Too hot to handle? Behavioural plasticity during incubation in a small, Australian passerine.
Global warming and intensifying extreme heat events may affect avian reproductive success and costs, particularly in hot, arid environments. It is unclear how breeding birds alter their behaviour in response to rapid climate change, and whether such plasticity will be sufficient to offset rising temperatures. We examine whether a small, open-cup nesting, passerine - the Jacky Winter Microeca fascinans - in semi-arid Australia, exhibits similar levels of behavioural plasticity when incubating under high temperatures as low, and how heat impacts upon parental effort, body mass change and reproductive success. At high temperatures, female effort increased. Females doubled nest attendance between 28 °C and 40 °C, switching from incubating to shading eggs at approx. 30 °C. Egg-shading females panted to avoid hyperthermia. Panting increased with temperature and sun exposure. Male breeding effort was linked to temperature extremes. In cold conditions, males provisioned their mates heavily, buffering females from additional energetic costs, and males suffered a loss of body mass. In extreme heat, males helped shade eggs (although they never incubated). The likelihood of male egg-shading increased with temperature, but level of contribution was positively related to sun exposure. Hatching success declined with air temperatures >35 °C. Egg mortality reached 100 at air temperatures >42.5 °C. Parents continued to attend unviable eggs (for up to two weeks), suggesting egg-loss from heat exposure is a recent phenomenon. Although pairs exhibited considerable behavioural plasticity - including positioning nests to maximize afternoon shade - this was insufficient to counter extreme temperatures. In 2019, one hot day (45 °C) effectively terminated reproduction two months early, and was associated with a 50% decrease in reproductive success. The increasing frequency, intensity and earlier arrival of extreme heat events is likely to pose a major threat to avifauna populations in hot, arid environments, due to increased parental costs, reduced reproductive success and direct mortality.


Recombinant activated Factor VII in major surgery and trauma patients: a response.
The review article by Wilson et al. (Expert Opin. Drug Saf., 2005) on recombinant activated Factor VII (rFVIIa) offers some valuable insights into the ongoing exploration of this agent in the management of uncontrolled bleeding--an area of high unmet clinical need. This editorial highlights that the chosen citation of Riou et al. (Shock, 2004), in reference to two parallel studies conducted in trauma patients with blunt and penetrating injury, was both a report of an early analysis of the data, and was only one of several abstracts on these studies published in 2004. The authors of this editorial believe that the inclusion of the other published abstracts in this series would have provided a more comprehensive and balanced overview of recombinant activated Factor VII.


Broad spectrum anthelmintic resistance of Haemonchus contortus in Northern NSW of Australia.
On a sheep farm in Northern New South Wales (NSW) of Australia a degree of anthelmintic resistance was suspected. With noticeable clinical signs of infection and sheep not responding to treatment, a faecal egg count reduction test was conducted to ascertain the broad spectrum of anthelmintic resistance at this farm. A number of classes of anthelmintics were assessed including organophosphate, macrocyclic lactone (ML) and in combination an ML, benzimidazole, levamisole and salicylanilide. In addition, the more recently registered classes of anthelmintics, monepantel (amino-acetonitrile derivative) and derquantel/abamectin combination (spiroindole+ML) were included. Ninety merino sheep naturally infected with a field strain of Haemonchus contortus were randomly allocated to 6 treatment groups (15 animals/group). Sheep were subsequently treated based on label recommendations and individual bodyweight. Faecal samples were collected post-treatment on Days 7, 14 and 21 to conduct faecal egg counts and group bulk larval cultures. Broad spectrum anthelmintic resistance was confirmed at this site with treatment efficacies ranging from 21.3% (monepantel) to 93.8% (derquantel/abamectin combination) against the H. contortus strain. Furthermore, resistance to the multi-combination anthelmintic containing 4 active ingredients was evident (52.5%). This broad spectrum of resistance highlights the need for integration of alternative sustainable methods in parasite control in order to slow development of resistance and increase the life time effectiveness of anthelmintics.


Current Advances in Multiple Myeloma: A Post International Myeloma Society (IMS 2022) Round Table Debate by the International Academy for Clinical Hematology (IACH).
This round table discussion organized by the International Academy for Clinical Hematology (IACH) was dedicated to the 19th annual meeting of the International Myeloma Society (IMS), which was held in Los Angeles between the 25th and 27th August 2022. After some key meetings of the discipline of the field of clinical hematology, the IACH organizes regular round table discussion in order to summarize the flow of information and get the opinion of a panel of experts and the key take-home messages. As part of this discussion, the panellists debated 6 key topics: disease monitoring, management of high-risk multiple myeloma (MM), induction for newly-diagnosed MM, management of relapsed MM, immune reconstitution, and vaccination and cellular therapy in MM.


Influence of osmotic stress on fermentative production of succinic acid by Actinobacillus succinogenes.
This study investigated the influence of osmotic stress on succinic acid production by Actinobacillus succinogenes NJ113. Both cell growth and succinic acid production were inhibited with the increase in osmotic stress of the medium. The use of three different osmoprotectants in the production of succinic acid was studied in order to decrease the inhibitory effects of osmotic stress during fermentation. Results indicated that proline offers optimal osmoprotection in the production of succinic acid by A. succinogenes NJ113. In tests of batch fermentation, the maximum cell concentration was observed to be 5.36 g DCW/L after the addition of 25 mmol/L proline to the fermentation medium. The cell concentration was 24% higher than that noted for the control. A total quantity of 56.2 g/L of succinic acid was produced, with a production rate of 1 g/L per hour, after 56 h of fermentation. The concentration and productivity of succinic acid was observed to be increased by 22.2% and 22%, respectively, as compared with the control. The specific activity levels of key enzymes in the metabolic network was noted to be higher following the addition of proline, particularly in the later stages of fermentation. This method of enhancing succinic acid production by the addition of an osmoprotectant may potentially provide an alternative approach for enhanced production of other organic acids.


Psychiatric morbidity in the relatives of patients with DSM-III schizophreniform disorder: comparisons with the relatives of schizophrenic and bipolar disorder patients.
Risks for psychiatric disorders (RDC) among first degree relatives of DSM-III schizophreniform, bipolar, and schizophrenic probands obtained from an epidemiologic sample using family history methods were examined. The relatives of the schizophreniform probands differed from the relatives of the schizophrenic and bipolar probands. The relatives of schizophreniform probands had significantly higher rates of affective illnesses (with the exception of bipolar illness) than the relatives of schizophrenic probands, and they had a significantly higher rate of psychotic affective disorders than the relatives of the bipolar probands.


Effects of selective D-1 and D-2 dopamine antagonists on development of methamphetamine-induced behavioral sensitization.
The present study examined effects of selective antagonists of D-1 and D-2 dopamine receptors on the development of behavioral sensitization produced by repeated methamphetamine (MAP) administration. Male Sprague-Dawley rats were divided into four groups. Each group received a daily injection of saline (control group), 4 mg/kg MAP (MAP group), 1 mg/kg YM-09151-2 plus 4 mg/kg MAP (YM + MAP group) or 0.5 mg/kg SCH 23390 plus 4 mg/kg MAP (SCH + MAP group) for 14 days. During daily injection for 14 days, the MAP group exhibited a progressive augmentation in locomotor and stereotyped behavior, whereas the progression of such behaviors in the YM + MAP and SCH + MAP group was completely prevented. After an abstinence period of 7 days, all groups received a challenge of 2 mg/kg MAP. The MAP challenge reproduced hyperlocomotion and intense stereotyped behavior only in the MAP group. However, neither the YM + MAP group nor the SCH + MAP group showed stereotypy. The manner in which both groups showed only hyperlocomotion was similar to that observed in the control group. These results indicate that both selective D-1 antagonists and selective D-2 antagonists not only reverse MAP-induced motor effects at each injection but also prevent the development of behavioral sensitization induced by repeated MAP administration.


Effects of propofol on cortico-cortical evoked potentials in the dorsal language white matter pathway.
In order to evaluate the clinical utility even under general anesthesia, the present study aimed to clarify the effect of anesthesia on the cortico-cortical evoked potentials (CCEPs). We analyzed 14 patients' data in monitoring the integrity of the dorsal language pathway by using CCEPs both under general anesthesia with propofol and remifentanil and awake condition, with the main aim of clarifying the effect of anesthesia on the distribution and waveform of CCEPs. The distribution of larger CCEP response sites, including the locus of the maximum CCEP response site, was marginally affected by anesthesia. With regard to similarity of waveforms, the mean waveform correlation coefficient indicated a strong agreement. CCEP N1 amplitude increased by an average of 25.8% from general anesthesia to waking, except three patients. CCEP N1 latencies had no correlation in changes between the two conditions. We demonstrated that the distribution of larger CCEP responses was marginally affected by anesthesia and that the CCEP N1 amplitude had tendency to increase from general anesthesia to the awake condition. The CCEP method provides the efficiency of intraoperative monitoring for dorsal language white matter pathway even under general anesthesia.


Recent developments in the social identity approach to the psychology of climate change.
We review recent literature on the social psychology of climate change, focusing on the application of social identity theory and self-categorization theory. These two theories, together forming the social identity approach, point to ways in which collective identities influence responses to climate change. Recent research demonstrates that collective identities influence attitudes, beliefs and behavior relevant to climate change, and they do this through processes such as group norms and social influence, collective efficacy, and collective emotions. The SIA suggests that, in general, people are motivated to protect the identity and status of their ingroups. Indeed, recent studies find that groups who are of higher status, and thus have more to gain from protecting the status quo, tend to be less concerned about addressing climate change than lower status groups, who are more likely to be harmed by climate change. However, individuals from both high and low status groups will be more likely to work towards pro-environmental social change when they perceive current social systems that perpetuate climate change as illegitimate and when they can imagine cognitive alternatives to the status quo, where humans have a more sustainable relationship with nature.


Macrophage-T cell interaction mediated by immunogenic and non-immunogenic forms of a monofunctional antigen.
As an approach to the elucidation of the essential steps in the immune pathway, the uptake and retention of immunogenic and non-immunogenic analogs of a monofunctional antigen by guinea pig macrophages and the efficiency of macrophages pulsed with the compounds to present antigen to sensitized T lymphocytes were compared. L-Tyrosine-azobenzene-p-arsonate (RAT) and its non-immunogenic analog, 4-hydroxyphenyl-n-propane-3-azobenzene-p-arsonate (RAN), react similarly with antiarsonate antibody, but RAN, unlike RAT, is unable to induce cellular immunity in guinea pigs. The uptake and retention patterns of the two compounds by macrophages differed in that, at a given time, more RAN than RAT was retained and detectable on cell surfaces by anti-arsonate antibody. Equivalent numbers of T lymphocytes from guinea pigs sensitized to RAT formed antigen-dependent clusters with macrophages pulsed with either RAT or RAN after 24 hr in culture, but not with macrophages pulsed with an azobenzenoid compound of unrelated specificity. On the other hand, T lymphocytes from guinea pigs immunized with RAN showed no significant capacity to bind to macrophages which had been pulsed with any of the compounds. The number of lymphocytes from RAT-sensitized animals which bound to RAT-pulsed macrophages remained relatively stable over a 48 hr period, whereas clusters of the same lymphocytes with RAN-pulsed macrophages dissocitated to background levels within that time. Early cluster formation mediated by RAN, as well as its ability to induce transient specific T cell unresponsiveness to RAT in vivo, indicate that T cells are capable of recognizing (binding) the non-immunogen. However, such early, and perhaps weak, interaction with RAN-pulsed macrophages did not induce DNA synthesis by T cells. Anti-Ia serum completely blocked cluster formation mediated by either RAT or RAN. Thus, the only significant distinction disclosed by these studies between the immunogenic and non-immunogenic compounds was the stability of macrophage-T cell interaction as determined by the persistence of antigen mediated cell clusters in culture, suggesting that this may be a factor in immunogenic discrimination.


The enigmatic role of Sir2 in aging.
In this issue of Cell, Longo and colleagues (Fabrizio et al., 2005) examine the role of Sir2, a histone deacetylase, in chronological aging in yeast by measuring the long-term survival of nondividing cells. In contrast to measurements of aging for mitotic cells, cell survival in the nonmitotic state is decreased by Sir2 activity under conditions that mimic calorie restriction.


Interpreting the influence of liquid temperature on cavitation collapse intensity through bubble dynamic analysis.
The violent collapse of inertial bubbles generates high temperature inside and emits strong impulsive pressure. Previous tests on sonoluminescence and cavitation erosion showed that the influence of liquid temperature on these two parameters is different. In this paper, we conducted a bubble dynamic analysis to explore the mechanism of the temperature effect and account for the above difference. The results show that the increase of vapor at higher liquid temperatures changes both the external compression pressure and the internal cushion and is responsible for the variation of bubble collapse intensity. The different trends of the collapsing temperature and emitted sound pressure are caused by the energy distribution during the bubble collapse. Moreover, a series of simulations are conducted to establish the distribution map of the optimum liquid temperature where the collapse intensity is maximized. The relationship between the collapse intensity and the radial dynamics of the bubble is discussed and the reliable indicator is identified. This study provides a clear picture of how the thermodynamic process changes cavitation aggressiveness and enriches the understanding of this complex thermal-hydrodynamic phenomenon.


Excessive exogenous cholesterol activating intestinal LXRα-ABCA1/G5/G8 signaling pathway can not reverse atherosclerosis in ApoE-/- mice.
The long-term excessive intake of exogenous cholesterol can lead to abnormally elevated blood lipid levels and induce cardiovascular and cerebrovascular diseases. However, the influence and relevance of exogenous cholesterol on plasma cholesterol components were still unclear, and the influence on intestinal lipid metabolism targets needs to be further explored. In vivo, the C57BL/6 + NF group and ApoE-/- + NF group mice were fed a normal specific pathogen-free (SPF) diet; the ApoE-/- + HF group mice were fed a high-cholesterol SPF diet. The plasma and jejunum tissue homogenate were obtained for non-targeted lipid metabolomics. The lipid droplets in tissues were observed by transmission electron microscope and oil red O staining. Jejunum tissue morphology was observed by HE staining. The kits were used to detect lipid content in plasma, tissues, intestinal contents, and cells. Western blot, RT-PCR, immunohistochemistry (IHC), and immunofluorescence (IF) were used to observe the key target of lipid metabolism. In vitro, the final concentration of cholesterol was 100 μmol/L in Caco-cells. Oil red O staining, western blot, RT-PCR and immunofluorescence (IF) were used to observe the changes of lipid metabolism. Finally, the influence of liver X receptor alpha (LXRα) on intestinal cholesterol metabolism was clarified by applying the LXRα inhibitor GSK2033 and siRNA targeting LXRα. The aortic arch and intestinal villi of the two groups of ApoE-/- mice showed apparent lesions and lipid accumulation, and there were significant changes in a variety of lipids in the plasma and jejunum. Additionally, jejunum LXRα was markedly activated. High cholesterol can significantly activate LXRα in Caco-2 cells. After LXRα was inhibited, the protein level of ATP-binding cassette transporter A1/G5/G8 (ABCA1/G5/G8) decreased, and the quantity and volume of intracellular lipids soared. In a high-cholesterol environment, the intestine promotes the excretion of cholesterol from the cell through the LXRα-ABCA1/G5/G8 pathway, reduces the intestinal intake of a variety of exogenous cholesterol, and reduces the risk of AS.


Metabolomics coupled with SystemsDock reveal the protective effect and the potential active components of Naozhenning granule against traumatic brain injury.
Naozhenning granule (NZN), a widely traditional Chinese medicine (TCM) prescription with a long history of clinical, which is mainly used in the treatment of concussion, cerebral post-traumatic syndrome, consists of Di Huang (Radix of Rehmannia glutinosa (Gaertn.) DC.), Dang Gui (Radix of Angelica sinensis (Oliv.) Diels), Chen Pi (Pericarpium of Citrus reticulata Blanco), Dan shen (Radix of Salvia Miltiorrhiza Bunge.), Di Long (Pheretima aspergillum (E. Perrier)), Mu Dan Pi (Cortex of Paeonia suffruticosa Andrews), Suan Zao Ren (Semen of Ziziphus jujuba Mill.), Chuan Xiong (Rhizoma of Ligusticum striatum DC.), Zhu Ru (Phyllostachys nigra (Lodd. Ex Lindl.) Munro), Bai Zi Ren (Semen of Platycladus orientalis (L.) Franco) and Fu Ling (sclerotium of Poria cocos (Schw.)Wolf). This study aimed to unravel the mechanism and material basis of NZN against traumatic brain injury. In this study, a 1H nuclear magnetic resonance (NMR) based metabolomic approach combined with systemsDock was employed to study the protective effect of NZN against traumatic brain injury using a cerebral concussion rat model. The morris water maze test and biochemical indexes were used to evaluate the efficacy of NZN. The results of morris water maze test suggested NZN can improve the spatial learning and memory of model rats, and the superoxide dismutas (SOD) and malonyldialdehyde (MDA) level indicated that the effect of NZN was related with the regulation of oxidative stress. Multivariate analysis revealed that the effect of NZN was related with regulation of 18 brain metabolites, and the corresponding metabolic pathways were further revealed by MetPA analysis. 13 serum absorbed components were found to hit the targets both related with the metabolic regulation and cerebral trauma through systemsDock-aided molecular docking experiments, and these compounds might be served as the active compounds in NZN against cerebral trauma. 1H-NMR based metabolomics and molecular docking provided the insights for the synergistic mechanisms and the potential active compounds of NZN in treating cerebral trauma. However, the bioactive compounds and their synergistic effect need to be further validated.


Impact of uric acid on immature platelet fraction in patients undergoing percutaneous coronary intervention.
Reticulated platelets have been involved in the pathophysiology of coronary artery disease (CAD). Immature platelet fraction (IPF) allows their measurement in daily clinical practice, although the factors conditioning their elevation are still largely unexplored. Serum uric acid (SUA) is the end product of purine metabolism, displaying a pro-oxidant and pro-inflammatory action and increasing the cardiovascular risk. The aim of our study was to investigate the impact of SUA on IPF levels in patients undergoing percutaneous coronary intervention (PCI), and their relationship with CAD. We enrolled a cohort of consecutive patients undergoing coronary angiography in a single center. Hyperuricemia was defined by SUA ≥ 6.5 mg/dl. Significant CAD was defined as at least 1 vessel stenosis >50%, while severe CAD was defined as left main and/or three-vessel disease. IPF was measured at admission by routine blood cells count (A Sysmex XE-2100). We included in our study 2217 patients, of whom 544 had high levels of SUA, while 1673 had normal levels. Hyperuricemics were older, with higher percentage of renal failure, hypertension, dilated cardiomyopathy or valvular disease as indication to angiography, higher levels of creatinine and C-reactive protein (p < 0.001, respectively) when compared to normouricemics. Immature platelet fraction (IPF) was significant higher in hyperuricemic patients (3.96% vs 3.59%, p = 0.004). A progressive direct increase in the IPF values was observed in relation to SUA levels (r = 0.101, p < 0.001), although at multivariate analysis, hyperuricemia did not result as an independent predictor of IPC in 3rd tertile (adjusted OR [95%CI] = 1.21 [0.85-1.71] P = 0.288). When stratifying hyperuricemics and normouricemics according to IPF tertiles (<2.3%; 2.3-3.9%; ≥ 4%), reticulated platelets were not associated to the prevalence of CAD (SUA ≥6.5:80.9 vs 79.3% vs 78.6%, p = 0.60; SUA < 6.5: 79.3% vs 81.3% vs 78.9%, p = 0.878) or severe CAD (SUA ≥6.5: 34.9% vs 38.9% vs 35.2%, p = 0.99; SUA < 6.5: 30.4% vs 33.5% vs 34%, p = 0.192), and the results were confirmed at multivariate analysis for CAD (SUA ≥6.5: adjusted OR [95%CI] = 1.11 [0.81-1.51] P = 0.524, SUA < 6.5: adjusted OR [95%CI] = 0.89 [0.75-1.05] P = 0.170) or severe CAD (SUA ≥6.5: adjusted OR [95%CI] = 1.03 [0.81-1.31] P = 0.795; SUA < 6.5: adjusted OR [95%CI] = 1.10 [0.96-1.26] P = 0.192). In the present study we found a direct relationship between SUA levels and IPF values; however, hyperuricemia did not result as an independent predictor of higher IPF tertile values. Neither in hyperuricemics nor in normouricemics higher IPF were independently associated to the prevalence of CAD or severe CAD.


A sensitive electrochemical strategy via multiple amplification reactions for the detection of E. coli O157: H7.
The sensitive and efficient strategy remains a central challenge for early diagnosis of pathogenic bacteria. Herein, an ultrasensitive electrochemical biosensor was proposed based on the multiple amplification strategy via the 3D DNA walker, rolling circle amplification (RCA) and hybridization chain reaction (HCR) for the accurate detection of Escherichiacoli O157:H7 (E. coli O157:H7). Firstly, the target sequence extracted from E. coli O157:H7 was transformed and amplified by the DNA walker firstly. Subsequently, a large number of transformed nucleic acid sequences were amplified by the RCA reaction. And then, the progress of HCR was triggered by every fragment in RCA products to form a long double-stranded DNA sequence to immobilize electrochemical indicators, generating a significantly enhanced electrochemical signal. As expected, a high sensitivity with a detection limit of 7 CFU/mL was achieved based on the proposed multiple amplification strategy, which is superior to most current methods for E. coli O157: H7 assay. The multiple amplification strategy could be readily expanded for the detection of various pathogenic bacteria, providing a new approach for early diagnosis of pathogenic microorganisms or other diseases.


Immunohistochemical Study of MUC1, MUC2 and MUC5AC Expression in Primary Breast Carcinoma.
Breast Cancer (BC) is the second most common cancer among women in India and accounts for 7% of global burden of BC and one-fifth of all Cancers (CA) among women in India. This study was conducted for studying the expression of MUC1, MUC2 and MUC5AC in breast carcinoma. Fifty cases of primary breast carcinoma diagnosed between years 2013 to 2015 were included in the study. Manual tissue array technique was applied for cases subjected to Immunohistochemistry (IHC). An analysis of the expression of IHC markers (MUC1, MUC2, MUC5AC, ER, PR and HER2/neu) was attempted. Results were subjected to statistical analysis. They were considered to be significant when the p-value was less than 0.05. The positivity for MUC1, MUC2 and MUC5AC in BC was 58%, 8% and 6% and for ER, PR and HER2 was 48%, 36% and 64% respectively. There was a significant correlation between MUC1 expression and ER and PR positivity. There was a significant correlation between MUC2 expression and ER positivity. No significant association was observed between MUC2 and PR expression, MUC5AC expression and ER and PR positivity. There was statistically significant correlation between negative MUC2 and MUC5AC expression and histopathological grade. It was noted that MUC2 and MUC5AC negative tumours were associated with higher tumour stage though not statistically significant. It was noted that MUC5AC negative tumours showed higher frequency of lymphovascular invasion though not statistically significant. Our experience with the present study highlights the role of mucins in the development and progression of BC.


Angiosarcoma of the heart: pericardial fluid cytology.
The unique cytomorphologic aspects of a cardiac angiosarcoma in pericardial fluid are presented. Smears and cell block preparations revealed clusters of malignant pleomorphic oval to spindle-shaped cells concentrically layered about amorphous acellular cores. The cytologic findings were correlated with histologic, immunohistochemical, and electron microscopic findings in the necropsy material.


Structural features of transiently modified beta-lactoglobulin relevant to the stable binding of large hydrophobic molecules.
Binding sites for hydrophobic molecules on bovine beta-lactoglobulin, and their susceptibility to temperature, were studied by using various spectroscopic probes. Binding of probes carrying a single fluorophore moiety, a single nitroxide moiety, or both moieties on the same molecule, was followed by EPR and fluorescence. The presence of a fatty acid side chain in the dual probes was found to be required for binding to beta-lactoglobulin. Binding occurred only after the protein was heated at temperatures below the threshold for its irreversible denaturation. Binding became extremely tight and stable upon cooling of the protein-probe mixture. Comparison among the various probes suggests that multiple binding sites for hydrophobes are present in the native protein, and in the partially-and reversibly-modified form of beta-lactoglobulin present in solution at neutral pH and subdenaturing temperatures. Thus, the specificity of hydrophobes binding to beta-lactoglobulin may be modulated by simple physical treatment of the protein.


Inhibition of the Human Neuronal Sodium Channel Nav1.9 by Arachidonyl-2-Chloroethylamide, An Analogue of Anandamide in a hNav1.9/rNav1.4 Chimera, An Experimental and in Silico Study.
Cannabinoids regulate analgesia, which has aroused much interest in identifying new pharmacological therapies in the management of refractory pain. Voltage-gated Na+ channels (Navs) play an important role in inflammatory and neuropathic pain. In particular, Nav1.9 is involved in nociception and the understanding of its pharmacology has lagged behind because it is difficult to express in heterologous systems. Here, we utilized the chimeric channel hNav1.9_C4, that comprises the extracellular and transmembrane domains of hNav1.9, co-expressed with the ß1 subunit on CHO-K1 cells to characterize the electrophysiological effects of ACEA, a synthetic surrogate of the endogenous cannabinoid anandamide. ACEA induced a tonic block, decelerated the fast inactivation, markedly shifted steady-state inactivation in the hyperpolarized direction, decreasing the window current and showed use-dependent block, with a high affinity for the inactivated state (ki = 0.84 µM). Thus, we argue that ACEA possess a local anaesthetic-like profile. To provide a mechanistic understanding of its mode of action at the molecular level, we combined induced fit docking with Monte Carlo simulations and electrostatic complementarity. In agreement with the experimental evidence, our computer simulations revealed that ACEA binds Tyr1599 of the local anaesthetics binding site of the hNav1.9, contacting residues that bind cannabinol (CBD) in the NavMs channel. ACEA adopted a conformation remarkably similar to the crystallographic conformation of anandamide on a non-homologous protein, obstructing the Na+ permeation pathway below the selectivity filter to occupy a highly conserved binding pocket at the intracellular side. These results describe a mechanism of action, possibly involved in cannabinoid analgesia.


Anterior inferior cerebellar artery aneurysms: six cases and a review of the literature.
Aneurysms of the anterior inferior cerebellar artery are rare. Six cases of anterior inferior cerebellar artery (AICA) aneurysms treated at one center are presented. The six cases of AICA aneurysms were surgically treated. The clinical features, surgical process, complications, and follow-up are demonstrated. Six patients with six AICA aneurysms were presented including one AVM accompanied aneurysm and one giant aneurysm. Five aneurysms had ruptured, one was unruptured. Five patients presented with subarachnoid hemorrhage (SAH) including two with intraventricular hemorrhaging and one with an intraparenchymal hematoma. One aneurysm was proximal, two were distal, and three were meatal. All cases were treated surgically. Retrosigmoid and far-lateral craniectomy were included. Navigation was accomplished through intraoperative ultrasound and fluorescent angiography. Resection of the aneurysm after clipping was significant. The most common postoperative deficit involved the cranial nerves in four patients. Follow-up was available for all patients for a mean of 68 months. SAH is the most common presentation. The relationship between the aneurysms and the meatus is an important factor for neurological dysfunction. 3D-CTA and MRA may be considered as diagnostic adjuncts. Several special surgical techniques used in our cases are worth noting. Endovascular therapy for AICA aneurysms is in the process of development and should be reserved for special cases.


Management of Coronary Disease in the Era of Transcatheter Aortic Valve Replacement: Comprehensive Review of the Literature.
Among the cohort of complex and multifaceted patients undergoing transcatheter aortic valve replacement (TAVR), the prevalence of coronary artery disease (CAD) ranges from 48% to 75%. However, optimal management of CAD in this setting has not been established. This article provides a comprehensive review of the literature to depict the actual knowledge on the subject of aortic stenosis and concomitant CAD. This article also aids heart teams in their decision-making process to appropriately manage these challenging patients with aortic stenosis and CAD. Upcoming randomized studies will clarify the influence of CAD, the best timing for percutaneous coronary intervention, and its impact on TAVR results.


Ulcerative colitis: shedding light on emerging agents and strategies in preclinical and early clinical development.
Ulcerative colitis (UC) is an inflammatory disease of the large intestine. Progress in preclinical therapeutic target discovery and clinical trial design has resulted in the approval of new therapies. Nonetheless, remission rates remain below 30% thus underlining the need for novel, more effective therapies. This paper reviews current experimental techniques available for drug testing in intestinal inflammation and examines new therapies in clinical development for the treatment of UC. The authors searched the literature for 'ulcerative colitis' AND 'preclinical' OR 'drug target/drug name' (i.e. infliximab, vedolizumab, IL-12, IL-23, JAK, etc.). Studies that included preclinical in vivo or in vitro experiments are discussed. The clinicaltrial.gov site was searched for 'ulcerative colitis' AND 'Recruiting' OR 'Active, not recruiting' AND 'Interventional (Clinical Trial)' AND 'early phase 1' OR 'phase 1' OR 'phase 2' OR 'phase 3.' Using in vivo, ex vivo, and/or in vitro models could increase the success rates of drugs moving to clinical trials, and hence increase the efficiency of this costly process. Selective JAK1 inhibitors, S1P modulators, and anti-p19 antibodies are the most promising options to improve treatment effectiveness. The development of drugs with gut-restricted exposure may provide increased efficacy and an improved safety.


An innovative postnatal risk assessment and corresponding care pathways in Preventive Child Healthcare.
This study aims to evaluate the effectiveness of an innovative postnatal risk assessment (the postnatal Rotterdam Reproductive Risk Reduction checklist: R4U) and corresponding care pathways in Preventive Child Healthcare (PCHC), along with PCHC professional satisfaction. Four PCHC organizations located in three municipalities with a higher adverse perinatal outcome than the national average were selected for participation. The study concerns a historically controlled study design. The study enrolled participants from September 2016 until December 2017. The historical cohort existed of children born in previous years from 2008 until 2016. The outcome measure was defined as catch-up growth: more than 0.67 standard deviation score weight for height increase in the first 6 months of life. PCHC professional opinion was assessed with a digital survey. After the inclusion period, 1,953 children were included in the intervention cohort and 7,436 children in the historical cohort. Catch-up growth was significantly less common in the intervention cohort; 14.9% versus 19.5% in the historical cohort (p < 0.001). A regression sensitivity analysis, using matching, showed an odds ratio of 0.957 (95% CI 0.938-0.976) for the intervention cohort. In the survey, 74 PCHC physicians and nurses participated; most of them were neutral concerning the benefits of the postnatal R4U. This study shows that the implementation of a novel postnatal risk assessment including in PCHC is feasible and effective. Final efforts to ensure a widespread implementation should be taken. PCHC offers a unique opportunity to recognize and address risk factors for growth and development in children and to implement care pathways. Effective and widely implemented risk assessments in antenatal and PCHC are scarce. To our knowledge, this kind of evidence-based postnatal risk assessment has not been implemented in PCHC before and seizes the opportunity to prevent catch-up growth and its long-term effects.


Application of the post-implantation rat embryo culture system to in vitro teratogenicity testing.
Originally developed for studying basic mechanisms in developmental biology, the post-implantation embryo culture system has been extended and applied to the testing of chemicals in the field of prenatal toxicology. The endpoints used in a procedure that has been developed for the routine short-term assessment of teratogenicity in vitro are growth (crown-rump length), differentiation (somite number) and morphology (together with measurement of yolk-sac growth and vascularization) in rat embryos explanted on day 9.5 of gestation and cultured for 48 hr in 100% homologous rat serum containing the test compound. Studies involving exposure to trichlorophenoxyacetic acid and to acetylsalicylic acid demonstrate the ability of this system to distinguish between non-specific toxicity and specific effects on development.


Peritoneal dialysis in an ageing population: a 10-year experience.
Chronic kidney disease (CKD) is becoming increasingly prevalent and there are increasing numbers of older patients with advanced CKD. Peritoneal dialysis (PD) is a potential treatment. This study aims to compare PD outcomes in age-defined populations in the largest PD centre in the Republic of Ireland over 10 years. We retrospectively identified all adult patients, over the age of 50 years, who commenced PD as their first modality of renal replacement therapy (RRT) between 1 January 1998 and 31 December 2008 at our institution. Primary outcome was patient survival; secondary outcomes were technique failure, peritonitis-free survival, transplantation and hospitalisations. One hundred and forty-eight patients with a mean age of 63 years were included. Twenty-two patients were on assisted PD, the majority of whom were aged 70 years or over (P = 0.001). There were no differences in patient survival or technique failure by age group, Charlson Co-Morbidity Index (CCI), modified-CCI or adjusted CCI. Renal transplantation occurred predominantly in younger patients (P = 0.001) with lower m-CCI (P = 0.001) and a-CCI (P = 0.002) who performed PD independently (P = 0.004). Older patients required longer hospital stays to initiate PD (P = 0.004). Assisted PD was not associated with an increase in early complications or technique failure but death rates were higher (P = 0.002). This study shows PD to be an acceptable modality of renal replacement therapy in elderly patients, with no observed differences in survival, technique survival or complication rates. Co-morbidities appear to play a stronger role in predicting survival than age alone. Assisted PD is a viable option in those unable to undergo PD independently.


Acquisition of mitochondrial DNA by a transformation vector for Ustilago violacea.
Plasmid pUCH1 is a 5.2-kb pUC18 construct bearing the hygB gene fused to a promoter from Cochliobolus heterostrophus. Haploid cells of the basidiomycete, Ustilago violacea, were transformed with this plasmid. In addition to multiple integrations of plasmid sequences into U. violacea nuclear DNA, vector sequences independent of the nuclear genome were indicated by Southern-blot analysis using all or part of pUCH1 as a probe. Hybridization also revealed intact pUCH1 and several larger derivatives in satellite bands from CsCl-bis-benzamide gradients of whole cellular DNA and in DNA from purified mitochondria [mitochondrial (mt) DNA preparations] of transformed U. violacea; circular DNAs consistent with the sizes of DNAs in these satellite bands were seen in electron microscope analyses of the same mt DNA preparations as well. The plasmids could be detected in mt DNA preparations even after 30 generations of transformant growth under selective pressure. Transformation of Escherichia coli by these mt DNA preparations produced bacterial transformants bearing intact pUCH1, as well as several pUCH1 derivatives, including pUCH2, an approx. 8.0-kb plasmid. A 2.5-kb EcoRI fragment from pUCH2 showed only weak hybridization with pUCH1. This unique fragment did hybridize strongly with mt DNA from untransformed U. violacea. This derivative thus appears to have acquired mt sequences from U. violacea.


CSF orexin-A/hypocretin-1 concentrations in patients with intracerebral hemorrhage (ICH).
Orexins/hypocretins are neuropeptides that have various physiological effects, including the regulation of both the feeding behavior neuroendocrine functions and sleep-wakefulness cycle. Recent studies have suggested that the orexin system may also be involved in neuronal damage in the clinical setting and animal experiments. The aim of this study was to examine the role of the hypothalamic orexin-A/hypocretin-1 system in patients with intracerebral hemorrhage (ICH). The CSF orexin-A/hypocretin-1 levels were measured in 11 ICH patients. CSF orexin-A/hypocretin-1 levels were low in ICH patients during the 13 days following the ICH event. The mean CSF orexin-A/hypocretin-1 levels were 61.1+/-22.3 (S.D.) pg/ml (range 27.5-106.9 pg/ml). The decreasing in the CSF orexin-A/hypocretin-1 levels was not related to the severity of ICH. The CSF orexin-A/hypocretin-1 levels were lower in the thalamic hemorrhage patients than those in other patients (48.5+/-23.3 pg/ml vs. 65.2+/-21.2 pg/ml; p=0.03.) These data indicate that orexin-A/hypocretin-1 may therefore play an important role in the various physiological responses including sleep, feeding, and the overall metabolism in ICH patients.


Inferring the basis of binaural detection with a modified autoencoder.
The binaural system utilizes interaural timing cues to improve the detection of auditory signals presented in noise. In humans, the binaural mechanisms underlying this phenomenon cannot be directly measured and hence remain contentious. As an alternative, we trained modified autoencoder networks to mimic human-like behavior in a binaural detection task. The autoencoder architecture emphasizes interpretability and, hence, we "opened it up" to see if it could infer latent mechanisms underlying binaural detection. We found that the optimal networks automatically developed artificial neurons with sensitivity to timing cues and with dynamics consistent with a cross-correlation mechanism. These computations were similar to neural dynamics reported in animal models. That these computations emerged to account for human hearing attests to their generality as a solution for binaural signal detection. This study examines the utility of explanatory-driven neural network models and how they may be used to infer mechanisms of audition.


Immune checkpoint inhibition for the treatment of cancers: An update and critical review of ongoing clinical trials.
Advances in Cancer immunotherapy in the past few years include the development of medications that modulate immune checkpoint proteins. Cytotoxic T-lymphocyte antigen 4 (CTLA4), programmed cell death protein 1 (PD1), and programmed cell death ligand 1 (PD-L1) are three co-inhibitory receptors that are expressed in the tumor microenvironment. Immune checkpoint inhibitors (ICI) that target these biomarkers unleash the properties of effector T cells that are licensed to kill cancer cells. Immune checkpoint blockade has dramatically changed the treatment landscape of many cancers. In this Review, we describe the current data regarding clinical trials of ICIs in six important cancers, including hepatocellular carcinoma (HCC), renal cell cancer (RCC), hodgkin lymphoma (HL), non-hodgkin lymphoma (NHL), non-small cell lung cancer (NSCLC), and head and neck cancer carcinoma (HNSCC).


Byzantine Empire Economic Growth: Did Past Climate Change Play a Role?
Different chronicles of the Byzantine Empire's history have noted various economic data gleaned from historical documents and accounts of the Empire's existence. I provide conjectures on approximate real GDP per capita for the Empire over its existence from AD 300 to 1453. I use these to investigate whether climate forcing variables are associated with real GDP per capita fluctuations. Some hypotheses on factors that would have affected Byzantine economic performance are tested using climate/environmental factors in time series regression. The results support and confirm some findings on how the Byzantine economy may have been affected by periods of regional climate change. The online version contains supplementary material available at 10.1007/s10745-022-00343-3.


Dissecting the molecular control of Interleukin 6 signaling using the M1 cell line.
Interleukin 6 is the classical member of the IL-6 family of cytokines which triggers activation of the JAK/STAT signaling cascade in cells. IL-6 is a pleiotropic cytokine that acts on many cell types and plays a critical role in immune responses, inflammation, and haematopoiesis. Our understanding of the molecular mechanisms governing IL-6 signaling has been aided by numerous studies of this signal transduction pathway, including those utilising the M1 cell line. Here we discuss the studies that we and others have undertaken using the M1 line to examine IL-6 inducible genes, particularly those targets that acts as negative regulators of signaling. Finally, we present a model for the current understanding of the IL-6 signaling pathway at a structural and mechanistic level.


Association between nocturnal falls and hypnotic drug use in older patients at acute care hospitals.
Although hypnotic drug use is a known risk factor for falls, few reports have analyzed fall risk associated with individual hypnotic drugs after adjusting for confounding factors. While it is recommended that benzodiazepine receptor agonists not be prescribed for older adults, it is unknown whether melatonin receptor agonists and orexin receptor antagonists are safe in this population. Here, we aimed to assess the influence of various hypnotic drugs on fall risk in older patients admitted to acute care hospitals. We investigated the relationship between nocturnal falls and sleeping pill use in 8,044 hospitalized patients aged > 65 years. We used a propensity score matching method to homogenize characteristics of patients with and without nocturnal falls (n = 145 patients per group) using 24 extracted factors (excluding hypnotic drugs) as covariates. Our analysis of fall risk for each hypnotic drug revealed that benzodiazepine receptor agonists were the only drugs significantly associated with falls, suggesting that use of the drugs is a risk factor for falls in older adults (p = 0.003). In addition, a multivariate analysis of 24 selected factors, excluding hypnotic drugs, revealed that patients with advanced recurrent malignancies were at greatest risk of experiencing falls (OR: 2.62; 95% CI: 1.23-5.60; p = 0.013). Benzodiazepine receptor agonists should be avoided in older hospitalized patients since they increase fall risk, with melatonin receptor agonists and orexin receptor antagonists used instead. Particularly, fall risk associated with hypnotic drugs should be considered in patients with advanced recurrent malignancies.


A deletion in the Ctns gene causes renal tubular dysfunction and cystine accumulation in LEA/Tohm rats.
The Long-Evans Agouti (LEA/Tohm) rat has recently been established as a new rat model of type 2 diabetes. The onset of diabetes mellitus was observed only in male LEA/Tohm rats; however, urinary glucose appeared before the onset of diabetes. To clarify the genetic basis of urinary glucose, we performed genetic linkage analysis using (BN × LEA) F2 intercross progeny. A recessively acting locus responsible for urinary glucose excretion (ugl) was mapped to a 7.9 Mb region of chromosome 10, which contains the cystinosin (Ctns) gene. The Ctns gene encodes the cystine transporter, which transports cystine out of the lysosome and is responsible for nephropathic cystinosis in humans. Sequence analysis identified a 13-bp deletion in the Ctns gene, leading to a truncated and loss-of-function protein, which cause cystine accumulation in various tissues. We also developed a novel congenic rat strain harboring the Ctnsugl mutation on the F344 genetic background. Phenotypic analysis of F344-Ctnsugl rats indicated that the incidence of urinary glucose was 100% in both males and females at around 40 weeks of age, and marked cystine accumulation was observed in the tissues, as well as remarkable renal lesions and cystine crystals in the lysosomes of the renal cortex. Furthermore, treatment with cysteamine depleted the cystine contents in F344-Ctnsugl rat embryonic fibroblasts. These results indicated that the F344-Ctnsugl rat provides a novel rat model of cystinosis, which allows not only a better understanding of the pathogenesis and pathophysiology of cystinosis but will also contribute to the development of new therapies.


An ultrastructural study of dentinogenesis and amelogenesis in rat molar tooth germs cultured in vitro.
Molar tooth germs from three-day-old rats were cultured successfully for fourteen days, permitting the study of the development in vitro of both extracellular matrix and cellular elements such as odontoblasts and ameloblasts. The ultrastructure of the cultured tooth germs was compared with the ultrastructure of tooth germs in vivo at a comparable developmental stage. Progenitor cells of odontoblasts and ameloblasts were found to differentiate in vitro. Odontoblasts seemed to contain more lysosome-like bodies and fewer secretory granules than in vivo. They formed normally mineralizing dentine or a thick layer of dense, unmineralized predentine with incidentally some amorphous, extracellular material. Enamel was exclusively present opposite well developed dentine. It was often hyper- or hypomineralized and enamel rods were not as regularly shaped as in vivo. In places where no enamel formation had taken place, large amounts of amorphous extracellular material were sometimes seen. From these observations it can be concluded that cellular development in cultured tooth germs appeared more or less normal, but extracellular matrix formation and mineralization were sometimes disturbed.


The repair of UV-induced cyclobutane pyrimidine dimers in the individual genes Gart, Notch and white from isolated brain tissue of Drosophila melanogaster.
We have measured the induction and removal of UV-induced cyclobutane pyrimidine dimers from defined, DNA sequences in brains isolated from wild-type Drosophila melanogaster third instar larvae. Brains were exposed to a single dose of 500 J/m2 UVB and kept in the dark for up to 48 h. Within 48 h after irradiation, 50% of the dimers are removed from the actively transcribed genes Gart and Notch. Moreover, these kinetics are similar to the time course of dimer removal measured in the transcriptionally inactive white gene. It is further demonstrated that the genome overall is repaired at a similar rate. The results are discussed with respect to the in vivo irradiation of brains and to the data found for gene-specific repair in other eukaryotes.


Utilising multi-large omics data to elucidate biological mechanisms within multiple sclerosis genetic susceptibility loci.
Genome-wide association studies (GWAS) have succeeded in identifying over 200 susceptibility loci for multiple sclerosis (MS). However, the potential functional variants and the mechanisms by which these loci affect MS risk remain largely unexplained. We used summary data-based Mendelian randomisation to prioritise risk genes and infer potential biological mechanisms for MS risk loci. The data used consisted of DNA methylation (n = 1980) QTL (mQTL) and gene expression (n = 31,684) QTL (eQTL) derived from whole blood as well as MS GWAS summary statistics (14,802 cases, 26,703 controls). The findings were further evaluated using data derived from independent brain mQTL (n = 1160) and eQTL (n = 1194). In whole blood, we identified two independent genomic loci (lincRNA: RP11-326C3.13 and TNFSF14) with consistent genome-wide significant pleiotropic associations across different omics layers. In brain tissue, a similar effect for the RP11-326C3.13 locus was observed but not for TNFSF14, indicating a potential tissue-specific effect for the TNFSF14 locus. We provide in silico evidence for the putative biological mechanisms by which the identified DNA methylation sites and target genes are functionally relevant to MS development in different tissues. Future research targeting these genes and DNA methylation sites will determine their roles in the pathophysiology of MS.


Comparative distalization effects of Jones jig and pendulum appliances.
In this study, we compared the dentoalveolar changes of Class II patients treated with Jones jig and pendulum appliances. The experimental group comprised 40 Class II malocclusion subjects, divided into 2 groups: group 1 consisted of 20 patients (11 boys, 9 girls) at a mean pretreatment age of 13.17 years, treated with the Jones jig appliance for 0.91 years; group 2 comprised 20 patients (8 boys, 12 girls) at a mean pretreatment age of 13.98 years, treated with the pendulum appliance for 1.18 years. Only active treatment time of molar distalization was evaluated in the predistalization and postdistalization lateral cephalograms. Molar, second premolar, and incisor angular and linear variables were obtained. The intergroup treatment changes in these variables were compared with independent t tests. The maxillary second premolars showed greater mesial tipping and extrusion in the Jones jig group, indicating more anchorage loss during molar distalization with this appliance. The amounts and the monthly rates of molar distalization were similar in both groups. The Jones jig group showed greater mesial tipping and extrusion of the maxillary second premolars. The mean amounts and the monthly rates of first molar distalization were similar in both groups.


Prospective Study of Q Switched Alexandrite Laser 755 nm and V Beam Pulsed Dye Laser 595 nm in Dermatofibroma.
Pulsed dye and carbon dioxide lasers have been applied in dermatofibroma with clinical improvement. We treated 23 dermatofibromas two times at a 4-week interval with Q-Switched alexandrite laser 755nm (7.5J/cm2, 3mm, 50ms). V Beam pulsed dye laser with a wavelength of 595nm was used for the residual erythema (10-11J/cm2, 7mm, 1.5ms). A partial attenuation of brown colour was observed in 9 patients and complete disappearance of brown colour in 14 patients. Patient satisfaction was very high. Fifteen patients felt a decrease in hardening of dermatofibroma after treatment. A pigment network in dermoscopy was observed in all patients before treatment and no one after treatment. A combined treatment using both V Beam pulsed dye laser and Q-Switched alexandrite laser may be a therapeutic option to reduce the aesthetic effect of dermatofibroma with a high patient satisfaction and good cosmetic outcomes.


A task level fusion autonomous switching mechanism.
Positioning technology is an important component of environmental perception. It is also the basis for autonomous decision-making and motion control of firefighting robots. However, some issues such as positioning in indoor scenarios still remain inherent challenges. The positioning accuracy of the fire emergency reaction dispatching (FERD) system is far from adequate to support some applications for firefighting and rescue in indoor scenarios with multiple obstacles. To solve this problem, this paper proposes a fusion module based on the Blackboard architecture. This module aims to improve the positioning accuracy of a single sensor of the unmanned vehicles within the FERD system. To reduce the risk of autonomous decision-making of the unmanned vehicles, this module uses a comprehensive manner of multiple channels to complement or correct the positioning of the firefighting robots. Specifically, this module has been developed to fusion a variety of relevant processes for precise positioning. This process mainly includes six strategies. These strategies are the denoising, spatial alignment, confidence degree update, observation filtering, data fusion, and fusion decision. These strategies merge with the current scenarios-related parameter data, empirical data on sensor errors, and information to form a series of norms. This paper then proceeds to gain experience data with the confidence degree, error of different sensors, and timeliness of this module by training in an indoor scenario with multiple obstacles. This process is from data of multiple sensors (bottom-level) to control decisions knowledge-based (up-level). This process can obtain globally optimal positioning results. Finally, this paper evaluates the performance of this fusion module for the FERD system. The experimental results show that this fusion module can effectively improve positioning accuracy in an indoor scenario with multiple obstacles. Code is available at https://github.com/lvbingyu-zeze/gopath/tree/master.


Impact of lockdown due to COVID-19 pandemic on groundwater salinity in Punjab, India: some hydrogeoethics issues.
In the present study, a total of 48 groundwater samples (13 from shallow aquifers depth < 50 m and 35 samples from deep aquifers in the depth range 50-200 m) were collected from three industrial dominant districts (Ludhiana, Jalandhar and Moga) of Punjab after the lockdown period and before the start of southwest monsoon in the month of June, 2020 (pre-monsoon). The values for total dissolved solids (TDS) observed in Monsoon season (August, 2020) and November-December, 2019 (post-monsoon) were compared with the values taken in June, 2020 (pre-monsoon) to see the impact of lockdown due to COVID-19 pandemic on groundwater salinity. ~ 60% of samples were found to have TDS values more than acceptable limit (500 mg/l) before lockdown (post-monsoon season of 2019) period and after or during lockdown period (June, 2020) number of samples more than the acceptable limit (500 mg/l) reduced to 45%. Average TDS values reduced by 25% in shallow aquifers after lockdown and area under TDS values in acceptable limit (500 mg/l) increased by 23% of samples as compared to the TDS values found in monsoon season of year 2019. In deeper aquifers, increase of only 3% area under TDS values in acceptable limit of 500 mg/l was found. Reductions in TDS values in shallow aquifers clearly show that there is an urgent need for proper management of salinity causing elements and regulating these to check groundwater contaminations using the holistic and hydro-geoethical approach.


Functional network properties of the auditory cortex.
The auditory system transforms auditory stimuli from the external environment into perceptual auditory objects. Recent studies have focused on the contribution of the auditory cortex to this transformation. Other studies have yielded important insights into the contributions of neural activity in the auditory cortex to cognition and decision-making. However, despite this important work, the relationship between auditory-cortex activity and behavior/perception has not been fully elucidated. Two of the more important gaps in our understanding are (1) the specific and differential contributions of different fields of the auditory cortex to auditory perception and behavior and (2) the way networks of auditory neurons impact and facilitate auditory information processing. Here, we focus on recent work from non-human-primate models of hearing and review work related to these gaps and put forth challenges to further our understanding of how single-unit activity and network activity in different cortical fields contribution to behavior and perception.


Synthesis of an inhibitor of human immunodeficiency virus infection.
Anti-HIV effects of lentinan sulfate were investigated by using an HTLV-I-carrying cell line, MT-4, in vitro. Lentinan, a fungal branched (1----3)-beta-D-glucan, was sulfated to various degrees by means of two kinds of procedures using piperidine N-sulfonic acid in dimethyl sulfoxide or chlorosulfonic acid in pyridine. Lentinan sulfate with a sulfur content of more than 13.9% effectively prevented HIV-induced cytopathic effects (CPE) at concentrations of more than 3.3 micrograms/ml. However, low-substituted lentinan sulfate did not prevent HIV-induced CPE at any concentration tested. When the countercation was 50% Na+ and 50% pyridinium ion, the inhibitory capacity was low. Anticoagulant activity of the lentinan sulfate was also assessed.


Mineral composition and heavy metal contamination of sediments originating from radium rich formation water.
Radium rich formation water is often associated with fossil fuels as crude oil, natural gas and hard coal. As a result of fossil fuels exploitation high amount of such water is released into environment. In spite of the high radium content such waters create a serious radiation risk neither to humans nor biota directly. First and foremost due to very high mineralization they are not drinkable at all. But after discharge chemical and physical conditions are substantially changed and sediments which additionally concentrated radium are arising. Due to features of technological processes such phenomenon is very intensive in underground coal mining where huge volume of such water must be pumped into surface in order to keep underground galleries dry. Slightly different situation occurs in oil rigs, but finally also huge volume of so called process water is pumped into environment. Regardless their origin arising sediments often contain activity concentration of radium isotopes exceeding the clearance levels set for naturally occurring radioactive materials (NORM) (Council Directive, 2013). The analysis of metals and minerals content showed that besides radioactivity such sediments contain high amount of metals geochemically similar to radium as barium, strontium and lead. Correlation analysis proved that main mechanism leading to sediment creation is co-precipitation radium with these metals as a sulfate. The absorption on clay minerals is negligible even when barium is not present in significant quantities. Owing to very low solubility of sulfates radium accumulated in this way should not migrate into environment in the neighborhood of a site where such sediment were deposited.


Does Implant Surface Texture Affect the Risk of Capsular Contracture in Subglandular Breast Augmentation and Breast Augmentation-Mastopexy?
Previous studies have reported decreased rates of capsular contracture associated with the use of textured surface breast implants placed in the subglandular plane during breast augmentation. However, since the publication of these studies, our understanding of the pathophysiology of capsular contracture, as well as the surgical techniques utilized to minimize bacterial contamination of the implant, have advanced considerably. The purpose of this study was to re-evaluate the relation between implant surface texturization and capsular contracture rates for breast implants placed in the subglandular plane during primary breast augmentation. Retrospective chart review was performed of all primary subglandular breast augmentation procedures involving the use of either smooth or textured round silicone gel implants, with or without simultaneous mastopexy. The primary outcome measures included clinically significant capsular contracture (Baker grade III/IV) and revision surgery for capsular contracture. Between 2010 and 2017, 526 patients underwent primary subglandular breast augmentation with either smooth (n = 212) or textured (n = 314) round silicone gel implants; 248 patients underwent breast augmentation, whereas 278 underwent breast augmentation-mastopexy. Average follow-up was 756 days in the textured group and 461 days in the smooth group. Five cases of capsular contracture were observed in the textured group, and 7 cases of capsular contracture were observed in the smooth group (P = 0.20). Smooth surface implants placed in the subglandular plane were not at a significantly increased risk of capsular contracture compared with textured surface implants. We suggest that adherence to a surgical technique focused on minimizing bacterial contamination of the implant is of greater clinical significance than implant surface characteristics when discussing capsular contracture.


Cryogenic blockade of the central nucleus of the amygdala attenuates aversively conditioned blood pressure and respiratory responses.
The central nucleus of the amygdala (ACE) was reversibly blocked during extinction of an aversively conditioned cardiorespiratory response in unanesthetized, freely moving cats. Cryoprobes were positioned bilaterally in the ACE of 4 cats and in the nucleus entopeduncularis of 1 cat. Blood pressure typically showed biphasic changes in response to the conditioned stimulus (CS) during non-cooling trials. Blood pressure initially dropped and then rose. Heart rate consistently dropped, and respiratory rate increased in response to the CS. ACE cooling did not alter the pre-CS baseline blood pressure, heart rate or respiratory timing, but changed the cardiorespiratory response to the CS. During ACE cooling, blood pressure and respiratory responses were greatly attenuated or abolished. No significant effect on the heart rate response was observed during ACE cooling. Cooling of a nearby structure, the nucleus entopeduncularis, did not affect blood pressure, heart rate or respiratory responses to the CS. These results support the hypothesis that the ACE plays a role in both cardiovascular and respiratory regulation during conditioned aversive responses. The study also suggests that, in cats, the predominant influence of the ACE on cardiovascular control is on blood pressure rather than on heart rate regulation.


Filling the gaps in knowledge translation: Physical therapy recommendations for individuals with spinal muscular atrophy compared to standard of care guidelines.
This study describes the current landscape of physical therapy practice recommendations in the United States for children with spinal muscular atrophy (SMA) and their relationship to current SMA standard of care (SMA-SOC) guidelines. Pediatric physical therapists were surveyed to determine their knowledge of SMA-SOC guidelines, and the type, duration and frequency of intervention they recommend for children with SMA, as well as perceived barriers and facilitators to progress in physical therapy. Physical therapists recommend five key intervention areas for individuals with SMA; however discrepancies exist between the SOC recommended intervention parameters and respondents' reported frequency and duration of recommendations. After individuals with SMA initiated disease modifying pharmacotherapies, a majority of physical therapist respondents recommended increases in both frequency and duration of interventions. Nearly all respondents reported that familiarity with SOC guidelines was beneficial to their practice. The primary facilitator to progress was parent/caregiver support, while the primary barrier was limited access to resources. Variation in practice exists regarding care for those with SMA, particularly in the areas of frequency and duration of specific interventions. These findings can guide educational initiatives, identify future research needs and further inform SMA-SOC and best-practice rehabilitation management.


Electronystagmographic criteria in neuro-otological diagnosis. 2. Central nervous system lesions.
Direct current electronystagmographic recordings of spontaneous nystagmus in light, in darkness, and with eye closure have been carried out on (a) 33 patients with acoustic neurinomata pressing on the brain stem, and (b) 10 patients with lesions involving the brain stem at a high level. Patterns of response characteristics of each group have been identified in 21 out of 28 cases of group a, the spontaneous nystagmus present in light was abolished by eye closure and inhibited in darkness, nystagmus being absent in the remaining five; in group b the greater proportion (70-80%) of patients presented with spontaneous nystagmus in light which was abolished by both eye closure and darkness.


Aberrant Origin of the Distal Anterior Cerebral Artery from the Middle Cerebral Artery Related to Obstruction of Bilateral Proximal Anterior Cerebral Arteries: A Case Report.
Aberrant origin of the distal anterior cerebral artery (ACA) arising from the middle cerebral artery (MCA) is extremely rare. A 74-year-old woman with a sudden onset of left-sided weakness was admitted to the emergency department. Angiography revealed an unusual course of the distal ACA originating from the MCA with bilateral obstruction of the proximal segment of the ACA and simultaneous occurrence of infarction in the ACA and MCA territories. Knowledge of a rare vascular variation or anomaly could help understand brain imaging, which has an unusual involvement of vascular territories, performed in patients with acute ischemic stroke.


First identification of Toll-like receptor-4 in avian brain: evolution of lipopolysaccharide recognition and inflammation-dependent responses.
In this work, we examine the effects of lipopolysaccharide (LPS) treatment on nerve cells of chick embryo used as a universal avian model. We demonstrate that LPS leads to a dramatic cell loss in primary cultures of both glia and neurons, isolated from chick embryos. Toxic effects appear to be mediated by the Toll-like receptor (TLR)-4 complex, expressed in both glial and neuronal cells, since after TLR-4 silencing by RNA interference experiments LPS-induced cytotoxicity was prevented. The role of nitric oxide in LPS-induced cell damage has also been investigated. These results demonstrate, for the first time in avian nerve cells, the surface expression of TLR-4 and its role as a pattern recognition receptor involved in LPS-induced cell responses in a similar manner to that observed in mammals.


Carcinogenicity tests of fecapentaene-12 in mice and rats.
Fecapentaenes, a class of direct-acting bacterial mutagens, have been isolated from the feces and intestinal tract of humans on a Western meat-containing diet. Two bioassays to test pure fecapentaene-12 (FP-12) for carcinogenicity were performed. FP-12 in dimethylsulfoxide (DMSO) solution was injected i.p. into newborn ICR/MA mice on days 1, 3, 7, 10, 14 and 21. The mice killed after 21 months had neoplasms in liver, lung, glandular stomach and subcutaneous fibrosarcoma. Intrarectal (i.r.) infusion of FP-12 in an aqueous vehicle into male F344 rats for 71 weeks, and killing the rats after 21 weeks more, displayed no evidence of neoplasia associated with FP-12 exposure. The positive control, N-nitrosomethylurea (NMU), given i.r. as 4 2-mg doses in 2 weeks, as expected, yielded multiple colonic neoplasms in less than 11 months. Fecapentaene may exert its effect in bacteria and in newborn mice through the generation of hydroxy radicals. However, adult rodent and human colon may have adequate biochemical defense mechanisms against low level, even continuous exposures to chemicals like FP-12, and thus be at low risk of neoplasia, as was found.


Indolent infectious tenosynovitis afflicting rheumatoid patients treated with tumor necrosis factor inhibitors: case report.
Tumor necrosis factor (TNF) is a cytokine associated with the pathogenesis of rheumatoid arthritis. Tumor necrosis factor inhibitors have become important biological treatments that favorably alter the natural history of rheumatoid disease. Side effects include an increased risk of malignancy and infection, particularly tuberculosis. We present 2 patients with rheumatoid arthritis on TNF inhibitors in whom flares of wrist tenosynovitis, initially diagnosed as rheumatoid disease exacerbations, were caused by infections with uncommon opportunistic pathogens. Diagnostic and treatment recommendations for this subset of rheumatoid patients are discussed.


Implementing and Evaluating a Stakeholder-Driven Community Diffusion-Informed Early Childhood Intervention to Prevent Obesity, Cuyahoga County, Ohio, 2018-2020.
The purpose of this article is to demonstrate and evaluate aspects of a Stakeholder-Driven Community Diffusion (SDCD)-informed intervention with a group of stakeholders drawn from a large coalition seeking a novel approach for promoting policy, systems, and environmental-level change. The objectives were to implement an SDCD intervention, assess changes in participants' perspectives, and evaluate where the group's actions fit within the context of a systems map that the group created during the intervention. An SDCD-informed intervention convened 12 multisector stakeholders from the Early Ages Healthy Stages coalition in Cuyahoga County, Ohio. They participated in group model building activities to promote systems thinking related to childhood obesity prevention, reviewed evidence about topics of interest to the group, and were provided with technical assistance and seed funding to guide the selection and implementation of actions prioritized by the group. Data were collected via meeting notes and group model building outputs to demonstrate implementation and action prioritization; online surveys and qualitative interviews to measure perspective change among stakeholders; and a follow-up survey to the broader coalition assessing actions coalition members were taking. An SDCD-informed intervention guided the development of a systems map and the selection of 4 actions: 1) develop a better understanding of the local early childcare environment; 2) assess the effectiveness and impact of Ohio Healthy Programs (OHP); 3) advocate for OHP and improved early childhood education quality; and 4) hold OHP designees accountable to high-quality programming. Data collected from surveys and interviews showed increased awareness of programs, resources, and collaboration opportunities among stakeholders. Follow-up survey results showed ongoing coalition action throughout the systems map. Using an SDCD-informed intervention among a coalition of community stakeholders provided a unique approach for implementing, assessing, and analyzing collaborative efforts to prevent childhood obesity in Cuyahoga County. Our approach can be applied to help researchers and stakeholders improve efforts to address childhood obesity in their communities.


Strategies on how to maximize the moment as a junior faculty.
Transitioning from a postdoctoral to a faculty position in science, technology, engineering, and mathematics (STEM) is a cumbersome process, and it is easy for postdocs to become lost in the sea of opportunities. Here we provide a blueprint to navigate this transition and suggestions to survive in the STEM faculty arena.


Vaginal douching as a potential risk factor for tubal ectopic pregnancy.
The incidence of ectopic pregnancy in the United States has more than doubled in the past decade. Because a previous study has suggested that the practice of vaginal douching may increase the risk of pelvic inflammatory disease, a condition known to predispose to ectopic pregnancy, and because the sale of commercial douching products in the United States has more than tripled since 1974, we investigated this practice as a possible risk factor. We interviewed 155 women who had a tubal ectopic pregnancy treated at five Seattle hospitals between 1975 and 1979 as to their reproductive, contraceptive, and medical histories, demographic characteristics, and personal hygiene practices. During the same period, 456 women who were delivered of a baby in King County were identified from Vital Records and interviewed as controls. A higher proportion of cases than controls reported ever having douched in the past. Cases also douched more frequently than controls. After simultaneous adjusting for confounding factors in our data by means of a multiple logistic regression technique, the risk of tubal ectopic pregnancy for women who douched at least weekly was twice that of women who never douched (95% confidence interval = 1.03 to 4.00). The risk for women who used commercial douches on a weekly basis was 4.4 (95% confidence interval = 1.6 to 12.7) the risk for women who never douched.


When the Tallamys Met John French: Translating, Printing, and Reading The Art of Distillation.
Centered on the life story of the Tallamy family's copy of John French's The Art of Distillation (London, 1651), this article explores translation, print, and medical reading in early modern England. It traces the adaptation and reuse of textual and practical knowledge across linguistic, geographical, gender, and spatial boundaries and shines light on the scientific labor of translators, technicians, and householders, historical actors who are so often hidden by structures of the archival record. By historically situating translation, reading, and writing practices, it joins recent calls to view each translation as an independent text shaped by new contextual settings. It concludes by offering the concept of "knowledge itineraries" as a framework for analyzing long-view connected histories of knowledge transfer across time and space.


Renal pelvic cancer: a review of 611 patients treated in Illinois 1975-1985. Cancer Incidence and End Results Committee.
Renal pelvic transitional cell carcinoma constitutes about 7 percent of all kidney cancer. This report is a summary of 611 Illinois patients with this tumor treated between 1975 and 1985. Overall, the five-year relative survival rate was 62 percent and the observed five-year rate was 48 percent. Stage was a major determinant of survival, as expected, in these cancer patients. The Illinois experience is reviewed and compared with the accumulated literature experience with renal pelvic cancers since 1944.


Reduced 'gonadotrophin response to releasing hormone' after chronic administration to impotent men.
Ten endocrinologically normal men with secondary sexual impotence were given 500 microng LHRH subcutaneously every 8 h. After 4 weeks treatment the LH response to 500 microng LHRH was reduced from a peak of 35.7+/-5.2 to 16.8+/-3.5 mu/ml (P less than 0.01) and the FSH response from 4.2+/-0.93 to 2.39+/-0.4 mu/ml (P greater than 0.01). Circulating total testosterone, oestradiol, prolactin and sex hormone binding globulin showed no significant changes. Whether this inability of the pituitary to maintain it s response to LHRH is peculiar to impotent men requires further study.


Interleukin-6 in Cerebrospinal Fluid Small Extracellular Vesicles as a Potential Biomarker for Prognosis of Aneurysmal Subarachnoid Haemorrhage.
Aneurysmal subarachnoid hemorrhage (aSAH) is a severe form of stroke characterized by high rates of mortality and disability. Identifying circulating biomarkers is helpful to improve outcomes. In this study, for the first time, we identify interleukin-6 (IL-6) in cerebrospinal fluid (CSF) small extracellular vesicles (sEVs) as potential biomarkers for prognosis of aSAH. We extracted small extracellular vesicles from the CSF of 103 aSAH patients and 40 healthy controls in a prospective observational study. Subsequently, we measured IL-6sEVs levels using an enzyme-linked immunosorbent assay. Results were statistically analyzed to determine the function of IL-6sEVs for disease monitoring of aSAH. CSF IL-6 sEVs showed distinct pattern differences between healthy controls and aSAH patients. The concentration of IL-6sEVs in CSF is significantly correlated with the severity of aSAH patients. The areas under the receiver operating characteristic curves of IL-6sEVs for identifying severe aSAH patient from aSAH patients were 0.900. After multivariate logistic regression analysis, IL-6sEVs were associated with neurological outcome at 1 year. IL-6sEVs levels were greater and positively associated with disease processes and outcome. There is a neuroinflammatory cascade in aSAH patients. IL-6sEVs in CSF may be a biomarker for the progression of aSAH.


The presence of pharmaceuticals in the environment due to human use--present knowledge and future challenges.
Intensive research on pharmaceuticals in the environment started about 15 years ago. Since then a vast amount of literature has been published. The input and presence of active pharmaceutical ingredients (APIs) and their fate in the environment were and is still of high interest. As it has been extensively demonstrated that the active compounds are present in the environment some of the research interest has moved from analysis of the compounds, which is still undertaken, to effect studies in the lab and in field trials. It has been found that environmental concentrations can cause effects in wildlife if proper tools are applied for effect assessment. The question of mixture toxicity has gained more and more attention. It has been learned that classical tests may underestimate effects and risks. Work has been done in the field of risk assessment and risk management. As for risk management strategies to eliminate pharmaceuticals from wastewater or from the effluent of sewage treatment plants have been proposed and investigated. A tremendous amount of literature can now be found describing technical management measures such as oxidative or photolytic effluent treatment, filtering techniques, and application of charcoal. It has been learned however, that each of these approaches has its specific shortcomings. Therefore, additional approaches such as including people handling and using the compounds, and focusing on the properties of the compounds ("green pharmacy") came into focus. Accordingly, this review gives an overview of the present state of knowledge presenting typical results and lines of discussion. This review makes no claim to give a complete overview including the full detailed body of knowledge of pharmaceuticals in the environment. Rather, it addresses important and typical topics to stimulate discussion.


UV-curable low surface energy fluorinated polycarbonate-based polyurethane dispersion.
UV-curable low surface energy fluorinated polycarbonate-based polyurethane dispersions were synthesized by incorporating a hydroxy-terminated perfluoropolyether (PFPE) into the soft segment of polyurethane. The effects of the PFPE content on the UV-curing behavior, physical, surface, thermal properties and refractive index were investigated. The UV-curing behavior was analyzed by photo-differential scanning calorimetry. The surface free energy of the UV-cured film, which is related to the water or oil repellency, was calculated from contact angle measurements using the Lewis acid-base three liquids method. The surface free energy decreased significantly with increasing fluorine concentration because PFPE in the soft segment was tailored to the surface and produced a UV-cured film with a hydrophobic fluorine enriched surface, as confirmed by X-ray photoelectron spectroscopy. With increasing the fluorine content, the refractive indices of UV-cured films decreased. However, the UV-curing rate and final conversion was decreased with increasing contents of PFPE, which resulted in the decrease of the glass transition temperature (T(g)), crosslink density, tensile strength and surface hardness.


Ecotoxicological evaluation of magnetic ionic liquids.
Although magnetic ionic liquids (MILs) are not yet industrially applied, their continued development and eventual commercial use may lead to their appearance into the aquatic ecosystem through accidental spills or effluents, consequently promoting aquatic contaminations. Furthermore, the deficient information and uncertainty surrounding the environmental impact of MILs could be a major barrier to their widespread industrial application and international registration. Thus, in the present work, a range of cholinium salt derivatives with magnetic properties was synthesized and their ecotoxicity was evaluated towards the luminescent bacteria Vibrio fischeri. The results suggest that all MILs structures tested are moderately toxic, or even toxic, to the bacteria. Furthermore, their toxicity is highly dependent on the structural modifications of the cation, namely the alkyl side chain length and the number of hydroxyethyl groups, as well as the atomic number of the metal anion. Finally, from the magnetic anions evaluated, the [MnCl4]2- is the less toxic. In order to improve the knowledge for the prospective design of environmentally safer MILs, it is important to expand this study to other aquatic organisms at different trophic levels.


Efficacy and safety of weekly intravenous nanoparticle albumin-bound paclitaxel for non-small cell lung cancer patients who have failed at least two prior systemic treatments.
The study was conducted to evaluate the efficacy and safety of weekly intravenous nanoparticle albumin-bound paclitaxel (NAB-paclitaxel) treatment in patients with advanced non-small-cell lung cancer (NSCLC) who have undergone multi-line therapy, and to investigate the association of secreted protein acidic and rich in cysteine (SPARC) expression status with clinical outcome. Sixty-four patients who received NAB-paclitaxel treatment (130 mg/m2 on days 1 and 8 of a 21 day cycle) as third line or further systemic treatment from 1 May 2011 to 30 June 2014 were included in this retrospective analysis. Tumor tissue was available in 28 patients for analysis of SPARC expression by immunohistochemistry. Sixty-two patients had response evaluation and complete survival follow-up data; 83.9% received the weekly NAB-paclitaxel as fourth-line treatment or beyond. The objective response and disease control rates (n = 62) were 16.1% (10/62) and 64.5% (40/62), respectively. The median progression-free and overall survival rates were 3.7 (95% confidence interval 2.6-4.8) and 9.8 months (95% confidence interval 6.9-12.8), respectively. Previous treatment with taxane did not affect the response to NAB-paclitaxel. The main grade 3-4 toxicities experienced were neutropenia (9.4%) and leukopenia (7.8%). Patients with SPARC expression in tumor stroma but not in cancer cells had poorer progression-free survival compared with those with negative SPARC expression in tumor stroma cells (3.3 vs. 5.0 months, P = 0.036). Weekly NAB-paclitaxel might be effective for heavily pretreated NSCLC patients. SPARC expression in tumor stroma cells might be a potential negative predictor of NAB-paclitaxel.


An analytical perspective on favoured synthetic routes to the psychoactive tryptamines.
Many tryptamine derivatives are known to induce altered states of consciousness and are increasingly of interest in forensic and neurobiological studies. The analytical chemistry of certain synthetic routes to the tryptamines is discussed and likely side products and impurities identified, where literature reports are available. Recent examples from the authors' laboratory are presented to highlight future prospects and implications for analytical procedures. The aim of this review is to provide the analytical chemist with the foundation chemistry and some analytical targets to be able to undertake direct characterisation of products and intermediates. These might become available from interdiction of clandestine operations in a forensic environment or during the synthesis of the tryptamines for investigative neurobiological and clinical procedures.


Identification of a ganglioside recognition domain of tetanus toxin using a novel ganglioside photoaffinity ligand.
Tetanus toxin entry into vertebrate motorneurons may involve binding of neuronal surface gangliosides containing the "1b" substructure (a NeuAcalpha2,8NeuAc group on an internal galactose residue). The domains of tetanus toxin involved in ganglioside binding are known to reside within the carboxyl-terminal half of the toxin's heavy chain ("C fragment"). We developed a novel photoaffinity reagent based upon the structure of the 1b ganglioside GD1b (125I-azido-GD1b) to define the ganglioside-binding domains of tetanus toxin. Using this ligand, we observed radiolabeling of tetanus toxin C fragment which could be specifically inhibited by a ganglioside of the 1b series (GT1b), but not by a non-1b series ganglioside (GM3). When tetanus toxin C fragment was proteolyzed with clostripain, whether before or after reaction with 125I-azido-GD1b, a radiolabeled band was observed by SDS-polyacrylamide gel electrophoresis autoradiography, which was selectively inhibited by GT1b. Protein sequencing of proteolyzed tetanus toxin C fragment co-migrating with that band revealed the carboxyl-terminal 34 amino acid residues of tetanus toxin. Matrix-assisted laser desorption/ionization mass spectrometry of a photoaffinity labeled synthetic polypeptide representing the 34-amino acid domain revealed modification at a single residue (His1293). We propose that this domain of tetanus toxin is sufficient for ganglioside binding.


[Relation of arterial pressure, blood cholesterol and glucose tolerance to body weight (based on data from a population preventive study)].
The relationship of arterial blood pressure and blood levels of cholesterol and glucose (1 hour after a 75 g glucose load) to body weight was assessed. Body weight can be used as an easily-measurable indicator of the efficacy of preventive measures with respect to the above-mentioned coronary risk factors. The data were derived from a study of 6109 males, aged 40-59, carried out within a cooperative multifactorial coronary disease prevention program in Kaunas. The degree of correlation was assessed on the basis of single examinations, and the variation of the levels of the risk factors in question was examined in relation to changes in body weight over a period of time. Quantitative estimates of change in blood pressure and blood cholesterol and glucose levels corresponding to a weight change of 1 kg were obtained.


Analysis of PM2.5 concentrations under pollutant emission control strategies in the metropolitan area of São Paulo, Brazil.
Great efforts have been made over the years to assess the effectiveness of air pollution controls in place in the metropolitan area of São Paulo (MASP), Brazil. In this work, the community multiscale air quality (CMAQ) model was used to evaluate the efficacy of emission control strategies in MASP, considering the spatial and temporal variability of fine particle concentration. Seven different emission scenarios were modeled to assess the relationship between the emission of precursors and ambient aerosol concentration, including a baseline emission inventory, and six sensitivity scenarios with emission reductions in relation to the baseline inventory: a 50% reduction in SO2 emissions; no SO2 emissions; a 50% reduction in SO2, NOx, and NH3 emissions; no sulfate (PSO4) particle emissions; no PSO4 and nitrate (PNO3) particle emissions; and no PNO3 emissions. Results show that ambient PM2.5 behavior is not linearly dependent on the emission of precursors. Variation levels in PM2.5 concentrations did not correspond to the reduction ratios applied to precursor emissions, mainly due to the contribution of organic and elemental carbon, and other secondary organic aerosol species. Reductions in SO2 emissions are less likely to be effective at reducing PM2.5 concentrations at the expected rate in many locations of the MASP. The largest reduction in ambient PM2.5 was obtained with the scenario that considered a reduction in 50% of SO2, NOx, and NH3 emissions (1 to 2 μg/m3 on average). It highlights the importance of considering the role of secondary organic aerosols and black carbon in the design of effective policies for ambient PM2.5 concentration control.


Inhibitory and excitatory muscarinic receptors modulating the release of acetylcholine from the postganglionic parasympathetic neuron of the chicken heart.
The effects of muscarinic receptor antagonists on ACh release were studied in the absence or presence of cholinesterase (ChE) inhibition using the isolated perfused chicken heart. Presynaptic inhibitory muscarinic autoreceptor were characterized by determining the potency of various antagonists to enhance [3H]-ACh release evoked by field stimulation (3 Hz, 1 min). The order of potencies was: (+/-)-telenzepine > atropine > 4-DAMP > silahexocyclium > pirenzepine > hexahydro-siladifenid-ol > AF-DX 116. The comparison with known pA2 values for M1-, M2- and M3-receptors revealed that the presynaptic autoreceptor meets the criteria of an M1-receptor. Basal, not electrically evoked overflow of unlabelled ACh into the perfusate was caused by 'leakage' release (non-exocytotic), as it was independent of extracellular Ca2+. Muscarinic receptor antagonists failed to enhance basel overflow. In contrast, when ChE activity was inhibited by 10(-6) M tacrine or pretreatment with 10(-4) M DFP, the ACh overflow was partially Ca(2+)-dependent and was reduced by tetrodotoxine. Moreover, block of the inhibitory muscarinic autoreceptors by (+/-)-telenzepine or pirenzepine caused a several-fold enhancement of the ACh release. The potencies of these antagonists were identical to those found for the electrically evoked [3H]-ACh release. The rate of ACh release enhanced by ChE inhibition plus telenzepine corresponds to about 12% of the total ACh pool per min, which is about the maximum amount of ACh that is available for any kind of stimuli. The release was dependent on the presence of exogenous choline. Hence elevation of ACh release led to a correspondingly enhanced ACh synthesis.(ABSTRACT TRUNCATED AT 250 WORDS)


The effect of infliximab treatment on insulin resistance in patients with rheumatoid arthritis.
It is well known that increased insulin resistance is associated with the development of cardiovascular disease in patients with rheumatoid arthritis and that tumour necrosis factor-alpha plays an important role in this process. Infliximab is a chimeric monoclonal anti-tumour necrosis factor-alpha antibody. This study investigates the effects of long term infliximab treatment on insulin resistance in patients with rheumatoid arthritis. Seven rheumatoid arthritis patients (6 female and 1 male; mean age: 44.6 +/- 12.3, mean duration of disease: 6.8 y) for whom infliximab treatment had been planned at the rheumatology and internal medicine clinics were included. Patients were evaluated during and at the end of the study with a mean follow-up duration of 9.6 months. Fasting plasma glucose, fasting plasma insulin levels and serum lipid profile were assessed at baseline and throughout the treatment period (prior to every infusion). Homeostasis Model Assessment of Insulin Resistance model was used for the assessment of insulin sensitivity. Fasting insulin and Homeostasis Mode Assessment of Insulin Resistance levels decreased after treatment (from 19.4 +/- 7.7 microU/ml to 8.9 +/- 4.1 microU/ml and from 2.4 +/- 1 to 1.1 +/- 0.5, respectively; p < 0.05 for both). No significant change was observed in other parameters. An improvement in insulin sensitivity was observed in patients receiving long term infliximab treatment for rheumatoid arthritis.


Adults and larvae of Skrjabinocerca canutus n. sp. (Nematoda: Acuariidae) from Calidris canutus rufa (Aves: Scolopacidae) on the southern Southwest Atlantic coast of South America.
Adults and larvae of a new species of Skrjabinocerca Shikhobalova, 1930 (Nematoda: Acuarioidea) are described on the basis of light and scanning electron microscope studies. Specimens were recovered from Calidris canutus rufa Wilson (Aves: Scolopacidae) from the Southwest Atlantic coast of Uruguay. Data on the hosts, localities and main features of the four previously described species of the genus are provided. S. canutus n. sp. can be distinguished its congeners by a combination of the following characters: non-recurrent cordons, shorter right spicule and possession of a delicate finger-like projection on the distal end of the left spicule. S. prima Shikhobalova, 1930 has a left spicule which is stilletto-shaped and sharply pointed, S. europaea Wong & Anderson, 1993 has recurrent cordons, S. americana Wong & Anderson, 1993 possesses two delicate digitiform projections on the distal end of its left spicule and S. bennetti Bartlett & Anderson, 1996 has subequal spicules.


The cellular response to induction of the p21 c-Ha-ras oncoprotein includes stimulation of jun gene expression.
We have studied the effects of c-Ha-ras oncogene in mouse NIH 3T3 fibroblasts by DNA transfection and analysis of gene expression at the mRNA and protein level in a heat- and heavy metal-inducible model system. The human c-Ha-ras proto-oncogene and oncogene were cloned under the hsp70 heat-shock promoter. Clonal lines of cells with negligible basal expression of the hsp-c-Ha-ras oncogene construct were chosen on the basis of the inducibility of p21c-Ha-ras protein and several transformation parameters. We demonstrate that the expression of ornithine decarboxylase (ODC) mRNA is enhanced approximately 4-6 h after the induction of the p21c-Ha-ras oncoprotein. This increase was reversible upon cessation of c-Ha-ras mRNA and protein synthesis, while constitutively elevated ODC was characteristic for stably c-Ha-ras-transformed cells. The high-level expression of ODC in ras-transformed cells was insensitive to tumour promoter stimulation. A similar mRNA induction by c-Ha-rasVal-12 was also observed for two other serum- and tumour promoter-regulated genes associated with the transformed phenotype: transin (stromelysin) and the glucose transporter. This prompted us to examine also potential changes in the expression of the serum- and tumour promoter-induced transcription factor genes junB and c-jun after induction of the hsp--c-Ha-ras construct. The junB mRNA was enhanced approximately 10-fold and the c-jun oncogene mRNA to a lesser degree in the hsp--c-Ha-ras-transfected cells after zinc activation of the hsp70 promoter. These effects were not seen in similarly treated control cells.(ABSTRACT TRUNCATED AT 250 WORDS)


The golden root, Rhodiola rosea, prolongs lifespan but decreases oxidative stress resistance in yeast Saccharomyces cerevisiae.
The effect of aqueous extract from R. rosea root on lifespan and the activity of antioxidant enzymes in budding yeast Saccharomyces cerevisiae have been studied. The supplementation of the growth medium with R. rosea extract decreased survival of exponentially growing S. cerevisiae cells under H(2)O(2)-induced oxidative stress, but increased viability and reproduction success of yeast cells in stationary phase. The extract did not significantly affect catalase activity and decreased SOD activity in chronologically aged yeast population. These results suggest that R. rosea acts as a stressor for S. cerevisiae cells, what sensitizes yeast cells to oxidative stress at exponential phase, but induces adaptation in stationary phase cells demonstrating the positive effect on yeast survival without activation of major antioxidant enzymes.