, length of stay, and risk of intraoperative fracture. This data supports routine removal of proximal femoral implants in pediatric patients with a high likelihood of future THA. III, case-control study.


Pacing and Changes in Body Composition in 48 h Ultra-Endurance Running-A Case Study.
Pacing has been investigated in elite and master runners competing in marathon and ultra-marathon races up to 100 km and 100 miles, but not in longer ultra-marathons. In this case study, a 54-year-old master ultra-marathoner-intending to achieve as many kilometers as possible in a 48 h run-was examined. The changes in running speed during the race and selected anthropometric characteristics using bioelectrical impedance analysis (i.e., body mass and body water), during and after the race, were analyzed. The runner achieved a total distance of 230 km and running speed decreased non-linearly during the race. Body mass decreased, while percent body water increased, non-linearly, across the race. There was no statistically significant relationship between the decrease in body mass and the increase in percent body water. Considering the popularity of ultra-endurance running races, the findings of the present study offered valuable insight in the pacing and changes of body mass and body water during a 48 h run, and this information can be used by ultra-endurance runners and practitioners working with them.


[Effects of psychological status on external respiration in patients operated for nonspecific lung diseases].
Psychological tests and spirometry were used in examination of 39 patients operated on for severe chronic nonspecific pulmonary diseases. It was found that external respiration function was impaired more in emotionally strained subjects. Improvement of the external respiration coincided with diminution of hypochondria, positive changes in psychological status as a whole.


[The specific features of a pathogen in acutely progressive pulmonary tuberculosis].
Examination of 318 patients with different forms of acutely progressive pulmonary tuberculosis (APPT) revealed massive bacterial isolation in 181 patients of them. In one fourth of the patients, Mycobacterium tuberculosis (MBT) colonies grew during a month; the mean growth duration was 38.3 +/- 12.7 days, which was indicative of the viability of Mycobacteria and of their high virulence if they were isolated in large amounts. A hundred and thirty-three patients were found to be drug-resistant, which is one of the characteristics of present-day APPT. Such patients more frequently developed multidrug resistance. Sixty-three patients were ascertained to have secondary drug resistance, of them 41 patients were found to have drug resistance that progressed during APPT therapy.


[Features of anesthesia in surgical removal of insulinoma].
Presence of endocrine disorders, malfunction of liver and kidneys requests special approach application concerning general anaesthetic use in patients with the hormone producing insulinomas. There were 44 patients examined, in whom tumor was removed. Sodium hydroxybutyrate application while introducing anaesthesia promoted the haemodynamics stabilization. Arduan dosage ought to be reduced because of it possible cumulation in blood due to hepatorenal disorders existing in this patients. The dominance of the blood glucagon at the end of operation and the glucagon-insulin coefficient shift causes the tachycardia and the shock index increase. The proposed direct binasal stimulation of respiration after the anaesthesia conduction promoted rapid muscle tone and respiratory movements restoration in patients.


Validity and Reliability of Assessing Body Composition Using a Mobile Application.
The purpose of this study was to determine the validity and reliability of the LeanScreen (LS) mobile application that estimates percent body fat (%BF) using estimates of circumferences from photographs. The %BF of 148 weight-stable adults was estimated once using dual-energy x-ray absorptiometry (DXA). Each of two administrators assessed the %BF of each subject twice using the LS app and manually measured circumferences. A mixed-model ANOVA and Bland-Altman analyses were used to compare the estimates of %BF obtained from each method. Interrater and intrarater reliabilities values were determined using multiple measurements taken by each of the two administrators. The LS app and manually measured circumferences significantly underestimated (P < 0.05) the %BF determined using DXA by an average of -3.26 and -4.82 %BF, respectively. The LS app (6.99 %BF) and manually measured circumferences (6.76 %BF) had large limits of agreement. All interrater and intrarater reliability coefficients of estimates of %BF using the LS app and manually measured circumferences exceeded 0.99. The estimates of %BF from manually measured circumferences and the LS app were highly reliable. However, these field measures are not currently recommended for the assessment of body composition because of significant bias and large limits of agreements.


Does Coordinated Postpartum Care Influence Costs?
To investigate changes to health insurance costs for post-discharge postpartum care after the introduction of a midwife-led coordinated care model. The study included mothers and their newborns insured by the Helsana health insurance group in Switzerland and who delivered between January 2012 and May 2013 in the canton of Basel Stadt (BS) (intervention canton). We compared monthly post-discharge costs before the launch of a coordinated postpartum care model (control phase, n = 144) to those after its introduction (intervention phase, n = 92). Costs in the intervention canton were also compared to those in five control cantons without a coordinated postpartum care model (cross-sectional control group: n = 7, 767). The average monthly post-discharge costs for mothers remained unchanged in the seven months following the introduction of a coordinated postpartum care model, despite a higher use of midwife services (increasing from 72% to 80%). Likewise, monthly costs did not differ between the intervention canton and five control cantons. In multivariate analyses, the ambulatory costs for mothers were not associated with the post-intervention phase. Cross-sectionally, however, they were positively associated with midwifery use. For children, costs in the post-intervention phase were lower in the first month after hospital discharge compared to the pre-intervention phase (difference of -114 CHF [95%CI -202 CHF to -27 CHF]), yet no differences were seen in the cross-sectional comparison. The introduction of a coordinated postpartum care model was associated with decreased costs for neonates in the first month after hospital discharge. Despite increased midwifery use, costs for mothers remained unchanged.


P21 and P27 promote tumorigenesis and progression via cell cycle acceleration in seminal vesicles of TRAMP mice.
Transgenic adenocarcinoma mouse prostate (TRAMP) model is established to mimic human prostate cancer progression, where seminal vesicle lesions often occur and has been described as phyllodes-like epithelial-stromal tumors. However, the molecular mechanism regulating tumorigenesis and progression in seminal vesicles of TRAMP mice remains largely unknown. In this study, C57BL/6 TRAMP mice were found to have a significantly shorter lifespan than wild-type (WT) mice and all of the seminal vesicles were markedly increased in size and weight with age from 24 weeks exhibiting a clearly papillary-phyllode pattern, though no obvious difference was observed in multiple organs including heart, liver, spleen, lungs, kidneys, testicles and bone between TRAMP and WT mice, and less than 10% of TRAMP mice developed prostate tumors. Western blotting showed Cyclin (CCN) B1 and CCND1 were remarkably overexpressed in seminal vesicle tumors of TRAMP mice at 24 weeks of age and increased with age till the end of trial, which was confirmed by Immunohistochemistry (IHC). P21 and P27 were also significantly augmented, whereas P53 and phosphorylated P53 (p-P53) were constantly expressed in normal controls and P53 did not appear to be mutated. Not only cyclin-dependent kinase (CDK) 1 and phosphorylated forkhead box protein (FOX) O1 but also CDK4, CDK6 and phosphorylated retinoblastoma-associated protein (RB) had similar increase trends, so did epidermal growth factor receptor (EGFR), AKT serine/threonine kinase (AKT), and their respective phosphorylation levels. Signal transducer and activator of transcription (STAT) 3, p-STAT3, enhancer of zeste homolog 2 (EZH2) and EZH2 mediated trimethylation of histone H3 lysine 27 (H3K27me3) were considerably elevated, too. Taken together, this finding suggests P21 and P27 promote carcinogenesis and development in seminal vesicles of TRAMP mice via accelerating cell cycle progression, in which oncogenic transformation of P21 and P27 might be through regulation of EGFR-AKT signaling.


Resetting the sporulation rhythm in Pilobolus with short light flashes of high intensity.
The "clock-controlled" endogenous sporulation rhythm in the fungusPilobolus sphaerosporus has been investigated as part of a comparative study aimed at elucidating characteristic common features of circadian ((1)) rhythms. Pilobolus was chosen for inclusion in this study because of its demonstrated rhythm and sensitivity to light, and because it is a relatively simple plant. It has been shown that a single, high-intensity, 1/2000 second light flash will completely reset (shift the phase of) a rhythm persisting in continuous dim red light at constant temperature, and that one or more transient cycles occur before the phase shift is complete. The significance of these results is discussed.


Factors influencing adverse skin responses in rats receiving repeated subcutaneous injections and potential impact on neurobehavior.
Repeated subcutaneous (s.c.) injection is a common route of administration in chronic studies of neuroactive compounds. However, in a pilot study we noted a significant incidence of skin abnormalities in adult male Long-Evans rats receiving daily s.c. injections of peanut oil (1.0 ml/kg) in the subscapular region for 21 d. Histopathological analyses of the lesions were consistent with a foreign body reaction. Subsequent studies were conducted to determine factors that influenced the incidence or severity of skin abnormalities, and whether these adverse skin reactions influenced a specific neurobehavioral outcome. Rats injected daily for 21 d with food grade peanut oil had an earlier onset and greater incidence of skin abnormalities relative to rats receiving an equal volume (1.0 ml/kg/d) of reagent grade peanut oil or triglyceride of coconut oil. Skin abnormalities in animals injected daily with peanut oil were increased in animals housed on corncob versus paper bedding. Comparison of animals obtained from different barrier facilities exposed to the same injection paradigm (reagent grade peanut oil, 1.0 ml/kg/d s.c.) revealed significant differences in the severity of skin abnormalities. However, animals from different barrier facilities did not perform differently in a Pavlovian fear conditioning task. Collectively, these data suggest that environmental factors influence the incidence and severity of skin abnormalities following repeated s.c. injections, but that these adverse skin responses do not significantly influence performance in at least one test of learning and memory.


Corporate Social Responsibility and the Reciprocity Between Employee Perception, Perceived External Prestige, and Employees' Emotional Labor.
Corporate social responsibility (CSR) is emerging as a relevant subject in the business world and in the field of management research. Therefore, the current study incorporates classifications often used in organizational level CSR research that distinguish social responsibility relevant to its focus (internal and external), in proposing diverse routes that link various CSR practices (ie, internal and external) to employees' choice of emotional labor strategy (ie, via perceived organizational support and perceived external prestige). Data were collected from front-line employees of banks operating in Pakistan. Due to the study's focus on front-line employees, other personnel were excluded for data collection. We collected data through a self-administered questionnaire. The structural equation model (SEM) was employed on 376 valid responses using Smart-PLS3 to test the study hypotheses. After the analysis, we found satisfactory results for the fitness of both measurement and satisfactory models. Moreover, the results strongly support our proposed theoretical framework, and all proposed hypotheses were accepted. This study confirms that the perception of external prestige is a strong predictor of employees' emotions and relevant behaviors. Moreover, this study discusses under the light of social exchange theory that perceived organizational support strongly predicts employees' emotional labor, which diminishes the myth that prestige is the only factor to influence employees' emotions in the workplace. Moreover, this study negates the findings of Anwar et al that perceived external prestige does not have a significant negative effect on surface acting. It provides an insight not only for managers and researchers but also for society, especially in an Eastern workplace setting like Pakistan's banking sector.


Previous pregnancy outcome and breast density (United States).
We evaluated the association of pre-term delivery (PTD), low birth weight (LBW), and fetal death with breast density by age at mammogram and years since birth. Subjects were women aged < or =55 years who had a screening mammogram between 1 June 1996 and 1 August 1997 in Seattle, Washington, and whose records were linked to their previous state birth (1 January 1968 to 1 August 1997) or fetal death (1/1/1984-8/1/1997) records. We used unconditional logistic regression, adjusting for age at mammogram, body mass index, age at first birth, and menopausal status, to calculate the odds of dense (extremely or heterogeneously dense by BI-RADS) (n=3593) versus fatty breasts (scattered fibroglandular tissue or almost entirely fat) (n=2378) for women with a prior PTD (< 34, 34-36 versus > or =37 weeks gestation), LBW (< 2500 versus > or =2500 g), or fetal death (stillborn 20 weeks gestation versus live birth). The odds for denser breasts increased among women with PTD at <34 weeks gestation who were < or =45 years at time of mammogram (odds ratio (OR) and 95 confidence interval (CI)=2.8 (1.3-6.1)) and for whom <10 years had elapsed since pregnancy (OR=8.8 (1.7-45.8)). We observed similar increases in density among women with LBW (OR=3.3 (1.3-8.2)) when <10 years had elapsed. PTD and LBW may have a transitory effect on breast density.


Anatomical correlates to the bands seen in the outer retina by optical coherence tomography: literature review and model.
To evaluate the validity of commonly used anatomical designations for the four hyperreflective outer retinal bands seen in current-generation optical coherence tomography, a scale model of outer retinal morphology was created using published information for direct comparison with optical coherence tomography scans. Articles and books concerning histology of the outer retina from 1900 until 2009 were evaluated, and data were used to create a scale model drawing. Boundaries between outer retinal tissue compartments described by the model were compared with intensity variations of representative spectral-domain optical coherence tomography scans using longitudinal reflectance profiles to determine the region of origin of the hyperreflective outer retinal bands. This analysis showed a high likelihood that the spectral-domain optical coherence tomography bands attributed to the external limiting membrane (the first, innermost band) and to the retinal pigment epithelium (the fourth, outermost band) are correctly attributed. Comparative analysis showed that the second band, often attributed to the boundary between inner and outer segments of the photoreceptors, actually aligns with the ellipsoid portion of the inner segments. The third band corresponded to an ensheathment of the cone outer segments by apical processes of the retinal pigment epithelium in a structure known as the contact cylinder. Anatomical attributions and subsequent pathophysiologic assessments pertaining to the second and third outer retinal hyperreflective bands may not be correct. This analysis has identified testable hypotheses for the actual correlates of the second and third bands. Nonretinal pigment epithelium contributions to the fourth band (e.g., Bruch membrane) remain to be determined.


montalcino, A zebrafish model for variegate porphyria.
Inherited or acquired mutations in the heme biosynthetic pathway leads to a debilitating class of diseases collectively known as porphyrias, with symptoms that can include anemia, cutaneous photosensitivity, and neurovisceral dysfunction. In a genetic screen for hematopoietic mutants, we isolated a zebrafish mutant, montalcino (mno), which displays hypochromic anemia and porphyria. The objective of this study was to identify the defective gene and characterize the phenotype of the zebrafish mutant. Genetic linkage analysis was utilized to identify the region harboring the mno mutation. Candidate gene analysis together with reverse transcriptase polymerase chain reaction was utilized to identify the genetic mutation, which was confirmed via allele-specific oligo hybridizations. Whole mount in situ hybridizations and o-dianisidine staining were used to characterize the phenotype of the mno mutant. mRNA and morpholino microinjections were performed to phenocopy and/or rescue the mutant phenotype. Homozygous mno mutant embryos have a defect in the protoporphyrinogen oxidase (ppox) gene, which encodes the enzyme that catalyzes the oxidation of protoporphyrinogen. Homozygous mutant embryos are deficient in hemoglobin, and by 36 hours post-fertilization are visibly anemic and porphyric. The hypochromic anemia of mno embryos was partially rescued by human ppox, providing evidence for the conservation of function between human and zebrafish ppox. In humans, mutations in ppox result in variegate porphyria. At present, effective treatment for acute attacks requires the administration intravenous hemin and/or glucose. Thus, mno represents a powerful model for investigation, and a tool for future screens aimed at identifying chemical modifiers of variegate porphyria.


Cyclin D2 is essential for the compensatory beta-cell hyperplastic response to insulin resistance in rodents.
A major determinant of the progression from insulin resistance to the development of overt type 2 diabetes is a failure to mount an appropriate compensatory beta-cell hyperplastic response to maintain normoglycemia. We undertook the present study to directly explore the significance of the cell cycle protein cyclin D2 in the expansion of beta-cell mass in two different models of insulin resistance. We created compound knockouts by crossing mice deficient in cyclin D2 (D2KO) with either the insulin receptor substrate 1 knockout (IRS1KO) mice or the insulin receptor liver-specific knockout mice (LIRKO), neither of which develops overt diabetes on its own because of robust compensatory beta-cell hyperplasia. We phenotyped the double knockouts and used RT-qPCR and immunohistochemistry to examine beta-cell mass. Both compound knockouts, D2KO/LIRKO and D2KO/IRS1KO, exhibited insulin resistance and hyperinsulinemia and an absence of compensatory beta-cell hyperplasia. However, the diabetic D2KO/LIRKO group rapidly succumbed early compared with a relatively normal lifespan in the glucose-intolerant D2KO/IRS1KO mice. This study provides direct genetic evidence that cyclin D2 is essential for the expansion of beta-cell mass in response to a spectrum of insulin resistance and points to the cell-cycle protein as a potential therapeutic target that can be harnessed for preventing and curing type 2 diabetes.


The radioresponse of the central nervous system: a dynamic process.
Radiation continues to be a major treatment modality for tumors located within and close to the central nervous system (CNS). Consequently, alleviating or protecting against radiation-induced CNS injury would be of benefit in cancer treatment. However, the rational development of such interventional strategies will depend on a more complete understand-ing of the mechanisms responsible for the development of this form of normal tissue injury. Whereas the vasculature and the oligodendrocyte lineage have traditionally been considered the primary radiation targets in the CNS, in this review we suggest that other phenotypes as well as critical cellular interactions may also be involved in determining the radio-response of the CNS. Furthermore, based on the assumption that the CNS has a limited repertoire of responses to injury, the reaction of the CNS to other types of insults is used as a framework for modeling the pathogenesis of radiation-induced damage. Evidence is then provided suggesting that, in addition to acute cell death, radiation induces an intrinsic recovery/repair response in the form of specific cytokines and may


Late pregnancy suppresses relapses in experimental autoimmune encephalomyelitis: evidence for a suppressive pregnancy-related serum factor.
Women with multiple sclerosis have significantly diminished disease activity during pregnancy. The purpose of our study was to identify the underlying mechanism for the diminished disease activity. We found that during the period of late pregnancy there is protection against paralysis, during both the induction and effector phases of relapsing experimental autoimmune encephalomyelitis, a mouse model of multiple sclerosis. We did not find any changes in the cytokine secretion profiles or the proliferative activity of autoreactive T cells from mice induced during late pregnancy compared with virgin controls. In mice mated after disease onset, the inflammatory histologic lesions did not clear, despite marked clinical improvement during pregnancy. We found evidence for a serum factor present in late pregnancy that suppresses T cell activation. In the presence of sera taken from mice late in pregnancy, the proliferative response and IL-2 production of proteolipid protein p139-151-specific T cells were significantly diminished as compared with stimulation in the presence of normal mouse sera. In conclusion, serum from late pregnancy has the capacity to down-regulate T cell responses and might be associated with the amelioration of disease activity in experimental autoimmune encephalomyelitis.


The role of the cerebellum in cognition and emotion: personal reflections since 1982 on the dysmetria of thought hypothesis, and its historical evolution from theory to therapy.
The cognitive neuroscience of the cerebellum is now an established multidisciplinary field of investigation. This essay traces the historical evolution of this line of inquiry from an emerging field to its current status, with personal reflections over almost three decades on this journey of discovery. It pays tribute to early investigators who recognized the wider role of the cerebellum beyond motor control, traces the origins of new terms and concepts including the dysmetria of thought theory, the universal cerebellar transform, and the cerebellar cognitive affective syndrome, and places these developments within the broader context of the scientific efforts of a growing community of cerebellar cognitive neuroscientists. This account considers the converging evidence from theoretical, anatomical, physiological, clinical, and functional neuroimaging approaches that have resulted in the transition from recognizing the cerebellar incorporation into the distributed neural circuits subserving cognition and emotion, to a hopeful new era of treatment of neurocognitive and neuropsychiatric manifestations of cerebellar diseases, and to cerebellar-based interventions for psychiatric disorders.


Endo-exonuclease of human leukaemic cells: evidence for a role in apoptosis.
Inactive forms of endo-exonuclease, activated in vitro by treatment with trypsin, have been identified in human leukaemic CEM and MOLT-4 cells. They comprise over 95% of the total single-strand DNase activity in nuclei and are mainly bound to chromatin and the nuclear matrix. The activated enzyme had Mg2+(Mn2+)-dependent, Ca(2+)-stimulated activities with single- and double-strand DNAs and RNA (polyriboadenylic acid) and other properties characteristic of endo-exonucleases previously described. At least twice as much inactive endo-exonuclease has also been localised in extranuclear compartments of CEM and MOLT-4 cells, 85% bound to the membranes of the endoplasmic reticulum and 15% free in the cytosol. The soluble cytosolic trypsin-activatable endo-exonuclease was immunoprecipitated by antibodies raised independently to both Neurospora and monkey CV-1 cell endo-exonucleases. The free and bound enzymes of both nuclear and extranuclear compartments also cross-reacted on immunoblots with the antibody raised to Neurospora endo-exonuclease to reveal multiple polypeptides ranging in size from 18 to 145 kDa, many of which exhibited activity on DNA gels. The major species bound to the chromatin/matrix were in the 55-63 kDa range. Limited proteolysis of the large polypeptides to those of 18 to 46 kDa accompanied spontaneous chromatin DNA fragmentation to form DNA "ladders' in an isolated nuclei/cytosol system. When the leukaemic cells were treated in culture with either etoposide or podophyllotoxin to induce apoptosis, the largest polypeptides disappeared and smaller endo-exonuclease-related polypeptides of 18 to 46 kDa were detected in the nuclear extracts. The appearance of these polypeptides also correlated with extensive chromatin DNA fragmentation. In addition, there were correlations between the depletion of the major 55-63 kDa species bound to the membranes of the endoplasmic reticulum, depletion of the extranuclear trypsin-activatable activity and the onset and extent of chromatin DNA fragmentation in both cell lines. The extranuclear 55-63 kDa species may be precursors of the chromatin/matrix bound endo-exonuclease. The results indicate that endo-exonuclease plays a role in chromatin DNA degradation in mammalian cells during apoptosis.


Cholecystoduodenal fistula due to pancreatic carcinoma: CT diagnosis.
Spontaneous biliary-enteric fistula is almost always due to cholelithiasis or peptic ulcer disease; rarely is malignancy responsible. A patient with carcinoma of the pancreas who presented with gastrointestinal hemorrhage and pneumobilia due to a malignant cholecystoduodenal fistula is reported.


Hyperactive BMP signaling induced by ALK2(R206H) requires type II receptor function in a Drosophila model for classic fibrodysplasia ossificans progressiva.
Fibrodysplasia Ossificans Progressiva (FOP) is an autosomal dominant disorder characterized by episodic deposition of heterotopic bone in place of soft connective tissue. All FOP-associated mutations map to the BMP type I receptor, ALK2, with the ALK2(R206H) mutant form found in the vast majority of patients. The mechanism(s) regulating the expressivity of hyperactive ALK2(R206H) signaling throughout a patient's life is not well understood. In Drosophila, human ALK2(R206H) receptor induces hyperactive BMP signaling. As in vertebrates, elevated signaling associated with ALK2(R206H) in Drosophila is ligand-independent. We found that a key determinant for ALK2(R206H) hyperactivity is a functional type II receptor. Furthermore, our results indicate that like its Drosophila ortholog, Saxophone (Sax), wild-type ALK2 can antagonize, as well as promote, BMP signaling. The dual function of ALK2 is of particular interest given the heterozygous nature of FOP, as the normal interplay between such disparate behaviors could be shifted by the presence of ALK2(R206H) receptors. Our studies provide a compelling example for Drosophila as a model organism to study the molecular underpinnings of complex human syndromes such as FOP.


Expression of Biglycan in First Trimester Chorionic Villous Sampling Placental Samples and Altered Function in Telomerase-Immortalized Microvascular Endothelial Cells.
Biglycan (BGN) has reduced expression in placentae from pregnancies complicated by fetal growth restriction (FGR). We used first trimester placental samples from pregnancies with later small for gestational age (SGA) infants as a surrogate for FGR. The functional consequences of reduced BGN and the downstream targets of BGN were determined. Furthermore, the expression of targets was validated in primary placental endothelial cells isolated from FGR or control pregnancies. APPROACH AND RESULTS: BGN expression was determined using real-time polymerase chain reaction in placental tissues collected during chorionic villous sampling performed at 10 to 12 weeks' gestation from pregnancies that had known clinical outcomes, including SGA. Short-interference RNA reduced BGN expression in telomerase-immortalized microvascular endothelial cells, and the effect on proliferation, angiogenesis, and thrombin generation was determined. An angiogenesis array identified downstream targets of BGN, and their expression in control and FGR primary placental endothelial cells was validated using real-time polymerase chain reaction. Reduced BGN expression was observed in SGA placental tissues. BGN reduction decreased network formation of telomerase-immortalized microvascular endothelial cells but did not affect thrombin generation or cellular proliferation. The array identified target genes, which were further validated: angiopoetin 4 (ANGPT4), platelet-derived growth factor receptor α (PDGFRA), tumor necrosis factor superfamily member 15 (TNFSF15), angiogenin (ANG), serpin family C member 1 (SERPIN1), angiopoietin 2 (ANGPT2), and CXC motif chemokine 12 (CXCL12) in telomerase-immortalized microvascular endothelial cells and primary placental endothelial cells obtained from control and FGR pregnancies. This study reports a temporal relationship between altered placental BGN expression and subsequent development of SGA. Reduction of BGN in vascular endothelial cells leads to disrupted network formation and alterations in the expression of genes involved in angiogenesis. Therefore, differential expression of these may contribute to aberrant angiogenesis in SGA pregnancies.


[Application of early sutures in complex treatment of purulent wounds].
The examination and treatment of 841 patients with purulent diseases and acute purulent surgical diseases of soft tissues included 486 patients (control group) treated by a traditional (open) method and 355 patients (main group) treated by complex methods using early sutures. The primary suture was used in 124 patients. The average number of bed-days in this group of patients was (11.5 +/- 0.2) days. The primary delayed suture was used in 192 patients--the average number of bed-days was (12.8 +/- 0.1) days. The early secondary suture was used in 27 patients--the average number of bed-days was (17.3 +/- 0.4) days. In 327 (92.1%) cases of the main group patients the healing of the wounds by primary intention was obtained with good functional and cosmetic results which allowed to make the period of hospital treatment at an average 12.2 days shorter.


Prenuptial dental extractions in Acadian women: first report of a cultural tradition.
Prenuptial tooth extractions, extractions of all teeth in at least one dental arch before marriage, are not identified in the dental literature. Driven by a professional encounter, the purpose of this study was to confirm the existence of this practice among Acadian women. An 8-item survey instrument with space for comments was mailed to 182 dentists from traditionally Acadian regions of Canada. The survey was provided in English and French. Ninety dentists responded (50.3%); 8 of them (9%) had been asked to perform prenuptial extractions, and an additional 9 volunteered awareness of this practice. Awareness and requests were associated with dental practice in a county with a ≥20% French-speaking population. Prenuptial extractions in this population have been confirmed by the current cohort of dentists. The potential public health, clinical, and systemic health research implications for women who are edentulous for most of their adult life merit further study. Additionally, it is important to determine if interventions are needed to curtail cultural expectations of such practices.


Corneal-protective effects of an artificial tear containing sodium hyaluronate and castor oil on a porcine short-term dry eye model.
The corneal-protective effects of an artificial tear containing sodium hyaluronate (SH) and castor oil (CO) were evaluated on a porcine short-term dry eye model. Fresh porcine eyes with an intact cornea were treated with an artificial tear of saline, SH solution (0.1%, 0.5% or 1%), CO solution (0.5%, 1% or 5%) or a mixture solution containing 0.5% SH and 1% CO and then desiccated for 60, 90 or 180 min. To assess corneal damage, the eyes were stained with methylene blue (MB) or lissamine green (LG). The staining score of MB, absorbance of MB extracted from the cornea and staining density of LG increased significantly with increasing desiccation time in untreated and all artificial tear-treated eyes, although there were no significant differences in staining scores and absorbance of MB between eyes treated continuously with saline and 1% SH-treated ones at 60 and 90 min of desiccation or the mixture-treated eyes at 60 min of desiccation. No significant differences in the staining density of LG were also found between continuous saline-treated eyes and ones desiccated for 60 min and treated with 1% SH and the mixture. Mild cytoplasmic vacuolations were histopathologically observed in the basal and wing cells in eyes desiccated for 60 min and treated with 1% SH and the mixture. The mixture solution containing 0.5% SH and 1% CO has protective effects against corneal desiccation similar to those of 1% SH and would be helpful as an artificial tear.


Plasma B-type natriuretic peptide levels predict postoperative atrial fibrillation in patients undergoing cardiac surgery.
Postoperative (postop) atrial fibrillation (AF) occurs in up to 60% of patients after cardiac surgery, leading to longer hospital stays and increased healthcare costs. Recently, B-type natriuretic peptide (BNP) has been reported to predict occurrence of nonpostoperative AF. This study evaluates whether elevated preoperative (preop) plasma BNP levels predict the occurrence of postop AF. One hundred eighty-seven patients with no history of atrial arrhythmia who had a preoperative BNP level and had undergone cardiac surgery were identified. Their records were reviewed, and postoperative ECG and telemetry strips were analyzed for AF until the time of discharge. Postop AF was documented in 80 patients (42.8%). AF patients were older (68+/-11 versus 64+/-14 years, P=0.04), but there was no difference in sex distribution, hypertension, left ventricular (LV) function, LV hypertrophy (LVH), left atrial size, history of coronary artery disease (CAD), or beta-blocker use. Preop plasma BNP levels were higher in the postop AF patients (615 versus 444 pg/mL, P=0.005). After adjustment for age, sex, type of surgery, hypertension, LV function, LVH, left atrial size, CAD, and beta-blocker use, the odds ratios of postop AF according to increasing quartiles, compared with patients with lowest quartile, were 1.8, 2.5, and 3.7 (P(trend)=0.03). An elevated preop plasma BNP level is a strong and independent predictor of postop AF. This finding has important implications for identifying patients at higher risk of postop AF who could be considered for prophylactic antiarrhythmic or beta-blocker therapy.


Factors associated with shockable versus non-shockable rhythms in patients with in-hospital cardiac arrest.
To identify factors associated with the initial rhythm in patients with in-hospital cardiac arrest and to assess whether potential differences in outcomes based on the initial rhythm can be explained by patient and event characteristics. Adult patients (≥18 years old) with in-hospital cardiac arrest in 2017 and 2018 were included from the Danish In-Hospital Cardiac Arrest Registry (DANARREST). We used population-based registries to obtain data on comorbidities, cardiac procedures, and medications. Unadjusted and adjusted risk ratios (RRs) for initial rhythm, return of spontaneous circulation (ROSC), and survival were estimated in separate models including an incremental number of prespecified variables. A total of 3422 patients with in-hospital cardiac arrest were included, of which 639 (19%) had an initial shockable rhythm. Monitored cardiac arrest, witnessed cardiac arrest, and specific cardiac diseases (i.e. ischemic heart disease, dysrhythmias, and valvular heart disease) were associated with initial shockable rhythm. Conversely, higher age, female sex, and specific non-cardiovascular comorbidities (e.g. overweight and obesity, renal disease, and pulmonary cancer) were associated with an initial non-shockable rhythm. Initial shockable rhythm remained strongly associated with increased ROSC (RR = 1.63, 95%CI 1.51-1.76), 30-day survival (RR = 2.31, 95%CI 2.02-2.64), and 1-year survival (RR = 2.36, 95%CI 2.02-2.76) compared to initial non-shockable rhythm in the adjusted analyses. In this study, specific patient and cardiac arrest characteristics were associated with initial rhythm in patients with in-hospital cardiac arrest. However, differences in patient and cardiac arrest characteristics did not fully explain the association with survival for initial shockable rhythm compared to a non-shockable rhythm.


Estimating neuronal connectivity from axonal and dendritic density fields.
Neurons innervate space by extending axonal and dendritic arborizations. When axons and dendrites come in close proximity of each other, synapses between neurons can be formed. Neurons vary greatly in their morphologies and synaptic connections with other neurons. The size and shape of the arborizations determine the way neurons innervate space. A neuron may therefore be characterized by the spatial distribution of its axonal and dendritic "mass." A population mean "mass" density field of a particular neuron type can be obtained by averaging over the individual variations in neuron geometries. Connectivity in terms of candidate synaptic contacts between neurons can be determined directly on the basis of their arborizations but also indirectly on the basis of their density fields. To decide when a candidate synapse can be formed, we previously developed a criterion defining that axonal and dendritic line pieces should cross in 3D and have an orthogonal distance less than a threshold value. In this paper, we developed new methodology for applying this criterion to density fields. We show that estimates of the number of contacts between neuron pairs calculated from their density fields are fully consistent with the number of contacts calculated from the actual arborizations. However, the estimation of the connection probability and the expected number of contacts per connection cannot be calculated directly from density fields, because density fields do not carry anymore the correlative structure in the spatial distribution of synaptic contacts. Alternatively, these two connectivity measures can be estimated from the expected number of contacts by using empirical mapping functions. The neurons used for the validation studies were generated by our neuron simulator NETMORPH. An example is given of the estimation of average connectivity and Euclidean pre- and postsynaptic distance distributions in a network of neurons represented by their population mean density fields.


[Combined inhibiting action of new salicylic acid derivatives with alpha-tocopherol of the oxidation of methyl oleate].
The inhibitory action of compositions of alpha-tocopherol (alpha-TP) and salicylic acid derivatives on the process of initiated oxidation of methyl oleate (MO), alpha-TP and the salicilyc acid derivatives exhibited the synergistic affect, which was demonstrated by the methods of UV-spectroscopy and high-performance liquid chromatography (HPLC).


Comparative pathology of select agent influenza a virus infections.
Influenza A virus infections may spread rapidly in human populations and cause variable mortality. Two of these influenza viruses have been designated as select agents: 1918 H1N1 virus and highly pathogenic avian influenza (HPAI) virus. Knowledge of the pathology of these virus infections in humans, other naturally infected species, and experimental animals is important to understand the pathogenesis of influenza, to design appropriate models for evaluation of medical countermeasures, and to make correct diagnoses. The most important complication of influenza in humans is viral pneumonia, which often occurs with or is followed by bacterial pneumonia. Viremia and extrarespiratory disease are uncommon. HPAI viruses, including HPAI H5N1 virus, cause severe systemic disease in galliform species as well as in anseriform species and bird species of other orders. HPAI H5N1 virus infection also causes severe disease in humans and several species of carnivores. Experimental animals are used to model different aspects of influenza in humans, including uncomplicated influenza, pneumonia, and virus transmission. The most commonly used experimental animal species are laboratory mouse, domestic ferret, and cynomolgus macaque. Experimental influenza virus infections are performed in various other species, including domestic pig, guinea pig, and domestic cat. Each of these species has advantages and disadvantages that need to be assessed before choosing the most appropriate model to reach a particular goal. Such animal models may be applied for the development of more effective antiviral drugs and vaccines to protect humans from the threat of these virus infections.


The threat of micro/nanoplastic to aquatic plants: current knowledge, gaps, and future perspectives.
Plastics have been recognized as an emerging pollutant and have raised global concerns due to their widespread distribution in the environment and potential harm to living systems. However, research on the threat of micro/nanoplastics (MPs/NPs) to the unique group of aquatic plants is far behind, necessitating a comprehensive review to summarize current research progress and identify future research needs. This review explores the sources and distribution patterns of MPs/NPs in aquatic environments, highlighting their uptake by aquatic plants through roots and leaves, and subsequent translocation via the vascular system facilitated by the transpiration stream. Exposure to MPs/NPs elicits diverse effects on the growth, physiology, and ecological interactions of aquatic plants, with variations influenced by plastic properties, plant species, and experimental conditions. Furthermore, the presence of MPs/NPs can impact the toxicity and bioavailability of other associated toxicants to aquatic plants. This review shows critical knowledge gaps and emphasizes the need for future research to bridge the current understanding of the limitations and challenges posed by MPs/NPs in aquatic ecosystems.


Real-Time Fluoroscopic and C-Arm Computed Tomography Evaluation of Ommaya Reservoir Integrity.
We describe a case of a 24-year-old patient with relapsed acute myelogenous leukemia involving the central nervous system. After placement of an Ommaya reservoir for intrathecal chemotherapy administration, the patient developed progressive headache, nausea, and drowsiness and was found to have an enlarging subdural collection underlying the Ommaya. To exclude leakage of the Ommaya system into the subdural space, real-time fluoroscopic and C-arm computed tomographic evaluation of the Ommaya reservoir was performed after iodinated contrast injection into the reservoir. This novel technique demonstrated complete integrity of the Ommaya reservoir without evidence of blockage or leakage of the system. The patient underwent uncomplicated evacuation of the subdural collection without replacement of the Ommaya reservoir and made an excellent recovery. This technique for real-time interrogation of the Ommaya reservoir may have additional utility in the evaluation for Ommaya reservoir dysfunction.


Heterogeneous Phenotypes in Lipid Storage Myopathy Due to ETFDH Gene Mutations.
We present six novel patients affected by lipid storage myopathy (LSM) presenting mutations in the ETFDH gene. Although the diagnosis of multiple acyl-coenzyme-A dehydrogenase deficiency (MADD) in adult life is difficult, it is rewarding because of the possibility of treating patients with carnitine or riboflavin, leading to a full recovery. In our patients, a combination of precipitating risk factors including previous anorexia, alcoholism, poor nutrition, and pregnancy contributed to a metabolic critical condition that precipitated the catabolic state.In the present series of cases, five novel mutations have been identified in the ETFDH gene. We propose clinical guidelines to screen patients with LSM due to different defects, in order to obtain a fast diagnosis and offer appropriate treatment. In such patients, early diagnosis and treatment as well as avoiding risk factors are part of clinical management.Specific biochemical studies are indicated to identify the type of LSM, such as level of free carnitine and acyl-carnitines and studies or organic acidemia. Indeed, when a patient is biochemically diagnosed with secondary carnitine deficiency, a follow-up with appropriate clinical-molecular protocol and genetic analysis is important to establish the final diagnosis, since riboflavin can be supplemented with benefit if riboflavin-responsive MADD is present. In muscle biopsies, increased lipophagy associated with p62-positive aggregates was observed. The clinical improvement can be attributed to the removal of an autophagic block, which appears to be reversible in this LSM.


Regulation of oligodendrocyte cell survival and differentiation by ciliary neurotrophic factor, leukemia inhibitory factor, oncostatin M, and interleukin-6.
The regulation and maintenance of developmental lineages by trophic factors, both cell-mediated and soluble, is a key aspect of cellular differentiation in the nervous system. In this review we focus on oligodendrocytes and their progenitors and how differentiation and survival are regulated by four neuropoietic cytokines: ciliary neurotrophic factor, leukemia inhibitory factor, oncostatin M, and interleukin-6 (IL-6). We discuss how these cytokines act as "broad spectrum" factors. That is, how, even within a specific cell lineage, a given cytokine may have different effects on the target cells at various stages of differentiation.


Socio-demographic predictors of obesity among 12,975 adult ever married Egyptian women of reproductive age group: evidence from nationwide survey.
We aimed to explore the predictors associated with obesity among adult ever-married Egyptian women aged 20-49 years based on the Egyptian Demographic and Health Survey (EDHS). We included adult ever married women from the EDHS conducted in 2014 that initially recruited 21,903 women. Univariate and multivariable analysis was conducted to identify socio-demographic predictors of women's obesity. We included 12,975 Egyptian women. Among them, 76% of the total respondents were obese where as 24% were with normal body mass index (BMI). In multivariable analysis, the results revealed that increasing age, higher wealth index, listening to radio at least once a week and women with primary and secondary education were at significant odds of developing obesity (p < 0.05). However, we found no association between residence of participants and the frequency of watching television upon the development of obesity (p > 0.05). Appropriate and targeted interventions should be implemented among the Egyptian reproductive age women to reduce the obesity as well as non-communicable diseases load associated with obesity. National Health Service policy makers should take multilevel approach targeting high risk sub-groups to raise awareness and to provide prevention against obesity and the subsequent complications.