Photoinhibition and repair in Dunaliella salina acclimated to different growth irradiances.
The light-dependent rate of photosystem-II (PSII) damage and repair was measured in photoautotrophic cultures of Dunaliella salina Teod. grown at different irradiances in the range 50-3000 μmol photons · m-2· s-1. Rates of cell growth increased in the range of 50-800 μmol photons·m-2·s-1, remained constant at a maximum in the range of 800-1,500 μmol photons·m-2 ·s-1, and declined due to photoinhibition in the range of 1500-3000 μmol photons·m-2·s-1. Western blot analyses, upon addition of lincomycin to the cultures, revealed first-order kinetics for the loss of the PSII reaction-center protein (D1) from the 32-kDa position, occurring as a result of photodamage. The rate constant of this 32-kDa protein loss was a linear function of cell growth irradiance. In the presence of lincomycin, loss of the other PSII reaction-center protein (D2) from the 34-kDa position was also observed, occurring with kinetics similar to those of the 32-kDa form of D1. Increasing rates of photodamage as a function of irradiance were accompanied by an increase in the steady-state level of a higher-molecular-weight protein complex (≈ 160-kDa) that cross-reacted with D1 antibodies. The steady-state level of the 160-kDa complex in thylakoids was also a linear function of cell growth irradiance. These observations suggest that photodamage to D1 converts stoichiometric amounts of D1 and D2 (i.e., the D1/D2 heterodimer) into a ≈160-kDa complex. This complex may help to stabilize the reaction-center proteins until degradation and replacement of D1 can occur. The results indicated an intrinsic half-time of about 60 min for the repair of individual PSII units, supporting the idea that degradation of D1 after photodamage is the rate-limiting step in the PSII repair process.


Suppressor of cytokine signaling-1 and chemokine (C-X-C Motif) receptor 3 expressions are associated with caseous necrosis in granulomas from patients with tuberculous lymphadenitis.
We investigated the role of suppressor of cytokine signaling-1 (SOCS1) and SOCS3 molecules in lymph nodes from tuberculous lymphadenitis patients (LNTB). Fewer T cells were noted in LNTB cases, which also had raised chemokine (C-X-C motif) receptor 3 (CXCR3) levels. In addition, we observed a positive correlation between CXCR3 and SOCS1 expression. Our data suggest that upregulation of SOCS1 molecules may contribute to the dissemination of Mycobacterium tuberculosis from granulomas.


Micronucleus test in bone marrow of mice treated with 1-nitropropane, 2-nitropropane and cisplatin.
Micronucleus tests were carried out in bone marrow of mice treated with 1-nitropropane, 2-nitropropane and cisplatin. For 1-nitropropane and 2-nitropropane the results were negative. With cisplatin a dose-dependent increase in the number of polychromatic erythrocytes with micronuclei was observed. The lowest positive dose was 0.1 mg/kg (P less than 0.001, Mann-Whitney-Wilcoxon test). The hepatocarcinogen 2-nitropropane showed clastogenic activity in human lymphocytes in vitro in the presence of S9 (Bauchinger et al., 1987). The negative results in bone marrow suggest that short-lived genotoxic metabolites may be formed in the liver but do not reach the bone marrow.


In vitro screening of the effect of hydrazine derivatives on hepatic aryl hydrocarbon hydroxylase activity.
1. The effect of hydrazine derivatives on the in vitro hepatic microsomal aryl hydrocarbon hydroxylase activity was examined using Sprague-Dawley male rats. 2. All hydrazine derivatives examined have some degree of inhibition on hepatic aryl hydrocarbon hydroxylase activity. 3. The inhibitory effect is concentration dependent and is also dependent on the structural substitution of the hydrazines. The more lipophilic the derivative, the more potent the inhibition of aryl hydrocarbon hydroxylase activity.


miR-92a inhibits peritoneal dissemination of ovarian cancer cells by inhibiting integrin α5 expression.
Ovarian cancer is characterized by widespread peritoneal dissemination and ascites and has a cure rate of only 30%. As has been previously reported, integrin α5 plays a key role in the peritoneal dissemination of ovarian cancer. Our aim was to identify a new miRNA that regulates integrin α5 expression and analyze the therapeutic potential of targeting this miRNA. By using an IHC analysis, we proved that high integrin α5 expression correlates with a poor prognosis in Japanese patients with International Federation of Gynecology and Obstetrics stage III ovarian cancer. Based on an miRNA algorithm search, we identified hsa-mir-92a (miR-92a) as a candidate. The level of miR-92a expression was significantly inversely correlated with ITGA5 expression in various cancer cells. Transfection of precursor miR-92a reduced integrin α5 expression in ovarian cancer cells, which was accompanied by the inhibition of cancer cell adhesion, invasion, and proliferation. miR-92a overexpression reduced the luciferase activity of the ITGA5 3'-untranslated region, suggesting that ITGA5 mRNA is a direct target of miR-92a. In in vivo ovarian cancer xenografts, the enforced expression of miR-92a in HeyA-8 cells suppressed peritoneal dissemination. Although we still have a long way to go before an effective and nontoxic miRNA-based cancer therapy can be introduced into the clinic, the inhibition of integrin α5 expression by targeting miR-92a needs to be explored further for future applications in ovarian cancer treatment.


Leukocyte migration test (LMT) in patients with thyroid disease: the response to human thyroid subcellular fractions.
The response of circulating leukocytes to thyroid subcellular fractions was investigated in 19 patients with Graves' disease, 15 patients with Hashimoto's thyroiditis, 7 patients with toxic adenoma, 19 patients with nontoxic goiter and in 10 healthy students as control subjects. For this purpose, the leukocyte migration test of Soborg and Bendixen was performed against human crude thyroid extract (CTE), cell plasma membranes, nuclei, ribosomes, mitochondria and microsomes. Our results show positive LMT against: 1) CTE in patients with Graves' disease (61 +/- 13, p less than 0.001) and Hashimoto's thyroiditis (65 +/- 11, p less than 0.001) compared to controls (90 +/- 11); 2) cell plasma membranes in patients with Graves' disease (41 +/- 14, p less than 0.001) and Hashimoto's thyroiditis (64 +/- 21, p less than 0.05) compared to controls (88 +/- 19); 3) nuclei in patients with Graves' disease (53 +/- 25, p less than 0.001) and Hashimoto's thyroiditis (53 +/- 23, p less than 0.001) compared to controls (83 +/- 11). Our findings of circulating leukocytes sensitized to cell plasma membranes and nuclear fraction in patients with Graves' disease and Hashimoto's thyroiditis provide the additional information that these patients have a specific defect in immune-surveillance.


The release and transdermal penetration of baclofen formulated in a poloxamer lecithin organogel.
The purpose of this study was to evaluate the in vitro release and ex vivo penetration of baclofen following incorporation into a 2% poloxamer lecithin organogel. Franz cells were utilized for both the release and penetration studies. Semi-permeable dialysis membranes were used as the model skin for the penetration study. Baclofen release and penetration at predetermined time points were assessed using high-performamce liquid chromatographic analysis. Results demonstrated that baclofen release from the poloxamer lecithin organogel was significantly higher than its penetration through porcine skin. The amount of baclofen released by the poloxamer lecithin organogel was linear up to 12 hours. Approximately 20% of applied drug was released over the duration of the study period. In comparison with drug released, the ex vivo penetration of baclofen through porcine skin was very low with only minute detectable quantities (significantly less than 1%) after the 12-hour study period. These results suggest that the request to include baclofen into a compounded poloxamer lecithin organogel should be approached cautiously by compounding pharmacists.


Nerve conduction studies are safe in patients with central venous catheters.
It is unknown if central venous catheters bypass the skin's electrical resistance and engender a risk of nerve conduction study-induced cardiac arrhythmia. The objective of this study is to determine if nerve conduction studies affect cardiac conduction and rhythm in patients with central venous catheters. Under continuous 12-lead electrocardiogram monitoring, subjects with and without central venous catheters underwent a series of upper extremity nerve conduction studies. A cardiologist reviewed the electrocardiogram tracings for evidence of cardiac conduction abnormality or arrhythmia. Ten control subjects and 10 subjects with central venous catheters underwent the nerve conduction study protocol. No malignant arrhythmias or conduction abnormalities were noted in either group. Nerve conduction studies of the upper extremities, including both proximal stimulation and repetitive stimulation, do not appear to confer increased risk of cardiac conduction abnormality in those patients with central venous catheters who are not critically ill or have a prior history of arrhythmia. Muscle Nerve 56: 321-323, 2017.


Fish embryos are damaged by dissolved PAHs, not oil particles.
To distinguish the toxicity of whole oil droplets from compounds dissolved in water, responses of zebrafish embryos exposed to particulate-laden, mechanically dispersed Alaska North Slope crude oil (mechanically dispersed oil (MDO)) were compared to those of embryos protected from direct oil droplet contact by an agarose matrix. Most polycyclic aromatic hydrocarbons (PAHs) in MDO were contained in oil droplets; about 16% were dissolved. The agarose precluded embryo contact with particulate oil but allowed diffusive passage of dissolved PAHs. The incidence of edema, hemorrhaging, and cardiac abnormalities in embryos was dose-dependent in both MDO and agarose and the biological effects in these compartments were identical in character. Although mean total PAH (TPAH) concentrations in MDO were about 5-9 times greater than in agarose, dissolved PAH concentrations were similar in the two compartments. Furthermore, mean differences in paired embryo responses between compartments were relatively small (14-23%, grand mean 17%), typically with a larger response in embryos exposed to MDO. Therefore, the embryos reacted only to dissolved PAHs and the response difference between compartments is explained by diffusion. Averaged over 48 h, the estimated mean TPAH concentration in agarose was about 16% less than the dissolved TPAH concentration in MDO. Thus, PAHs dissolved from oil are toxic and physical contact with oil droplets is not necessary for embryotoxicity.


Torque generated by the flagellar motor of Escherichia coli while driven backward.
The technique of electrorotation was used to apply torque to cells of the bacterium Escherichia coli tethered to glass coverslips by single flagella. Cells were made to rotate backward, that is, in the direction opposite to the rotation driven by the flagellar motor itself. The torque generated by the motor under these conditions was estimated using an analysis that explicitly considers the angular dependence of both the viscous drag coefficient of the cell and the torque produced by electrorotation. Motor torque varied approximately linearly with speed up to over 100 Hz in either direction, placing constraints on mechanisms for torque generation in which rates of proton transfer for backward rotation are limiting. These results, interpreted in the context of a simple three-state kinetic model, suggest that the rate-limiting step in the torque-generating cycle is a powerstroke in which motor rotation and dissipation of the energy available from proton transit occur synchronously.


A nationwide study of prenatal exposure to illicit drugs and risk of neurodevelopmental disorders and disruptive behavioral disorders.
This cohort study aimed to examine the association between prenatal exposure to illicit drugs and neurodevelopmental and disruptive behavioral disorders (DBD) in children aged 7-12 years, using data from four national databases in Taiwan from 2004 to 2016. We linked parental and child IDs from the Taiwan Maternal and Child Health database to track children's health status from birth to at least age 7 and identify those diagnosed with neurodevelopmental disorders. The study included 896,474 primiparous women who gave birth between 2004 and 2009, with 752 pregnant women with illicit drug use history and 7520 matched women without. The results of the study showed that prenatal illicit drug exposure was significantly associated with the development of neurodevelopmental disorders and DBD in offspring. The adjusted hazard ratios for developmental delay, mild-to-severe intellectual disability, attention deficit hyperactivity disorder, and DBD were 1.54 (95 % CI: 1.21-1.95), 2.63 (95 % CI: 1.64-4.19), 1.58 (95 % CI: 1.23-2.03), and 2.57 (95 % CI: 1.21-5.48), respectively. Furthermore, prenatal exposure to methamphetamine increased the risk of neurodevelopmental disorders and DBD in offspring, while opioid use was significantly associated with a higher risk of three types of neurodevelopmental disorders, but not with DBD. The use of sedative hypnotic drugs alone was not associated with any increased risk of the three types of neurodevelopmental disorders or DBD. However, we found a significant interaction effect between prenatal illicit drug exposure and the use of sedative hypnotic drugs, which increased the risk of developmental delay.


Integrating circadian dynamics with physiological processes in plants.
The plant circadian clock coordinates the responses to multiple and often simultaneous environmental challenges that the sessile plant cannot avoid. These responses must be integrated efficiently into dynamic metabolic and physiological networks essential for growth and reproduction. Many of the output pathways regulated by the circadian clock feed back to modulate clock function, leading to the appreciation of the clock as a central hub in a sophisticated regulatory network. In this Review, we discuss the circadian regulation of growth, flowering time, abiotic and biotic stress responses, and metabolism, as well as why temporal 'gating' of these processes is important to plant fitness.


Brief Report: Hispanic Patients' Trajectory of Cancer Symptom Burden, Depression, Anxiety, and Quality of Life.
Background: Anxiety and depression symptoms are known to increase cancer symptom burden, yet little is known about the longitudinal integrations of these among Hispanic/Latinx patients. The goal of this study was to explore the trajectory and longitudinal interactions among anxiety and depression, cancer symptom burden, and health-related quality of life in Hispanic/Latinx cancer patients undergoing chemotherapy. Baseline behavioral assessments were performed before starting chemotherapy. Follow-up behavioral assessments were performed at 3, 6, and 9 months after starting chemotherapy. Descriptive statistics, chi-square tests, Fisher's exact tests, and Mann-Whitney tests explored associations among outcome variables. Adjusted multilevel mixed-effects linear regression models were also used to evaluate the association between HADS scores, follow-up visits, FACT-G scale, MDASI scale, and sociodemographic variables. Increased cancer symptom burden was significantly related to changes in anxiety symptoms' scores (adjusted β^ = 0.11 [95% CI: 0.02, 0.19]. Increased quality of life was significantly associated with decreased depression and anxiety symptoms (adjusted β^ = -0.33; 95% CI: -0.47, -0.18, and 0.38 adjusted β^= -0.38; 95% CI: -0.55, -0.20, respectively). Findings highlight the need to conduct periodic mental health screenings among cancer patients initiating cancer treatment.


Release of neuroendocrine products in the pulmonary circulation during intermittent hypoxia in isolated rat lung.
The aim of this study was to evaluate the release of neuroendocrine (NE) products into the pulmonary circulation during intermittent hypoxia (IH) in isolated buffer-perfused and ventilated rat lungs. Isolated single-pass perfused rat lungs were repeatedly ventilated with hypoxic (2% O(2)) and normoxic (21% O(2)) gases for 5-min intervals. Perfusate collected during the study was analysed for bombesin-like-peptides (BLPs) and serotonin. In addition, immunohistochemical evaluation of the neuropeptides calcitonin gene-related peptide (CGRP) and chromogranin A (CgA) in the lung was performed. During IH, perfusate levels of BLPs decreased compared to lungs ventilated with normoxic gas only. After 15 min of IH, perfusate levels of BLPs were significantly lower than at corresponding time in normoxic lungs (2.6+/-0.7 pg ml(-1) versus 9.2+/-1.9 pg ml(-1), p=0.036). No significant difference between the study groups was observed in perfusate levels of serotonin. Immunohistochemical evaluation of the lungs revealed significantly increased number of pulmonary NE cells immunoreactive for CGRP in IH ventilated lungs compared to controls (10.1+/-1.5 neuroepithelial bodies (NEBs) (cm(2))(-1) versus 5.0+/-1.5 NEBs (cm(2))(-1), p=0.032). No change in the immunoreactivity for CgA was observed. The present study suggests that intermittent periods of hypoxia are associated with a rapid physiological modulation of the release of NE products into the pulmonary circulation in an isolated rat lung model.


The light microscopic demonstration of hydroperoxidase-positive Phi bodies and rods in leukocytes in acute myeloid leukemia.
Unique fusiform or spindle-shaped particles (Phi bodies) and rods with hydroperoxidase (catalase and/or peroxidase) activity are present in human granulocyte precursors only in acute myelogenous leukemia (AML). These newly recognized particles are much more numerous and prominent than Auer rods. They may be rapidly and readily identified using the microscope in marrow or peripheral blood films when the procedures recommended in this paper for fixation, incubation for hydroperoxidase demonstration in 3,3'-diaminobenzidine (DAB)/H2O2 medium, copper salt treatment and counterstaining (optional) with the Papanicolaou method are employed. Films prepared in the same manner but treated with benzidine/H2O2 medium for myeloperoxidase did not reveal these particles. We believe that Phi bodies are pathognomonic of AML since they are almost invariably present in AML patients with active disease. Their presence serves to distinguish AML from acute lymphocytic leukemia and from chronic granulocytic leukemia in blast crisis. Since the particles disappear in disease remission and reappear upon relapse, the recommended procedure is not only useful in diagnosis but in guiding therapy. When a very rapid diagnosis is needed, it is not necessary to counterstain the preparations, but the nuclei, cytoplasm and plasmalemma can readily be observed in the granulocyte precursors when they are counterstained by the Papanicolaou method. This treatment does not diminish the clarity of the Phi bodies and rods which stain by virtue of their peroxidatic activity. This cytochemical diagnostic procedure should be considered for adoption by hematology laboratories.


Effect of treatment with vitamin D3 on the responses of the duodenum of spontaneously hypertensive rats to bradykinin and to potassium.
1. The diet of spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) and Wistar (NWR) rats was supplemented with either 2% calcium lactate in the drinking water or 12.5 micrograms vitamin D3 100 g-1 body weight daily by gavage, for 14 days. 2. The blood pressure of the SHR treated with either calcium or vitamin D decreased to the same levels as that of WKY and NWR. 3. The response to bradykinin of the SHR isolated duodenum, which is predominantly contractile, upon treatment with vitamin D (but not with calcium), became predominantly relaxant, approaching the normal behavior of the WKY and NWR duodenum. 4. The relaxant responses of the SHR and WKY duodenum to potassium were smaller than those of NWR, but treatment with vitamin D increased the response in all three rat strains. 5. It is concluded that, besides sharing the hypotensive effect of calcium, vitamin D treatment of SHR has an effect on the duodenum smooth muscle which might be due to calmodulin-dependent activation of calcium-dependent potassium channels.


Optimisation of ICP-MS collision/reaction cell conditions for the determination of elements likely to be interfered (V, Cr, Fe, Co, Ni, As and Se) in foodstuffs.
A strategy for the accurate determination in foodstuffs of seven elements liable to be interfered with (V, Cr, Fe, Co, Ni, As and Se), was successfully applied. Firstly, to reduce spectroscopic interferences, four influential factors (hexapole and quadrupole bias, helium and hydrogen flows) of the collision/reaction cell device were optimised through the experimental design methodology. Secondly, non-spectroscopic interferences, which may severely disturb the analysis of matrices containing large amounts of non-target elements, were significantly reduced by a limited decrease in the flow rate of the optimum initial nebuliser rather than with a specific time-consuming dilution. Finally, the optimised multi-element method was subjected to a full validation that demonstrated its acceptable analytical performance.


Tissue engineering of white adipose tissue using hyaluronic acid-based scaffolds. I: in vitro differentiation of human adipocyte precursor cells on scaffolds.
Reconstruction of soft tissue defects is a challenge in plastic surgery and there is clinical need for adequate solutions. Aim of this study was to develop a biohybrid construct consisting of hyaluronic acid-based scaffolds and human adipocyte precursor cells as a soft tissue filler. Human adipocyte precursor cells were obtained by collagenase digestion of adipose tissue samples and seeded on hyaluronic acid-based spongy scaffolds of various degrees of esterification and pore size using different techniques. After cell attachment, adipose differentiation was induced by defined adipogenic factors under serum-free culture conditions. Among the five different scaffold types under investigation the highest cell attachment rate was observed for the HYAFF scaffold with 100% esterification and a mean pore size of 400microm (HYAFF 11lp). For inoculation of human adipocyte precursor cells on hyaluronic acid-based scaffolds a "drop-on" technique and low-pressure centrifugation using a Speed Vac airfuge were compared. With respect to efficacy, cell distribution and simpleness the drop-on method proved to be the method of choice. In a serum-free medium supplemented with 66nM insulin, 100nM cortisol and 1microg/ml troglitazone a substantial proportion of cells underwent adipose differentiation as assessed by lipid accumulation and emergence of glycerol-3-phosphate dehydrogenase activity, a lipogenic marker enzyme. Hyaluronic acid-based scaffolds appear to be a suitable three-dimensional carrier for the culture and in vitro differentiation of human adipocyte precursor cells.


Cholecalciferol (vitamin D3) inhibits growth and invasion by up-regulating nuclear receptors and 25-hydroxylase (CYP27A1) in human prostate cancer cells.
Epidemiological evidence suggests an inverse relationship between prostate cancer and serum vitamin D levels. We examined the ability of cholecalciferol (vitamin D(3)), a calcitriol precursor, to inhibit or reverse cellular changes associated with malignant transformation and invasion and explored its mechanisms of action. The RWPE2-W99 human prostate epithelial cell line, which forms slow-growing tumors in nude mice, was used because it mimics the behavior of the majority of primary human prostate cancers. Cholecalciferol, at physiological levels: (i) inhibited anchorage-dependent and -independent growth; (ii) induced differentiation by decreasing vimentin expression with a concomitant decrease in motility/chemotaxis; (iii) decreased MMP-9 and MMP-2 activity with concomitant decrease in invasion; and (iv) exerted its effects by up-regulating vitamin D receptor (VDR), retinoid-X receptor-alpha (RXR-alpha), and androgen receptor (AR) in a dose-dependent manner. Furthermore, we found that RWPE2-W99 prostate cancer cells, similar to RWPE-1 cells (Tokar and Webber. Clin Exp Metast 2005; 22: 265-73), constitutively express the enzyme 25-hydroxylase CYP27A1 which is markedly up-regulated by cholecalciferol. Cholecalciferol has effects similar to those of calcitriol on growth, MMP activity, and VDR. The ability of CYP27A1 to catalyze the conversion of cholecalciferol to 25(OH)D(3) and of 25(OH)D(3) to calcitriol has been reported. RWPE2-W99 cells, similar to RWPE-1 cells, appear to have the rare ability to locally convert cholecalciferol to the active hormone calcitriol. Because it can inhibit cellular changes associated with malignant transformation and invasion, we propose that cholecalciferol may be an effective agent for the treatment of prostate cancer.


Highly conserved nucleotide motifs present in the 5'UTR of the heme-receptor gene shmR are required for HmuP-dependent expression of shmR in Ensifer meliloti.
Heme may represent a major iron-source for bacteria. In the symbiotic nitrogen-fixing bacterium Ensifer meliloti 1021, iron acquisition from heme depends on the outer-membrane heme-receptor ShmR. Expression of shmR gene is repressed by iron in a RirA dependent manner while under iron-limitation its expression requires the small protein HmuP. In this work, we identified highly conserved nucleotide motifs present upstream the shmR gene. These motifs are widely distributed among Alpha and Beta Proteobacteria, and correlate with the presence of HmuP coding sequences in bacterial genomes. According to data presented in this work, we named these new motifs as HmuP-responsive elements (HPREs). In the analyzed genomes, the HPREs were always present upstream of genes encoding putative heme-receptors. Moreover, in those Alpha and Beta Proteobacteria where transcriptional start sites for shmR homologs are known, HPREs were located in the 5'UTR region. In this work we show that in E. meliloti 1021, HPREs are involved in HmuP-dependent shmR expression. Moreover, we show that changes in sequence composition of the HPREs correlate with changes in a predicted RNA secondary structure element and affect shmR gene expression.


Alcohol policies and alcohol-attributable cancer mortality in U.S. States.
Although more restrictive alcohol control policies (e.g., higher alcohol taxes) are related to lower levels of alcohol consumption, little is known about the relationship between alcohol policies and rates of alcohol-attributable cancer. State alcohol policy restrictiveness, as measured by a validated policy scale, were related to state rates of six alcohol attributable cancers in the U.S. from 2006 to 2010 in a lagged, cross-sectional linear regression that controlled for a variety of state-level factors. Cancer mortality rates were from the Center for Disease Control and Prevention's Alcohol-Related Disease Impact application, which uses population-attributable fraction methodology to calculate mortality from cancers of the esophagus, larynx, liver, oropharynx, prostate (male only) and breast (female only). More restrictive state alcohol policies were associated with lower cancer mortality rates for the six cancer types overall (beta [β] -0.33; 95% confidence interval [CI] -0.59, -0.07), and among men (β -0.45; 95% CI -0.81, -0.10) and women (β -0.21; 95% CI -0.40, -0.02). A 10% increase in the restrictiveness of alcohol policies (based on the mean APS among states) was associated with an 8.5% decrease in rates of combined alcohol-attributable cancers. In all analyses stratified by cancer subtype and sex, the associations were in the hypothesized direction (i.e., more restrictive state policy environments were associated with lower rates of alcohol-attributable cancers), with the exception of laryngeal cancer among women. Strengthening alcohol policies is a promising prevention strategy for alcohol-related cancer.


Occurrence and risk factors associated with gastrointestinal parasitism in horses reared in different systems.
To facilitate exploration of the immense range of gastrointestinal parasites in horses and the impact of parasitism on equine health, the present study aimed to evaluate the occurrence and risk factors associated with these infections in horses reared in different management systems in the state of Santa Catarina, Brazil. Samples were collected from 208 horses: 91 from extensive, 64 from semi-extensive, and 53 from intensive rearing systems. The identified helminths included those of the Strongylida order (80.29%), Parascaris equorum (3.36%), Oxyuris equi (4.33%), and Anoplocephala spp. (1.92%). By analyzing the coproculture results to differentiate among Strongylida order parasites, species such as Strongylus vulgaris, S. edentatus, S. equinus, Triodontophorus spp., and Trichostrongylus axei, in addition to members of the Cyathostominae subfamily, which include Gyalocephalus capitatus and Poteriostomum spp., were identified. The only positive sample of protozoa was that of Cryptosporidium spp. (13%). Regarding the rearing system, animals in the extensive system had a higher proportion of infected horses and a higher chance of infection than those in the other systems. For the variable co-grazing with cattle, only cyathostomins showed a significant difference with relatively low infection risk in co-grazing. Overall, the present study demonstrated a high occurrence of equine gastrointestinal parasites, especially those of the Strongylida order, with emphasis on small strongylids. In addition, analyzing factors associated with infection showed that management variables are important for controlling parasitism in horses.


Metal Complexes for Cancer Sonodynamic Therapy.
Sonodynamic therapy (SDT) for cancer treatment is gaining attention owing to its non-invasive property and ultrasound's (US) deep tissue penetration ability. In SDT, US activates the sonosensitizer at the target deep-seated tumors to generate reactive oxygen species (ROS), which ultimately damage tumors. However, drawbacks such as insufficient ROS production, aggregation of sonosensitizer, off-target side effects, etc., of the current organic/nanomaterial-based sonosensitizers limit the effectiveness of cancer SDT. Very recently, metal complexes with tunable physiochemical properties (such as sonostability, HOMO to LUMO energy gap, ROS generation ability, aqueous solubility, emission, etc.) have been devised as effective sonosensitizers, which could overcome the limitations of organic/nanomaterial-based sonosensitizers. This concept introduces all the reported metal-based sonosensitizers and delineates the prospects of metal complexes in cancer sonodynamic therapy. This new concept of metal-based sonosensitizer can deliver next-generation cancer drugs.


Biomagnification of cycad neurotoxins in flying foxes: implications for ALS-PDC in Guam.
Beta-methylamino-L-alanine (BMAA) occurs in higher levels in museum specimens of the Guamanian flying fox than in the cycad seeds the flying foxes feed on, confirming the hypothesis that cycad neurotoxins are biomagnified within the Guam ecosystem. Consumption of a single flying fox may have resulted in an equivalent BMAA dose obtained from eating 174 to 1,014 kg of processed cycad flour. Traditional feasting on flying foxes may be related to the prevalence of neuropathologic disease in Guam.


Neurocutaneous melanocytosis presenting in a teenager: A case report and review of the literature.
Neuro cutaneous melanocytosis (NCM) is a non-familial, congenital disorder characterized by multiple congenital nevi and brain or leptomeningeal abnormal melanin deposits. Here, we present an adult onset NCM. A 17-year-old boy presented with headache and double vision for 1 month. Magnetic resonance imaging of the brain showed hydrocephalus and abnormal meningeal hyper intensities in supra and infratentorial regions predominantly in the posterior fossa. Para medullary region showed an 11×10 mm nodular contrast enhancing nodule. Resection of an intramedullary central nervous system lesion revealed melanoma while skin biopsy was benign melanocytic nevus. As per Kadonaga and Frieden criteria, a diagnosis of NCM was made. Planned for craniospinal irradiation by three-dimensional conformal radiotherapy with a dose of 36 Gy, in 18 fractions (2 Gy/fraction and 5 days in a week) along with steroids however patient progressed and developed quadriplegia with intradural metastasis.


Prostate carcinoma: mitogenic stimulation of lymphocytes with phytohemagglutinin.
Lymphocyte transformation in response to mitogenic stimulation with PHA was studied in 46 patients with carcinoma of the prostate who have been followed for more than 3 years. This was related to clinical stage and histologic grade to form a prognostic index to forecast the natural history of this disease.


Spinal and peripheral modulation of gastric acid secretion and arterial pressure by neuropeptide Y, peptide YY, and pancreatic polypeptide in rats.
Spinal and peripheral modulation of pentagastrin-stimulated gastric acid secretion by the pancreatic polypeptide-fold (PP-fold) peptides, neuropeptide Y (NPY), peptide YY (PYY), and pancreatic polypeptide (PP), in urethane-anesthetized rats was evaluated. Neuropeptide Y, PYY, and PP (400 pmol) were administered via intravenous (IV) and intrathecal (IT) injections. The alpha 2 antagonist, yohimbine, was used to evaluate the role of the alpha 2 adrenergic receptors in the modulation of pentagastrin-stimulated gastric acid secretion by NPY, PYY, and PP. Peptide YY and PP (IV) rapidly increased pentagastrin-stimulated gastric acid secretion. Peptide YY and PP (IT) increased pentagastrin-stimulated gastric acid secretion following administration into the thoracic (T8-T10) region of the spinal cord. The alpha 2 adrenergic receptor antagonist, yohimbine, did not modify the increases in pentagastrin-stimulated gastric acid secretion following PYY and PP (IV or IT) administration. Neuropeptide Y (IT) decreased pentagastrin-stimulated gastric acid secretion. However, in the presence of alpha 2 adrenergic receptor blockade, pentagastrin-stimulated gastric acid secretion was potentiated by NPY (IT) administration. Therefore, the inhibitory effect of NPY (IT) on pentagastrin-stimulated gastric acid secretion required the activation of alpha 2 adrenergic receptors in the spinal cord of rats. Mean arterial blood pressure (MAP) was increased immediately following NPY and PYY (IV) administration. During the same time period, PP (IV) decreased MAP in anesthetized rats. Mean arterial blood pressure was rapidly increased by NPY and PYY (IT) in anesthetized rats. The increase in MAP following PYY (IT) was partially attenuated in the presence of yohimbine.(ABSTRACT TRUNCATED AT 250 WORDS)


Astrocytoma cell interaction with elastin substrates: implications for astrocytoma invasive potential.
Elastin has been identified within the meninges and the microvasculature of the normal human brain. However, the role that elastin plays in either facilitating astrocytoma cell attachment to these structures or modulating astrocytoma invasion has not been previously characterized. We have recently shown that astrocytoma cell lines and specimens produce tropoelastin, and express the 67 kDa elastin binding protein (EBP). In the present report, we have established that astrocytoma cells attach to elastin as a substrate in vitro. The U87 MG astrocytoma cell line demonstrated the greatest degree of adhesion. In addition, all astrocytoma cell lines examined were capable of penetrating and migrating through an intact elastin membrane, and of degrading tritiated-elastin, a process that could be prevented by the pre-incubation of astrocytoma cells with EDTA, but not with alpha1-antitrypsin. Astrocytoma cells were also capable of penetrating 1 mm sections of human brain tissue maintained as organotypic cultures. Interestingly, the invasive potential of cultured astrocytoma cells plated on organotypic cultures of human brain was significantly increased after exposure to elastin degradation products (kappa-elastin), which interact with astrocytoma cell surface EBP. Our data show that astrocytoma cells express a functional 67 kDa EBP, enabling them to potentially recognize and attach to elastin as a substrate. These data also suggest that this elastin receptor may be involved in processes which regulate regional astrocytoma invasion.


Acne keloidalis nuchae and hypertension in black subjects: a case-control study.
The aim of this case-control study was to look for an association between hypertension and acne keloidalis nuchae (AKN) in black subjects. We recruited 303 consenting subjects comprising 101 patients with AKN and 202 controls, case-matched by age (± 5 years). The mean patients age was 34.9 ± 10.7 years versus 35.6 ± 11.2 years for controls. The average duration of AKN progression in cases prior to consultation was 1831 days (5 years). The most frequently observed AKN lesions were papules (73/101; 72.3%), fibrous scars (42/101; 41.6%) and folliculitis/pustules (41/101; 40.6%). In terms of quality of life, the mean score of dermatology life quality index was 8.3 ± 5.2 (extremes: 0 to 22). In multivariate analysis, having a BMI of 25 kg/m2 or more (OR = 4.91; p < 0.001) and having systolic hypertension (OR = 1.22; p = 0.010) were associated with AKN.


Studies on Tanapox virus.
Virus characterization studies were performed to meliorate the taxonomic status of three currently unclassified, serologically related viruses: Tanapox virus (causes vesicular skin lesions in humans), Yaba-like disease (YLD) virus (causes vesicular skin lesions in monkeys), and Yaba monkey tumor virus (YMTV, causes epidermal histiocytoma). These studies included (1) microscopic observations of Tanapox virus cytopathic effect and morphogenesis during its 6-day cytolytic-type growth at 35 degrees in CV-1 monkey kidney cells; (2) resolution of Tanapox virion proteins by sodium dodecyl sulfate-polyacrylamide gel electrophoresis of nonenveloped and double-enveloped virus particles purified by velocity sedimentation in sucrose and CsCl density gradients; and (3) restriction endonuclease DNA comparison of the three viruses. DNA analysis showed that six recent Tanapox virus isolates from patients in Zaire, Africa, were identical to Tanapox virus, Kenya strain, from 1957 from a patient in the Tana River Valley. In addition, BamHI, MluI, and PstI cleavage sites mapped on the DNA of Kenya Tanapox virus, and PstI sites mapped on DNA of YLD virus differentiated YLD and Tanapox viruses as separate strains. On the other hand, YMTV shared few restriction endonuclease sites with Tanapox and YLD viruses, although all three cross-hybridized extensively. These studies along with published viral characteristics, support the formation of a new poxvirus genus: the suggested name is Yatapoxvirus, and the genus currently comprises two species, Tanapox virus and YMTV.


Ultra-trace analysis of multiple endocrine-disrupting chemicals in municipal and bleached kraft mill effluents using gas chromatography-high-resolution mass spectrometry.
A comprehensive gas chromatographic-high-resolution mass spectrometric (GC-HRMS)-based method was developed that permitted the simultaneous determination of 30 estrogenic endocrine-disrupting chemicals (EDCs) and related compounds, including surfactants, biogenic and synthetic steroids, fecal sterols, phytoestrogens, and plasticizers, in wastewater. Features of the method include low sample volume (~40 ml), optimized Florisil cleanup to minimize matrix interferences and optimized analyte derivatization to improve sensitivity via GC-HRMS. Detection limits were in the low- to mid-ng/L range, and recoveries were greater than 60% for most target analytes. This new method allows for high throughput analysis of many organic wastewater contaminants in a complex matrix with relative standard deviation of less than 15% for most measurable compounds. The applicability of the method was demonstrated by examining wastewater samples from different origins. Compounds such as di(2-ethylhexyl)phthalate, cholesterol, cholestanol, and other cholesterol derivatives were measured in much higher concentrations in untreated sewage and were reduced substantially in concentration by the treatment process. However, steroidal compounds, particularly estrone (E1), 17beta-estradiol (E2), and estriol (E3), as well as plant sterols (except stigmastanol), were greater in the treated municipal wastewater versus the untreated effluent. Plant and fungi sterols, stigmastanol and ergosterol, were found largely associated with bleached kraft mill effluent (BKME) as compared to the municipal effluents.


Landscape of Immunotherapy in Genitourinary Malignancies.
The past decade has witnessed a revolution in the development of immune checkpoint inhibitors for the treatment of multiple tumor types, including genitourinary cancers. Immune checkpoint inhibitors have notably improved the treatment outcomes of patients with metastatic renal cell carcinoma and metastatic urothelial carcinoma. In prostate cancer, the role of immunotherapy with checkpoint inhibitors is not yet established except for microsatellite instability high (MSI-H) tumors. Other immunotherapeutic approaches that have been explored in these malignancies include cytokines, vaccines, and cellular therapy. Ongoing studies are exploring the use of immunotherapy combinations as well as combination with chemotherapy and targeted therapy in these types of tumors. The use of immunotherapy beyond the metastatic setting is an active area of research. Moreover, there is great interest in biomarker development to predict response to immunotherapy and risk of toxicity. This book chapter is a comprehensive review of immunotherapeutic approaches, both approved and investigational, for the treatment of renal cell carcinoma, urothelial carcinoma, and prostate cancer.


Dietary Intakes of Patients with Alcohol Use Disorder During a 4-Week Protocol on an Inpatient Treatment Unit Found to Meet Dietary Reference Intakes for Macronutrients, but Have Variability in Energy Balance and Adequacy of Micronutrient Intake.
Despite literature supporting the importance of diet during rehabilitation, minimal research quantifies dietary intake during treatment for alcohol use disorder (AUD). The aim was to quantify dietary intake and energy balance of patients with AUD during inpatient treatment. This was a secondary analysis of data from a 4-week observational protocol. Participants self-selected food from a room service menu. Dietary intake was recorded by patients and reviewed by nutrition staff. To quantify nutrient and food group intake, data were coded into Nutrition Data Systems for Research software, versions 2016 and 2017. Daily average intake was calculated for all dietary variables. Participants (n = 22) were adults seeking treatment for AUD at the National Institutes of Health Clinical Center (Bethesda, MD) between September 2016 and September 2017 and who were enrolled in a study examining the microbiome during AUD rehabilitation. Four participants discontinued protocol participation before study week 4 and were not included in analyses examining change over time. Weight change, daily energy, and macronutrient and select micronutrient intakes were the main outcome measures included. Mean differences in intake and weight were assessed using nonparametric tests. Sixty-four percent of participants were male; mean ± SD age was 46.3 ± 13.0 years, mean ± SD body mass index (calculated as kg/m2) was 23.9 ± 2.5, and mean intake was 2,665 kcal/d (consisting of 45.9% carbohydrate, 34.9% fat, and 19.1% protein). Eighty percent or more of this sample met the Estimated Average Requirement for 10 of 16 micronutrients assessed. Male participants consumed more energy than estimated needs (P = .003) and gained a mean ± SD of 2.67 ± 1.84 kg (P = .006) when an outlier with weight loss and acute pancreatitis was removed from analysis. Female participants did not gain weight or consume more than estimated energy needs. Overall macronutrient intake was within recommended ranges, but intake of other dietary components and weight gain were variable, supporting the need for individualized nutrition care during AUD treatment.


Functional effects of lesion-induced plasticity: long term potentiation in formal and lesion-induced temporodentate connections.
The crossed temporodentate pathway from the entorhinal cortex of one hemisphere which proliferates in response to a contralateral entorhinal lesion in adult rats was analyzed for its ability to exhibit long term potentiation of synaptic efficacy similar to that which occurs in the normal ipsilateral temporodentate pathway. It was found that while the small synaptic response evoked by contralateral entorhinal cortical stimulation in normal rats does not undergo long term potentiation, after unilateral entorhinal lesions and proliferation of the crossed temporodentate pathway, the crossed pathway acquires a capacity for potentiation of synaptic action which qualitatively resembles that of the normal ipsilateral temporodentate circuit. However, despite the potentiation of synaptic drive, no long term enhancement of cell discharge was observed in the re-innervated dentate gyrus even through potentiation of this parameter was very prominent in the ipsilateral pathway. Mechanisms are discussed by which a previously non-potentiating pathway may acquire, as a consequence of lesion-induced sprouting, an ability to undergo long term potentiation of synaptic efficacy in a fasion similar to the ablated pathway. Reasons for the failure to observe potentiation of cell firing are also considered.


Spectral resolution in clinical magnetic resonance spectroscopy.
We observe linewidths of 0.1-0.4 ppm in 31P spectra of human muscle, liver, and brain. T2 measurements of muscle phosphocreatine, together with previous brain studies, indicate that further improvements in linewidth to 0.02-0.05 ppm might often be achieved, but in some lesions magnetic susceptibility variations may limit spectral resolution.


Inguinal Hernia Repairs on the Chief's Service: A Safe Educational Model in Resident Entrustment.
We hypothesized that a Chief Resident Service educational model provides safe care for patients compared to that received on standard academic services where rotating residents adopt the practices and preferences of their attending. We retrospectively identified patients undergoing inguinal hernia repairs from July 2016 through June 2019 and matched Chief's service patients to standard academic service patients 1:1 on CPT, sex and age. We compared patient characteristics, recurrence rates, outcomes and complications. Tertiary care center, single institution. Overall, 77 patients undergoing inguinal hernia repairs (66% open and 34% laparoscopic) on the Chief's service matched successfully to 77 standard academic service patients during the study period. Age, BMI and ASA were similar between the services, but Chief's service patients were less likely to be current smokers (1.3% vs. 24.7%) and more likely to be former smokers (59.7% vs. 26.0%) than standard academic service patients (p < 0.01). Patients presenting with incarcerated hernias (5.2% vs. 9.1%), recurrent (10.4% vs. 5.2%) and bilateral hernias (19.5% vs. 10.4%) were similar between the Chief's service and standard academic services, respectively (all p > 0.05). Operative times were longer for the Chief's service for open (123 min vs. 67, p < 0.01) and laparoscopic (112 min vs. 79, p = 0.02) repairs. Recurrence rates (6.5% vs. 3.9%, p = 0.47) and complications including infection, seroma or hematoma requiring evacuation and need for reoperation were similarly low (p > 0.05) between the Chief's and standard academic services, respectively. Despite low complication rates, Chief's service patients were more likely to present to the ED post-op (14.3% vs. 1.3%; p = 0.001), but readmission rates were similarly low (2.6% vs. 0%, p = 0.09). Providing general surgery chief residents with a supervised opportunity to direct, plan and provide surgical care in clinic and the operating room, as a transition to independent practice following graduation, is safe for patients presenting with inguinal hernias. Concerns about patient safety should not be a barrier to maximizing entrustment for the evaluation and operative management of select core general surgery diagnoses and operations.


The ZDHHC8 gene did not associate with bipolar disorder or schizophrenia.
The zinc finger and DHHC domain-containing protein 8 (ZDHHC8) gene is located on chromosome 22q11, which several genome scans have provided repeated evidence for a significant linkage with bipolar disorder (BPD) and schizophrenia. A recent study revealed that a single nucleotide polymorphism (SNP), rs175174, which has potential effects on splicing, in intron 4 of the ZDHHC8 gene is associated with susceptibility to patients with schizophrenia in US and South Africa. We examined three SNPs of the ZDHHC8 gene, including rs175174, by case-control association in Japanese patients with BPD (N=172) and controls (N=298) or patients with schizophrenia (N=407) and controls (N=497). No significant association with BPD or schizophrenia was observed. After stratification by subcategories, bipolar I and II of BPD, and paranoid and disorganized types of schizophrenia, no significant association was found, nor was a significant association with either disorder found after dividing by gender. These data suggest that the ZDHHC8 gene may not be associated with susceptibility to BPD or schizophrenia, at least in a Japanese population.


NMR studies of backbone-alkylated DNA: duplex stability, absolute stereochemistry, and chemical shift anomalies of prototypal isopropyl phosphotriester modified octanucleotides, (Rp,Rp)- and (Sp,Sp)-(d-[GGA(iPr)ATTCC])2 and -(d-[GGAA(iPr)TTCC])2.
The DNA octamer (d-[GGAATTCC])2 and four alkylated analogues, (Rp)-(d-[GGA(iPr)ATTCC])2, (Sp)-(d-[GGA(iPr)ATTCC])2, (Rp)-(d-[GGAA(iPr)TTCC])2, and (Sp)-(d-[GGAA(iPr)TTCC])2 have been examined using 1H and 31PNMR spectroscopies. Duplex stability, as monitored by both NMR and optical measurements, is shown to be a function of both site and stereochemistry of the phosphotriester moiety. Chemical shift changes relative to the native octamer indicate that there are long-range perturbations in the isopropylated molecules. 1HNMR is shown to be a general means by which stereochemistry at phosphorous can be determined.


Local cerebral glucose utilization in epileptic seizures of the mutant El mouse.
The neural pathway and the focus of the epileptic seizure of mutant El mice were studied by the [14C]2-deoxyglucose technique. In the mice with full tonic-clonic seizure, the entire neocortex and hippocampus showed a remarkably increased metabolic rate. By contrast, a lower metabolic rate was evident in the thalamic nuclei, central gray, locus coeruleus and some interstitial nuclei. The epileptic focus in El mice presumably exists in the hippocampus.


Identification of potential salivary biomarkers for Sjögren's syndrome with an untargeted metabolomic approach.
Despite the rise of metabolomics over the past years, and particularly salivary metabolomics, little research on Sjögren's syndrome (SS) biomarkers has focused on the salivary metabolome. This study aims to identify metabolites that could be used as biomarkers for SS. Using the software called XCMS online, the salivary metabolic profiles obtained with liquid chromatography coupled to high-resolution mass spectrometry for 18 female SS patients were compared to those obtained for 22 age-matched female healthy controls. A total of 91 metabolites showed differential expression in SS patients. A putative identification was proposed with the use of a database for 37 of these metabolites and, of these, 16 identifications were confirmed. Given the identified metabolites, some important metabolic pathways, such as amino acid metabolism, purine metabolism, or even the citric acid cycle seem to be affected. Through the analyses of the ROC (receiver operating characteristic) curves, three metabolites, namely alanine, isovaleric acid, and succinic acid, showed both good sensitivity (respectively 1.000, 1.000, and 0.750) and specificity (respectively 0.692, 0.615, and 0.692) for identifying SS and could then be interesting biomarkers for a potential salivary diagnosis test.


Draft Genome Sequence of Cronobacter sakazakii Cr268, Isolated from Infant Powder Formula.
Cronobacter sakazakii is an emerging pathogen that causes meningitis, bacteremia, sepsis, and necrotizing enterocolitis in premature infants. Strain Cr268 was isolated from imported powdered infant formula in 2009 during routine microbial examination according to ISO-22964 ("Microbiology of the food chain-horizontal method for the detection of Cronobacter spp."). Isolate Cr268 was confirmed to be C. sakazakii by matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) and standard biochemical analysis. Here, we announce its genome, which represents a new member in the C. sakazakii group.


On the mechanism of the insulin-glucose interactions.
Analysis of the course of D-glucose binding to insulin has shown that the mechanism of glucose-insulin interaction is a cooperative process. Binding of D-glucose molecules to insulin is facilitated by the dissociation of insulin aggregates caused by insulin-glucose interaction. Thus, insulin behaves as a system with strong positive cooperativity. The results have been treated in accordance with theories for interactions coupled to association equilibria. The data obtained support the idea that insulin monomers are the active species responsible for insulin action.


Geoenvironmental characterisation of legacy mine wastes from Tasmania - Environmental risks and opportunities for remediation and value recovery.
A detailed characterisation of potential environmental risks is required to implement adequate mine waste management strategies at abandoned mine sites. This study assessed the long-term potential of six legacy mine wastes from Tasmania to generate acid and metalliferous drainage (AMD). Mineralogical analyses by X-ray diffraction (XRD) and mineral liberation analysis (MLA) revealed the mine wastes were oxidised onsite and contained up to 69% of pyrite, chalcopyrite, sphalerite, and galena. Oxidation of the sulfides under laboratory static and kinetic leach tests generated leachates with pH 1.9-6.5, suggesting long-term acid-forming potentials. The leachates contained some potentially toxic elements (PTE)s including Al, As, Cd, Cr, Cu, Pb, and Zn in concentrations exceeding the Australian freshwater guidelines by up to 105 times. The indices of contamination (IC) and toxicity factors (TF)s of the PTEs ranked between very low and very high relative to soils, sediments, and freshwater guidelines. The outcomes of this study highlighted the need for AMD remediation at the historical mine sites. Passive addition of alkalinity is the most practical remediation measure for these sites. They may also be opportunities for the recovery of quartz, pyrite, Cu, Pb, Mn, and Zn from some of the mine wastes.


Methodology and implementation of a tunable deep-ultraviolet laser source for photoemission electron microscopy.
Photoemission electron microscopy (PEEM) is a unique and powerful tool for studying the electronic properties of materials and surfaces. However, it requires intense and well-controlled light sources with photon energies ranging from the UV to soft X-rays for achieving high spatial resolution and image contrast. Traditionally, many PEEMs were installed at synchrotron light sources to access intense and tunable soft X-rays. More recently, the maturation of solid-state lasers has opened a new avenue for laboratory-based PEEMs using laser-based UV light at lower photon energies. Here, we report on the characteristics of a laser-based UV light source that was recently integrated with a PEEM instrument. The system consists of a high repetition rate, tunable wavelength laser coupled to a harmonics generation module, which generates deep-UV radiation from 192 nm to 210 nm. We comment on the spectral characteristics and overall laser system stability, as well as on the effects of space charge within the PEEM microscope at high UV laser fluxes. Further, we show an example of imaging on gallium nitride, where the higher UV photon energy and flux of the laser provides considerably improved image quality, compared to a conventional light source. These results demonstrate the capabilities of laser-based UV light sources for advancing laboratory-based PEEMs.


Medical assessment of elderly persons prior to a move to residential care: a review of seven years' experience in Edinburgh.
Assessment prior to a move to residential care has been carried out by the Departments of Geriatric Medicine in the Lothian Region for many years. Results have been reviewed over 7 years in one Department; 688 people were assessed; 7% were placed in alternative accommodation as a result of the assessment and a further 15% were offered specialist advice. The workload was 50 assessments per 10,000 population over 65 years per year. Of these, 58% were already known to the geriatrician and 23% were seen as part of the normal work of the department. It was concluded that the benefits of assessment make the extra work involved well worth while.


The association of pre-transplant atrial fibrillation with in-hospital outcomes in patients undergoing orthotopic liver transplantation: A propensity score matching analysis.
In this study, we sought to evaluate the prevalence and association of pre-transplant atrial fibrillation (AF) on 30-day postoperative outcomes in patients undergoing orthotopic liver transplant (OLT). The National Inpatient Sample Database was queried from 2011 to 2017 for relevant ICD-9 and ICD-10 procedural and diagnostic codes. Baseline characteristics and in-hospital outcomes were compared in patients who underwent OLT with AF and those without. Among 45,357 patients who underwent OLT, women made up 35.8% of the overall population. The prevalence of AF before transplant was 2932 (6.5%) with a trend toward increasing prevalence, with an average annual change rate of 4.19%. Applying propensity score matching to control for potential confounding factors, there was no association between pre-transplant AF and in-hospital mortality in patients undergoing OLT, however there was a higher incidence of perioperative complications including: acute kidney injury, ventricular tachycardia, major bleeding, blood product transfusion, and septic shock. In patients undergoing OLT, pre-transplant AF is increasing in prevalence and appears to be associated with similar in-hospital mortality but worse perioperative outcomes. Greater emphasis should be placed on AF in the preoperative cardiovascular risk stratification of patients undergoing OLT.


Insight into the molecular dynamics of guest cations confined in deformable azido coordination frameworks.
The molecular dynamics of encapsulated cations within perovskite-like coordination polymers [(CH3)3NH][M(N3)3] (M = Mn, Cd) are investigated, which are well controlled by the confined space of a deformable azido framework. The Mn-based compound provides a rare example that features an unvaried/varied rotational energy barrier during its two different structural phase transitions.


Additional value of thallium-201 SPECT to a conventional exercise test for the identification of severe coronary lesions after an episode of unstable coronary artery disease.
The additional value of thallium-201 SPECT to a conventional exercise test for the identification of patients with severe coronary lesions was evaluated in 170 men, one month after an episode of unstable coronary artery disease. Severe coronary lesions at coronary angiography--defined as three vessel disease, left main stenosis or proximal left anterior descending artery stenosis as part of two vessel disease--were observed in 45.9%. In the SPECT image, the left ventricular myocardium was divided into nine segments and each segment was classified as either normal (= 0), reduced uptake (= 1) or uptake defect (= 2). The sum of gradings in all segments post-exercise was denoted "SPECT score". The patients were divided into nine different groups regarding ST-depression during exercise (no ST-depression, ST-depression in 1-2 leads or > or = 3 leads) and "SPECT score" (no SPECT score, 1-3 scores or > or = 4 scores). Severe coronary lesions were, in 68% identified by SPECT score > or = 4 and in 65% by ST-depression in > or = 1 lead at exercise test. The specificity for identification of severe coronary lesions was, for both tests, 65%. SPECT score > or = 4 and/or ST-depression in > or = 3 leads identified 82% of the patients with severe coronary lesions with a specificity of 63%. Furthermore, SPECT score > or = 3 identified more patients with isolated proximal left anterior descending artery stenosis than ST-depression alone at exercise test.


Ten-year risk prediction in French men using the Framingham coronary score: results from the national SU.VI.MAX cohort.
To evaluate the ability of the Framingham risk function to predict the 10-year coronary heart disease (CHD) risk in French men. 3440 men, aged 45 to 60 years, free of CHD at baseline, were selected from the SU.VI.MAX cohort. The expected number of event, obtained from applying the Framingham risk score to the baseline SU.VI.MAX biological and clinical data of 1994/1996, were compared to the actual risks observed in the cohort. The accuracy of the Framingham risk function was assessed using the area under the receiver operating characteristic (ROC) curve. The overall Framingham risk function predicted twice as many CHD events than observed. The area under the ROC curve for Framingham risk score was 74%. The Framingham risk function may discriminate between high risk from low risk subjects, but it is not valid for estimating absolute 10-year CHD risk in this French population.


Hospital outbreak of the severe acute respiratory coronavirus virus 2 (SARS-CoV-2) delta variant in partially and fully vaccinated patients and healthcare workers in Toronto, Canada.
The severe acute respiratory coronavirus virus 2 (SARS-CoV-2) delta variant is highly transmissible, and current vaccines may have reduced effectiveness in preventing symptomatic infection. Using epidemiological and genomic analyses, we investigated an outbreak of the variant in an acute-care setting among partially and fully vaccinated individuals. Effective outbreak control was achieved using standard measures.


Flow injection system for potentiometric determination of alkaline phosphatase inhibitors.
A simple flow injection system for potentiometric detection of alkaline phosphatase (ALP) activity has been developed and adapted for determination of selected inhibitors of this enzyme. In this system monofluorophosphate (MFP) has been applied as a specific ALP substrate. The use of this substrate enables application of fluoride ion selective electrode (FISE) as a detector of the product of the enzyme catalyzed reaction. Moreover, chemical stability and low cost of MFP enables the use of the substrate as a component of the carrier. This way, fluoride ions contained in this substrate define and stabilize baseline signal generated by the detector. Effects from several potential ALP inhibitors and interfering species were studied and discussed. The system allows inhibitive detection of beryllium and vanadate ions at ppb levels with relatively high selectivity, short time of analysis and high throughput of the system (near 8 samples h(-1)).


Factors that support change in the delivery of midwifery led care in hospital settings. A review of current literature.
In hospital units, the network of interdependent relationships between midwives and doctors has positioned midwives within hierarchical relationships of power. Others argue that the physical layout of hospital wards created by biomedicine makes it difficult for midwives to provide midwifery led care. The aim of this review is to identify factors that support change in the delivery of the midwifery led care in hospital settings. A narrative review was chosen as this method allows for greater flexibility in the selection of studies and can lead to the inclusion of a wider range of literature. Eight high quality papers from the UK, Sweden, Canada and Australia were selected for review. Papers focused on improving the delivery of midwife led care in hospital midwifery units, labour and postnatal wards. Key themes were identified as supporting change in the delivery of midwifery led care were ownership of change, capability to change and transformational leadership. The findings demonstrate the importance of social support and clinical leadership in bringing about subtle changes in hospital based midwifery led care. Ultimately improved understanding of the factors that support the delivery of the midwifery led care in hospital settings may improve women's choice and highlight the role of the midwife as the practitioner of normal childbirth.


Changes in cardiovascular adrenoceptor response in rats subsequent to myocardial infarction.
Since sympatho-adrenal activity was greatest on the second day after experimental myocardial infarction in the rat, we investigated the responsiveness of cardiovascular adrenoceptors in pithed rats at this time and also determined the number of beta-adrenoceptors in the myocardium of the rats. In addition, the sympathetic outflow was measured, as a presynaptic parameter for estimating sympathetic nervous activity. The number of beta-adrenoceptor binding sites and the frequency responses of the heart were unchanged by myocardial infarction on the second day. There was also no difference from control animals with respect to sympathetic outflow. However, the rise in diastolic blood pressure, caused by electrical stimulation of the sympathetic nervous system, was far more pronounced in animals with infarction than in controls. In contrast, rats with myocardial infarction exhibited an attenuated response of diastolic blood pressure to infused noradrenaline. The observed effects can possibly be explained by changes of alpha-adrenoceptors, or perhaps by an enhanced degradation of catecholamines in the endothelium.


Anchor and Krackow-"8" Suture for the Fixation of Distal Pole Fractures of the Patella: Comparison to Kirschner Wire.
The study aim was to evaluate the clinical outcomes, functional outcomes, and postoperative complications of anchor and Krackow-"8" suture fixation (AS) and K-wire fixation in patients with distal pole patellar fractures. Twenty-eight patients with distal pole patella fractures between January 2011 and December 2014 were reviewed retrospectively. The anchor and Krackow-"8" suture fixation (AS group) was applied in 10 patients and 18 patients underwent K-wire fixation (K-wire group). The average age of patients was 46.000 ± 19.476 years in the AS group and 47.556 ± 15.704 years in the K-wire group, with comparable demographic characteristics. All patients underwent regular follow-up the operative data and postoperative functional and clinical outcomes were recorded. Complications were recorded by clinical and radiographic assessment. Bostman patellar fracture functional score was used to evaluate knee function after patellar fracture. A total of 28 eligible patients were included in this study. The mean follow-up was similar for the AS and the K-wire groups (P > 0.05). The incision length of AS group was significantly smaller than that of K-wire group (P < 0.05). The incision length of AS group was significantly smaller than that of K-wire group (P < 0.05). The final follow-up on the range of motion of the knee: the average extension lag was similar in two groups (P > 0.05); flexion and flexion-extension angle was slightly better in the AS group than in the K-wire group. The Bostman patella fracture functional score of AS group were better than K-wire group at 3 and 6 months after operation. Four kinds of postoperative complications in two groups, one patient (10%) in the AS group and two patients (11.1%) in the K-wire group had infections. Two (11.1%) cases of nonunion in group K and three patients (16.7%) required re-operation: one due to infection and two due to early implant failure. In the AS group, all distal pole fractures of the patella showed bony union, without loosening, falling, pulling out and nonunion of the fractures 6 months after operation. Anchor and Krackow-"8" suture fixation is an easily executed surgical procedure that can significantly reduce incision length and achieve better surgical outcomes than traditional procedures with regard to postoperative complications, knee function and without requiring a second operation. This technique is an effective operation method for the treatment of inferior patellar pole fractures.


Fractal analysis of the laminar organization of spinal cord neurons.
Images of Golgi impregnated neurons from different laminae of the human and rat dorsal horns were subjected to a quantitative analysis to support the Rexed's laminar scheme in mammals. Four methods of fractal analysis were performed in the proceedings: box-counting, mass-radius, cumulative intersection, and vectorized intersection. The results show that the box-counting method is more precise than the other fractal methods performed, and offers support for the conclusion that fractal analysis can successfully discriminate the neuron populations among different laminae. The analysis supports the concept of Rexed's cytoarchitectonic lamination of the dorsal horn.


Cisapride in the management of chronic functional dyspepsia: a multicenter, double-blind, placebo-controlled study.
The effects of cisapride, a nondopaminolytic motility-enhancing agent, were studied in 56 patients with chronic functional dyspepsia; all had symptoms suggestive of delayed gastric emptying. The patients received 4 mg or 8 mg of cisapride or placebo orally three times daily for two successive three-week periods according to a randomized, double-blind, crossover study design. Although there was a high placebo response (55% showed good or excellent results), the global response to treatment was significantly (P = 0.024) in favor of cisapride (75% had good or excellent results). The drug was particularly superior to placebo (P = 0.03) in the improvement of a cluster of symptoms typical of postprandial discomfort, including early satiety and nausea. Side effects were minimal.


Age-dependent accumulation of genomic aberrations and deregulation of cell cycle and telomerase genes in metastatic neuroblastoma.
About 50% of children with neuroblastoma (NB) show a metastatic disease and have a poor prognosis. However, disease progression is greatly variable and depends on patients' age and MYCN oncogene amplification. To investigate the role of patients' age in tumor aggressiveness, we performed array-CGH and gene expression profiles of three groups (G) of metastatic NBs: G1, stage 4S patients and MYCN single copy (MYCN-) tumors; G2, stage 4 patients, ≤ 18 months of age, MYCN- tumors and favorable outcome and G3, Stage 4 patients, ≥ 19 months with unfavorable outcome. G1 was characterized by numerical aberrations prevalently; on the contrary, all G3 tumors had structural rearrangements, whereas G2 showed an intermediate pattern. The average of numerical alterations decreased significantly from G1 to G2 to G3 (p < 0.01). Contrarily, the number of structural aberrations increased from G1 to G2 to G3 (p < 2.35 E-05). Noteworthy, G3/MYCN- NBs were characterized by several complex intrachromosome rearrangements. Expression analysis of the three groups showed significant differences in genes of Rho and Ras signaling pathways, development and adhesion, cell cycle regulation and telomerase activity. Accumulation of structural alterations increased with patients' age and was associated with a more aggressive disease. Abnormal expression of genes involved in cell cycle and telomerase in G3 may be responsible for the genomic instability in this cohort of patients. The higher DNA instability observed in G3/MYCN- NBs than in MYCN-amplified G3 may also explain why patients ≥ 19 months have a poor outcome independently by MYCN status.


Interpreting an ECG. Atrial premature complex.
When APCs are symptomatic or are a potential trigger for supraventricular tachycardia or atrial fibrillation, suppressive therapy with beta-blocking drugs or type I antiarrhythmic agents is indicated. If APCs are infrequent and produce no symptoms, attention to possible provocative factors--excess tobacco or caffeine, or drugs (eg, sympathomimetic amines, monoamine oxidase inhibitors, tricyclic antidepressants)--is all that is required.


Glycation modulates superoxide dismutase 1 aggregation and toxicity in models of sporadic amyotrophic lateral sclerosis.
Different SOD1 proteoforms are implicated## in both familial and sporadic cases of Amyotrophic Lateral Sclerosis (ALS), an aging-associated disease that affects motor neurons. SOD1 is crucial to neuronal metabolism and health, regulating the oxidative stress response and the shift between oxidative-fermentative metabolism, which is important for astrocyte-neuron metabolic cooperation. Neurons have a limited capacity to metabolize methylglyoxal (MGO), a potentially toxic side product of glycolysis. MGO is highly reactive and can readily posttranslationally modify proteins, in a reaction known as glycation, impacting their normal biology. Here, we aimed to investigate the effect of glycation on the aggregation and toxicity of human SOD1WT (hSOD1WT). Cells with deficiency in MGO metabolism showed increased levels of hSOD1WT inclusions, displaying also reduced hSOD1WT activity and viability. Strikingly, we also found that the presence of hSOD1WT in stress granules increased upon MGO treatment. The treatment of recombinant hSOD1WT with MGO resulted in the formation of SDS-stable oligomers, specially trimers, and thioflavin-T positive aggregates, which can promote cell toxicity and TDP-43 pathology. Together, our results suggest that glycation may play a still underappreciated role on hSOD1WT and TDP-43 pathologies in sporadic ALS, which could open novel perspectives for therapeutic intervention.


Discomalleolar and anterior malleolar ligaments: possible causes of middle ear damage during temporomandibular joint surgery.
Damage to structures within the middle ear during surgical manipulation of the temporomandibular joint (TMJ) has been reported. Two structures are proposed as possible intermediaries in this trauma: the discomalleolar ligament (DML), which passes from the malleus to the medial retrodiscal tissue of the TMJ, and the anterior malleolar ligament (AML), which connects the malleus with the lingula of the mandible via the sphenomandibular ligament (SML). It has been hypothesized that when tension is applied to the DML and/or AML, the resulting movement of the malleus could cause damage to the tympanic membrane and associated structures. The objective of this study was to determine whether tension applied to the DML and/or the AML could cause movement of the malleus. With the use of a superior medial approach through the middle cranial fossa, the ligaments connecting the malleus with the mandible were examined in 52 adult/human cadaveric half-heads. Tension applied directly to the SML resulted in movement of the malleus in three specimens. Similar tension applied to the DML did not cause movement of the malleus. Histologic evidence showed a continuity of fibers between the SML and AML. When the mandibular condyle was distracted inferiorly, tension was demonstrated in the SML. The results indicate that the AML via the SML has the potential to cause middle ear damage and is more likely to do so than the DML.


Drought relations of shrub species: assessment of the mechanisms of drought resistance.
Relatively static factors such as depth of rooting and cuticular conductance and relatively dynamic factors such as stomatol control and changes in the components of water potential were used to assess the drought resistance characteristics of six deciduous shrub species. Predawn water potential during a prolonged drought averaged-2.13 and-3.51 MPa in species known to have deep and shallow patterns of rooting, respectively. It is thus surprising that the osmotic potential at the turgor loss point averaged only-3.01 MPa in the shallow rooted group. The water potential at which irreversible cell damage occurred was the same in both groups (-4.9 MPa), and minimum values observed in the field never dropped below-4.0 MPa. There was, however, a pronounced difference between the two groups with regard to stomatal behavior. This allowed us to characterize the deep-rooted species as avoiders of stress which would cause prolonged stomatal closure whereas the shallow-rooted species had to tolerate prolonged periods of closed stomata.


Muscarinic agonists inhibit the ATP-dependent potassium current and suppress the ventricle-Purkinje action potential dispersion.
Activation of the parasympathetic nervous system has been reported to have an antiarrhythmic role during ischemia-reperfusion injury by decreasing the arrhythmia triggers. Furthermore, it was reported that the parasympathetic neurotransmitter acetylcholine is able to modulate the ATP-dependent potassium current (I K-ATP), a crucial current activated during hypoxia. However, the possible significance of this current modulation in the antiarrhythmic mechanism is not fully clarified. Action potentials were measured using the conventional microelectrode technique from canine left ventricular papillary muscle and free-running Purkinje fibers, under normal and hypoxic conditions. Ionic currents were measured using the whole-cell configuration of the patch-clamp method. Acetylcholine at 5 μmol/L did not influence the action potential duration (APD) either in Purkinje fibers or in papillary muscle preparations. In contrast, it significantly lengthened the APD and suppressed the Purkinje-ventricle APD dispersion when it was administered after 5 μmol/L pinacidil application. Carbachol at 3 μmol/L reduced the pinacidil-activated I K-ATP under voltage-clamp conditions. Acetylcholine lengthened the ventricular action potential under simulated ischemia condition. In this study, we found that acetylcholine inhibits the I K-ATP and thus suppresses the ventricle-Purkinje APD dispersion. We conclude that parasympathetic tone may reduce the arrhythmogenic substrate exerting a complex antiarrhythmic mechanism during hypoxic conditions.


Pelvic pain: an undescribed paroxysmal manifestation of multiple sclerosis.
We report a patient with pelvic pain as a paroxysmal manifestation of multiple sclerosis (MS). This phenomenon has not been described previously; it can lead to diagnostic difficulties. Like other paroxysmal manifestations, it showed a good response to carbamazepine. The literature on paroxysmal manifestations of MS and some possible pathogenic mechanisms are reviewed briefly.


Salvage of pilon fracture nonunion and infection with circular tensioned wire fixation.
Nonunion, malunion, and infection are complications encountered when treating fractures of the distal tibia extending into the joint surface. There is rank order of severity of those complications extending from a varus collapse of the medial column of the distal tibia with a reduced joint surface to an infected nonunion with destruction of the joint surface, segmental bone loss, and damaged soft tissue envelope. Malunion and malposition of nonunion of the distal tibia have a combination of angular deformity, translation, rotational malalignment, and shortening. These deformities require correction in the reconstruction and there are multiple technique pathways to achieving a successful reconstruction.


Work-related musculoskeletal disorders among dental staff in Armed Force Hospital in Dhahran, Saudi Arabia.
Work related musculoskeletal disorders' (WMSDs) are the most important public health challenge among dental staff. The objective of study was to ascertain the prevalence and risk factors for work related musculoskeletal disorder among dental staff in Dhahran, Saudi Arabia. It is a cross sectional study and 130 dental staff with at least 1 year of working experience were random selected from Armed Forced Hospital. The self-administered validated and structured Standardized Nordic questionnaire was used. Logistic regression analysis was done to determine the association of risk factors with WMSD. the results of the present study revealed that there was a high incidence of MSDs in neck, shoulder, and lower back pain among dental personnel (72.6%). The common risk factors which contributed to WMSD were more than 5 year of experience (AOR 1.19(1.03-2.82)), Saudi nationality (AOR 4.88 (1.27 - 18.72)), working more than 12 hours (AOR 3.115 (1.258 7.578)) and resident doctors (AOR 1.14 (1.02 - 1.94)). The study conclude work related MSD were common with high rate of incidence among dental staff . There is need to make a policy which will reduce the burden of WMSD among dental staff.


Transfer status in geriatric hip fracture surgery - An independent risk factor associated with 30-day mortality, re-operations and complications.
A significant proportion of patients undergoing hip fracture surgery are transferred from other locations. With no current orthopedic literature present, we sought to study the impact of transfer location on 30-day outcomes following geriatric hip fracture surgery. The 2015-2016 ACS-NSQIP database was queried using CPT codes to retrieve records of geriatric patients undergoing hip fracture surgery (total hip arthroplasty/THA, hemiarthroplasty/HA and open reduction internal fixation/ORIF). Transfer status was defined into four groups - 1) No transfer (admitted from home), 2) From acute care hospital, 3) From nursing home/chronic care facility and 4) From outside emergency department (ED). Patients with missing data were excluded. A total of 31,218 patients were included in the final cohort. Out of 31,218 patients - 23,659 (75.8%) were admitted from home, 1574 (5.0%) from acute care hospitals, 3299 (10.6%) from nursing home/chronic care facilities and 2686 (8.6%) from outside EDs. Following adjusted analysis, transfer from nursing home vs. home was associated with higher odds of 30-day mortality (OR 1.57 [95% 1.36-1.80]; p < 0.001), 30-day re-operations (OR 1.36 [95% CI 1.10-1.68]; p = 0.005), septic shock (OR 1.58 [95% CI 1.07-2.32]; p = 0.021), sepsis (OR 1.45 [95% CI 1.05-1.99]; p = 0.023) and urinary tract infection (OR 1.21 [95% CI 1.02-1.42]; p = 0.025). Additionally, transfer from outside ED vs. home was also associated with higher odds of 30-day mortality (OR 1.26 [95% CI 1.06-1.50]; p = 0.010).Transfer from any location (acute care hospital, nursing home and outside ED) was significantly associated with higher odds of non-home discharge (p < 0.001). Transfer status is an important risk factor associated with 30-day mortality and morbidity in geriatric patients undergoing hip fracture surgery. The findings stress the need for recognition of these patients as being a high-risk group to allow enhanced medical optimization in an attempt to minimize the risk of poor outcomes.


Intra- thecal antitetanus serum in the management of tetanus neonatorum.
Eleven neonates have treated with intra-thecal antitetanus serum in addition to other standard measures. Five survived. The results were judged promising.


Septic, CD-30 positive febrile ulceronecrotic pityriasis lichenoides et varioliformis acuta.
We report life-threatening febrile ulceronecrotic pityriasis lichenoides et varioliformis acuta in an 8-year-old girl. Hemorrhagic-crusted papules and plaques covered over 90% of the patient's body, leaving her susceptible to Pseudomonas aeruginosa and Staphylococcus epidermidis bacteremia as well as Candida parapsilosis fungemia. Sepsis delayed definitive treatment of the underlying cutaneous disease for 2 weeks. Combined therapy with methotrexate and cyclosporin caused remission of the process. Although immunohistochemistry revealed CD-30 positive cells, suggesting the diagnosis of lymphomatoid papulosis, the histopathology was most compatible with pityriasis lichenoides et varioliformis acuta. A partial loss of CD2 and CD5 in the predominant CD3 T-cell lymphocytes suggested a clonal proliferation. Elevated soluble interleukin-2 receptor levels reflected marked T-cell activation, and the downward trend of the levels during treatment coincided with clinical regression of this inflammatory dermatosis.


Identification of the dietary lectin, wheat germ agglutinin, in human intestinal contents.
Plant lectins are known to have potent biological actions of normal and malignant cells. High concentrations of these lectins are present in many types of high residue diets. The specific binding of wheat germ agglutinin, a dietary plant lectin, to N-acetylglucosamine was used as the basis for purification of this lectin by biospecific chitin affinity chromatography. Subsequently, methods were developed for the extraction, purification, and identification of wheat germ agglutinin from fecal samples. Biologically intact wheat germ agglutinin was detected in ileostomy effluent and fecal collections from human subjects consuming a diet containing wheat germ. These studies demonstrate that wheat germ agglutinin can traverse the human small intestine intact. It is feasible that orally ingested wheat germ agglutinin and other plant lectins which interact with a wide variety of cell membranes may alter intestinal epithelial or bacterial cell function in the human bowel.


Aggressive angiomyxoma with gastrointestinal communication: a case report.
We report the imaging findings of an abdominal aggressive angiomyxoma, which communicated with the gastrointestinal tract. The literature on this rare tumor is reviewed.


Retinoic acid dampens LPS-induced NF-kappaB activity: results from human monoblasts and in vivo imaging of NF-kappaB reporter mice.
Bacterial lipopolysaccharide (LPS) is a major inducer of systemic inflammatory reactions and oxidative stress in response to microbial infections and may cause sepsis. In the present study, we demonstrate that retinoic acid inhibits LPS-induced activation in transgenic reporter mice and human monoblasts through inhibition of nuclear factor kappaB (NF-kappaB). By using noninvasive molecular imaging of NF-kappaB luciferase reporter mice, we showed that administration of retinoic acid repressed LPS-induced whole-body luminescence, demonstrating in vivo the dynamics of retinoic acid's ability to repress physiologic response to LPS. Retinoic acid also inhibited LPS-induced NF-kappaB activity in the human myeloblastic cell line U937. Retinoic-acid-receptor-selective agonists mimicked - while specific antagonists inhibited - the effects of retinoic acid, suggesting the involvement of nuclear retinoic acid receptors. Retinoic acid also repressed LPS-induced transcription of NF-kappaB target genes such as IL-6, MCP-1 and COX-2. The effect of retinoic acid was dependent on new protein synthesis, was obstructed by a deacetylase inhibitor and was partly eliminated by a signal transducer and activator of transcription-1 (STAT1)/methyltransferase inhibitor, indicating that retinoic acid induces a new protein, possibly STAT1, that is involved in inhibiting NF-kappaB. This provides more evidence for retinoic acid's anti-inflammatory potential, which may have clinical implications in terms of fighting microbial infections.


[The Mechanisms of Transgenerational Inheritance and Their Potential Contribution to Human Phenotypes].
As of today, classical genetics has already completed the majority of groundwork to describe the laws of inheritance, identify the causes of many human diseases, and dissect the mechanisms of transfer of genetic information from parents to offspring. However, recent studies indicate that inheritance of phenotypic traits may also occur through nongenetic factors, in particular, through epigenetic factors, that manifest their effects in a transgenerational fashion. This review discusses findings in the area of transgenerational inheritance that open a new era in modern genetics. We discuss the mechanisms of transgenerational inheritance, including DNA methylation, histone modifications, and noncoding RNA transfer, and give an overview of the approaches to detect transgenerational effects in humans.


A metabocentric view of cardiac remodeling.
Physiologic and pathologic stressors promote changes in metabolism that are associated with cardiac remodeling. Metabolic alterations in the heart are a summation of responses of several organs and organ systems, which transform the milieu of circulating substrates and stimuli and prompt cardiac adaptation or remodeling. Nevertheless, the mechanisms by which metabolism causes cardiac remodeling remain unclear. Difficulties in delineating metabolic mechanisms of tissue remodeling are in part due to technical issues as well as to the lack of conceptual clarity with regard to causal entailment of metabolic processes. This review discusses some metabolic mechanisms by which stressors such as exercise, pregnancy, and pressure overload promote metabolism-mediated cardiac remodeling. Adopting conceptual frameworks based in relational biology and delineating hierarchies of metabolic causation could lend new insight into how metabolism coordinates cardiac remodeling.


Increase in skin cancer screening during a community-based randomized intervention trial.
Survival from cutaneous melanoma is mainly dependent on the thickness of the lesion at diagnosis. Skin screening may increase detection of thin lesions and hence improve survival. Within a community-based randomized controlled trial of a population screening program for melanoma in Queensland, Australia, 9 communities were randomly assigned to the 3-year intervention and 9 communities to the control group. Skin screening prevalence was monitored by cross-sectional surveys at baseline, 1, 2 and 3 years into the intervention and 2 years later. At baseline, prevalence of whole-body clinical skin examination was similar in intervention and control communities. In intervention communities, the prevalence of whole-body skin examinations increased to 29.2%, an absolute difference of 18% from baseline, with a peak of 34.8% 2 years after baseline, and began to decline again at the end of the intervention period. The largest increases were seen in men and women > or =50 years. Uptake of screening did not differ according to melanoma risk factors; however, the decline in screening was less in participants who reported a number of melanoma risk factors. The prevalence of skin self-examination remained stable during the intervention program. No changes were observed in the control communities. These results indicate that the intervention program significantly increased the prevalence of whole-body clinical skin examinations in intervention communities. Once the intervention program ceased, and particularly after skin clinics ceased, levels of skin screening began to decline. The provision of specialized skin screening clinics may be needed to achieve sufficient screening rates should population based screening for skin cancer be considered.


Isoelectric focusing in polyacrylamide-agarose.
A procedure using a 2.5% acrylamide-0.5% agarose gel for slab or tube isoelectric focusing is described. This composite gel is durable and enables a rapid focusing of high-molecular-weight compounds.


Nuclear localization and signalling activity of phosphoinositidase C beta in Swiss 3T3 cells.
The hydrolysis of phosphatidylinositol 4,5-bisphosphate (PtdInsP2) is a widespread receptor-coupled signalling system at the plasma membrane of most eukaryotic cells. The existence of an entirely separate nuclear phosphoinositide signalling system is suggested from evidence that purified nuclei synthesize PtdInsP2 and phosphatidylinositol 4-phosphate (PtdInsP) in vitro and that a transient decrease in the mass of these lipids occurs when Swiss 3T3 cells are cultured in the presence of insulin-like growth factor-1 (IGF-1). These IGF-1-dependent changes in inositol lipids coincide with an increase in nuclear diacyglycerol and precede translocation to the nucleus and activation of protein kinase C (refs 5, 6). Circumstantial evidence that links these changes with mitosis comes from the isolation of a 3T3 clone that expresses the type-1 IGF receptor and binds IGF-1 peptide but does not respond mitogenically or show transient mass changes in nuclear inositol lipids. A key question is how IGF-1 initiates the rapid breakdown of PtdInsP and PtdInsP2 in the nucleus. Here we present evidence that nuclei of 3T3 cells contain the beta-isozyme of phosphoinositidase C, whereas the gamma-isozyme is confined to the cytoplasm and that IGF-1 treatment stimulates exclusively the activity of nuclear phosphoinositidase C.


Climate change and their impacts in the Balearic Islands: a guide for policy design in Mediterranean regions.
Understanding the local effects of global warming-derived impacts is important to island systems due to their fragile environmental conditions. This is especially true when it comes to Mediterranean insular regions as they are climate change (CC) hotspots where adaptation and mitigation policy design is an urgent matter. Looking at 2030 as a time horizon for climate action and focusing on the Balearic Islands, this paper reviews the physical changes projected for the coming decades as a result of CC and analyses their impacts on regional environmental, economic and social variables. Mitigation and adaptation measures are also proposed based on the identified priority impacts. The fact the Balearics are a top world holiday destination allows the analysis to serve as a guide to other Mediterranean islands with tourism-based economies facing similar CC scenarios. Results show the projected rise of temperature and sea level; the reduction of the average precipitation and increase in evapotranspiration, the droughts and the increase in ocean acidification and deoxygenation are the main threats faced by the Balearics, this putting their economy at risk due to the high tourism's vulnerability to CC. Mitigation and adaptation action on terrestrial and marine ecosystems, water resources, energy, infrastructure and urban planning, human health, economy, law and education is recommended. Sustainable mobility and waste managing are also viewed as important fields for mitigation action. Conclusions show that diversifying the current socioeconomic model is needed to increase the community and territory resilience. The online version contains supplementary material available at 10.1007/s10113-021-01810-1.


Complex Aortic Arch Atherosclerosis in Acute Ischemic Stroke Patients with Non-Valvular Atrial Fibrillation.
Aortic arch atherosclerosis, particularly complex aortic arch plaques (CAPs), is an important source of cerebral emboli. CAPs and atrial fibrillation (AF) often co-exist; however, the prevalence and risk of CAPs in acute ischemic stroke patients with AF is unclear. In patients with acute ischemic stroke with non-valvular AF admitted to Jichi Medical University Hospital during April 2016 to September 2019, we retrospectively evaluated the presence of CAPs on transesophageal echocardiography (TEE). CAPs were observed in 41 (38.7 %) of 106 patients with non-valvular AF. Older age, diabetes mellitus, chronic kidney disease, low high-density lipoprotein cholesterol (HDL-C) levels, higher levels of glycohemoglobin A1c (HbA1c), higher CHADS2 and CHA2DS2-VASc scores, and intracranial or carotid artery stenosis were more frequently observed in CAPs-positive than in CAPs-negative patients. In multivariable analyses, older age (odds ratio [OR]: 1.2 per year increase; 95% confidence interval [CI]: 1.07-1.24; P<0.0001), diabetes mellitus (OR: 4.7; 95%CI: 1.27-17.35; P<0.05), and low HDL-C (OR: 0.95 per 1 mg/dl increase; 95%CI: 0.92-0.99; P<0.01) were independent risk factors for CAPs. The prevalence of CAPs was age-dependent, and there was a significantly higher risk in patients aged either 75-84 years or >84 years than in those aged <65 (OR: 7.6; 95%CI: 1.50-38.62, and OR: 32.1; 95%CI: 5.14-200.11, respectively). Even in patients with ischemic stroke with non-valvular AF, concomitant CAPs should be considered in older individuals and those who have diabetes or low HDL-C.


Food selectivity versus prey availability: a study using the marine fish Pomatoschistus microps.
The food selection of the common goby, Pomatoschistus microps Krøyer, was studied in the field and in laboratory experiments on the Swedish west coast. The three most important prey organisms for P. microps in the study area were Corophium volutator, chironomid larvae and Nereis spp. Corophium was consumed more than any other prey, even when it was not the most abundant prey species in the bottom. One reason may be the higher activity of Corophium above the sediment surface, which may increase its visibility and consequently its vulnerability to visual predators. When P. microps was offered Corophium and chironomid larvae with similar exposure in laboratory experiments, it showed no preference for either of the prey items. It always took the closest mobile prey, regardless of species and size.


Comparative studies of ribulose-1,5-biphosphate carboxylase/oxygenase from Alcaligenes eutrophus H16 cells, in the active and CABP-inhibited forms.
RuBisCO (D-ribulose-1,5-biphosphate carboxylase/oxygenase; EC 188.8.131.52) has been isolated from the autotrophic hydrogen-oxidizing bacterium Alcaligenes eutrophus H16. Combining photon correlation and sedimentation analysis transport parameters of the enzyme were investigated in the active, (E.CO2.Mg2+) as a ternary complex, and inactive state, (E.CO2.Mg2+.CABP) as a quaternary complex, where RuBisCO is complexed with the transition state analogue CABP (2-C-carboxy-D-arabinitol-1,5-biphosphate). Within experimental error, no difference has been detected between the diffusion and sedimentation coefficients (D020,w = 2.72(+/- 0.07) x 10(-7) cm2 s-1, s020,w = 17.8(+/- 0.5)S) of active and CABP-complexed enzyme thus leading to the conclusion that the molecule, at least in solution, does not assume a different conformation when complexed with CABP.