Why do cotton-top tamarin female helpers carry infants? A preliminary study.
Shortly after giving birth, cotton-top tamarin mothers frequently attack the eldest female helpers [Snowdon et al., American Journal of Primatology 31:11-21, 1993]. Sometimes this aggression leads to the eviction of the eldest daughters from their natal groups 3-4 months after the birth of infants [Price & McGrew, Folia Primatologica 57:16-27, 1991]. We propose that daughters, during the act of carrying infants, may receive less aggression from mothers than when they are not carrying. On the other hand, given that mothers benefit from having others carry their infants, overall aggression received by female helpers from their mothers might be lower in those female helpers with a larger relative contribution to this activity. Four groups were observed during the first 9 weeks following the birth of infants, and aggression received was recorded for symmetrical as well as nonsymmetrical interactions. We found a positive correlation between contribution to infant carrying of female helpers and the overall aggression received from their mothers. Furthermore, the two eldest daughters with highest values of carrying contribution were evicted from their natal groups 3-4 months after the birth of infants. Although mothers do not appear to be more tolerant of female helpers that contribute the most to infant carrying, daughters do benefit from reduced aggression during the act of carrying, and remain in their natal group during the time period when infants must be carried.


Permanent alteration of central noradrenergic system by prenatally administered amphetamine.
Amphetamine-induced psychosis is frequently associated with a chronic, high-dose, daily pattern of amphetamine exposure. In the present study we investigate the effects of prenatal exposure to amphetamine during the development of the central noradrenergic (NA) system in adult rats. Pregnant Wistar rats were given 4 mg/kg/day of d-amphetamine (AMPH), subcutaneously, from gestational day 8 to 21. No additional drug treatment was given to the animals until the beginning of the experiments, in adult, control and prenatally amphetamine treated rats. Since we study the electrophysiology and neurochemistry of the central NA system, we investigated the electric activity of locus coeruleus (LC) norepinephrine (NE) neurons and the levels of NE on prefrontal cortex. What we found, was a decreased number of spontaneously active cells in the LC nucleus with a lower pattern of discharge whereas, the basal levels of NE in the prefrontal cortex, was greatly increased. The increased cortical NE levels, observed in the present study may account for the proposed hyperactive NA system being responsible for some psychotic symptoms observed in paranoid schizophrenia. Besides, our results concerning the permanent alteration observed in the central NA system, in rats prenatally exposed to amphetamine, raise the possibility that this animal model may be useful to further study the neurobiologic alterations underlying certain clinical features involved in some psychosis such as schizophrenia.


[Expression and significance of MMP2 and type IV collagen in gastric cancer].
To evaluate the relationship between the expression of MMP(2), type IV collagen, and invasion and metastasis of gastric cancer. The expression of MMP(2) and Type IV collagen was observed by using immunohistochemistry technique. The MMP(2) expression clearly appeared in the poor-differentiated adenocarcinoma and tubular adenocarcinoma (85.7%, 77.7%). Type IV collagen destruction was observed simultaneously. MMP(2) was highly expressed in patients with cancer embolus in blood vessel and lymphatic vessel or with lymph node metastasis (83.3%, 86.7%). The high expression of MMP(2) was significantly associated with infiltration and metastasis of gastric cancer. The extracellular matrix, especially type IV collagen was destroyed in the cases of high expression of MMP(2). These results suggest that monitoring the level of MMP(2) expression may be an index for evaluation of prognosis.


Partition behaviour of a cultured mouse mammary cancer cell line in aqueous two-phase polymer systems.
Cell surface-associated changes in behaviour of cultured cells on partition in an aqueous two-phase polymer system were studied using FM3A cell line (a cultured mammary cancer of mouse) with respect to aging. The aqueous polymer system consisted of dextran, polyethyleneglycol and sodium phosphate, equilibrated at 6 degrees C to separate into two phases. Enzyme treatment of cells with neuraminidase reduced cell electrophoretic mobility, as well as the cell partition ratio. Hyaluronidase produced no observable effects on partition and cell electrophoretic mobility, suggesting that the partition is related to culture time was similar for both cell electrophoretic mobility and cell partition, showing a rise and fall of charge-associated cell surface change during cell growth, the maxium occurring at the beginning of exponential growth. This change was reflected in the pattern of countercurrent distribution of the cells in respective stages of growth. Countercurrent distribution with our two-phase system is expected to be capable of fractionating cell populations according to cell surface properties.


Association of TUSC1 and DPF3 gene polymorphisms with male infertility.
Recently, genome-wide association studies of a Hutterite population in the USA revealed that five single nucleotide polymorphisms (SNPs) with a significant association with sperm quality and/or function in ethnically diverse men from Chicago were significantly correlated with family size. Of these, three SNPs (rs7867029, rs7174015, and rs12870438) were found to be significantly associated with the risk of azoospermia and/or oligozoospermia in a Japanese population. In this study, we investigated whether the rs10966811 (located in an intergenic region between the TUSC1 and IZUMO3 genes) and rs10129954 (located in the DPF3 gene) SNPs, previously related to family size, are associated with male infertility. In addition, we performed association analysis between rs12348 in TUSC1 and rs2772579 in IZUMO3 and male infertility. We genotyped 145 patients with infertility (including 83 patients with azoospermia and 62 with oligozoospermia) and 713 fertile controls by PCR-RFLP technique for polymorphism. Because rs10966811 has no restriction sites, the SNP rs12376894 with strong linkage disequilibrium was selected as an alternative to rs10966811. There was a statistically significant association between rs12376894 proxy SNP of rs10966811 and oligozoospermia. Also, a statistically significant association between rs10129954 and azoospermia, and oligozoospermia was observed. When we assessed the relationship between rs12348 in TUSC1 and rs2772579 in IZUMO3 and male infertility traits, we found that rs12348 in TUSC1 was significantly associated with azoospermia and oligozoospermia, but rs2772579 in IZUMO3 was not associated with male infertility. We found that the polymorphisms in TUSC1 and DPF3 displayed strong associations with male infertility.


Optimization of digital image processing to determine quantum dots' height and density from atomic force microscopy.
An optimized method of digital image processing to interpret quantum dots' height measurements obtained by atomic force microscopy is presented. The method was developed by combining well-known digital image processing techniques and particle recognition algorithms. The properties of quantum dot structures strongly depend on dots' height, among other features. Determination of their height is sensitive to small variations in their digital image processing parameters, which can generate misleading results. Comparing the results obtained with two image processing techniques - a conventional method and the new method proposed herein - with the data obtained by determining the height of quantum dots one by one within a fixed area, showed that the optimized method leads to more accurate results. Moreover, the log-normal distribution, which is often used to represent natural processes, shows a better fit to the quantum dots' height histogram obtained with the proposed method. Finally, the quantum dots' height obtained were used to calculate the predicted photoluminescence peak energies which were compared with the experimental data. Again, a better match was observed when using the proposed method to evaluate the quantum dots' height.


Single-plaque vegetating bromoderma.
Potassium bromide is still in use for the treatment of multidrug-resistant seizures. It is a known cause of severe drug-induced skin disorders. The clinical presentation of bromoderma may be similar to that of pyoderma gangrenosum when occurring with a single lesion. The case of a young girl with a single vegetating plaque of bromoderma on the leg is reported. The presence of pustules at the periphery of the plaque provides the clinical clue to the diagnosis.


Quantitative proteomics profiling of plasma from children with asthma.
A lack of validated blood diagnostic markers presents an obstacle to asthma control. The present study sought to profile the plasma proteins of children with asthma and to determine potential biomarkers. Plasma samples from children in acute exacerbation (n = 4), in clinical remission (n = 4), and from healthy children (n = 4, control) were analyzed using a tandem mass tag (TMT)-labeling quantitative proteomics and the candidate biomarkers were validated using liquid chromatography-parallel reaction monitoring (PRM)/mass spectrometry (MS) with enzyme-linked immunosorbent assay (ELISA). We identified 347 proteins with differential expression between groups: 125 (50 upregulated, 75 downregulated) between acute exacerbation and control, 142 (72 upregulated, 70 downregulated) between clinical remission and control, and 55 (22 upregulated, 33 downregulated) between acute and remission groups (all between-group fold changes > 1.2; P < 0.05 by Student's t-test). Gene ontology analysis implicated differentially expressed proteins among children with asthma in immune response, the extracellular region, and protein binding. Further, KEGG pathway analysis of differentially expressed proteins identified complement and coagulation cascades and Staphylococcus aureus infection pathways as having the highest protein aggregation. Our analyses of protein interactions identified important node proteins, particularly KRT10. Among 11 differentially expressed proteins, seven proteins (IgHD, IgHG4, AACT, IgHA1, SAA, HBB, and HBA1) were verified through PRM/MS. Protein levels of AACT, IgA, SAA, and HBB were verified through ELISA and may be useful as biomarkers to identify individuals with asthma. In conclusion, our study presents a novel comprehensive analysis of changes in plasma proteins in children with asthma and identifies a panel for accessory diagnosis of pediatric asthma.


Development of lipophilic ester prodrugs of dolutegravir for intestinal lymphatic transport.
The establishment of latent cellular and anatomical viral reservoirs is a major obstacle to achieving a cure for people infected by HIV. Mesenteric lymph nodes (MLNs) are one of the most important anatomical reservoirs of HIV. Suboptimal levels of antiretroviral (ARVs) drugs in these difficult-to-penetrate viral reservoirs is one of the limitations of current antiretroviral therapy (ART) regimens. This study aimed to design and assess highly lipophilic ester prodrugs of dolutegravir (DTG) formulated with long-chain triglyceride (LCT) for delivery of DTG to the viral reservoir in mesenteric lymph and MLNs. A number of alkyl ester prodrugs of DTG were designed based on the predicted affinity to chylomicrons (CM), and the six most promising prodrugs were selected and synthesised. The synthesised prodrugs were further assessed for their intestinal lymphatic transport potential and biotransformation in biorelevant media in vitro and ex vivo. DTG and the most promising prodrug (prodrug 5) were then assessed in pharmacokinetic and biodistribution studies in rats. Although oral administration of 5 mg/kg of unmodified DTG (an allometrically scaled dose from humans) with or without lipids achieved concentrations above protein binding-adjusted IC90 (PA-IC90) (64 ng/mL) in most tissues, the drug was not selectively targeted to MLNs. The combination of lipophilic ester prodrug and LCT-based formulation approach improved the targeting selectivity of DTG to MLNs 4.8-fold compared to unmodified DTG. However, systemic exposure to DTG was limited, most likely due to poor intestinal absorption of the prodrug following oral administration. In vitro lipolysis showed a good correlation between micellar solubilisation of the prodrug and systemic exposure to DTG in rats in vivo. Thus, it is prudent to include in vitro lipolysis in the early assessment of orally administered drugs and prodrugs in lipidic formulations, even when intestinal lymphatic transport is involved in the absorption pathway. Further studies are needed to clarify the underlying mechanisms of low systemic bioavailability of DTG following oral administration of the prodrug and potential ways to overcome this limitation.


Production of the Bacillus licheniformis SubC protease using Lactococcus lactis NICE expression system.
In this work the subC gene from Bacillus licheniformis encoding subtilisin was cloned into the nisin-controlled expression (NICE) vectors (pNZ8048 and pNZ8148) with or without the signal peptide SP Usp45 directing extracellular secretion via Sec machinery. Extracellular protease production and activity was tested using Lactococcus lactis NZ9000 as host, which could be used for rennet production. The efficiency of protein production was tested using purified nisin and the supernatant of L. lactis NZ970 nisin producer. Similar results were obtained for 1 ng/ml nisin and 10 000 diluted supernatant. SP Usp45 signal peptide effectively directed extracellular localization of active and stable protease. SubC signal for extracellular localization in B. licheniformis, was also recognized by L. lactis Sec pathway, although with lower efficiency, as shown by a 3-fold lower protease activity in the medium. Protease production and activity was optimized using parameters such as induction time, nutrients (glucose, casitone) supplementation during growth or protease stabilization by calcium ions. The results were also verified in fed-batch bioreactor for further scale-up of the expression system.


Ecotoxicity studies of two atrazine nanoformulations: From the evaluation of stability in media to the effects on aquatic organisms.
In the field of agriculture, nanopesticides have been developed as an alternative to the conventional pesticides, being more efficient for pest control. However, before their widespread application it is essential to evaluate their safe application and no environmental impacts. In this paper, we evaluated the toxicological effects of two kinds of atrazine nanoformulations (ATZ NPs) in different biological models (Raphidocelis subcapitata, Danio rerio, Lemna minor, Artemia salina, Lactuca sativa and Daphnia magna) and compared the results with nanoparticle stability over time and the presence of natural organic matter (NOM). The systems showed different characteristics for Zein (ATZ NPZ) (184 ± 2 nm with a PDI of 0.28 ± 0.04 and zeta potential of (30.4 ± 0.05 mV) and poly(epsilon-caprolactone (ATZ PCL) (192 ± 3 nm, polydispersity (PDI) of 0.28 ± 0.28 and zeta potential of -18.8 ± 1.2 mV) nanoparticles. The results showed that there is a correlation between nanoparticles stability and the presence of NOM in the medium and Environmental Concentrations (EC) values. The stability loss or an increase in nanoparticle size result in low toxicity for R. subcapitata and L. minor. For D. magna and D. rerio, the presence of NOM in the medium reduces the ecotoxic effects for ATZ NPZ nanoparticles, but not for ATZ NPs, showing that the nanoparticles characteristics and their interaction with NOM can modulate toxic effects. Nanoparticle stability throughout the evaluation must be considered and become an integral part of toxicity protocol guidelines for nanopesticides, to ensure test quality and authentic results regarding nanopesticide effects in target and non-target organisms.


Chitosan-silane sol-gel hybrid thin films with controllable layer thickness and morphology.
The preparation of thin films of chitosan-silane hybrid materials by combining sol-gel processing and spin coating is reported. A variety of silanes can be used as starting materials for the preparation of such thin films, namely tetraethoxysilane, tri-tert-butoxysilanol, trimethylethoxysilane, p-trifluoromethyltetra-fluorophenyltriethoxysilane, trivinylmethoxysilane, (methoxymethyl)trimethyl-silane, and hexamethoxydisilane. These silanes are subjected to a sol-gel process before they are added to acidic chitosan solutions. The chitosan:silane ratio is kept constant at 6:1 (w/w) and dilutions with ethanol are prepared and spin coated. Depending on the degree of dilution, film thickness can be controlled in a range between 5 and 70 nm. For the determination of additional surface properties, static water contact angle measurements and atomic force microscopy have been employed.


Lactobacillus casei DBN023 protects against jejunal mucosal injury in chicks infected with Salmonella pullorum CMCC-533.
Pullorum disease is one of the most serious poultry diseases. Antibiotic prophylaxis is commonly applied in actual production, but the emergence of drug-resistant strains and drug residues threatens the health of animals and humans. The use of probiotics has become a potential solution for the aforementioned problem. In this study, we investigated the effects of Lactobacillus casei DBN023 (CGMCC-16146) on the intestinal tissue structure and immune functions of the jejunal epithelium in chicks infected with Salmonella pullorum CMCC-533 using histomorphological and immunological methods. A total of 450 newborn chicks were randomly divided into the control group and experimental groups. We used hematoxylin and eosin (H&E) staining, immunohistochemistry (IHC), and an enzyme-linked immunosorbent assay (ELISA) to observe the structure of the jejunal mucosa and analyze changes in cytokine and secretory immunoglobulin A (sIgA) levels. The results showed that prophylactic feeding of L. casei DBN023 to chicks significantly increased their jejunum villar height, villar height-to-crypt-depth (V/C) ratio, and muscle thickness; reduced intestinal-crypt depth; and increased the proliferating cell nuclear antigen (PCNA) level compared with S. pullorum infection. L. casei DBN023 enhances intestinal mucosal immunity, regulates cytokine balance, enhances intestinal immune function, and effectively reduces intestinal inflammation. Thus, it protects intestinal tissues and reduces S. pullorum CMCC-533 damage to the intestinal tract.


Indoleamine 2,3-dioxygenase-dependent neurotoxic kynurenine metabolism mediates inflammation-induced deficit in recognition memory.
Cognitive dysfunction in depression is a prevalent and debilitating symptom that is poorly treated by the currently available pharmacotherapies. Research over the past decade has provided evidence for proinflammatory involvement in the neurobiology of depressive disorders and symptoms associated with these disorders, including aspects of memory dysfunction. Recent clinical studies implicate inflammation-related changes in kynurenine metabolism as a potential pathogenic factor in the development of a range of depressive symptoms, including deficits in cognition and memory. Additionally, preclinical work has demonstrated a number of mood-related depressive-like behaviors to be dependent on indoleamine 2,3-dioxygenase-1 (IDO1), the inflammation-induced rate-limiting enzyme of the kynurenine pathway. Here, we demonstrate in a mouse model, that peripheral administration of endotoxin induced a deficit in recognition memory. Mice deficient in IDO were protected from cognitive impairment. Furthermore, endotoxin-induced inflammation increased kynurenine metabolism within the perirhinal/entorhinal cortices, brain regions which have been implicated in recognition memory. A single peripheral injection of kynurenine, the metabolic product of IDO1, was sufficient to induce a deficit in recognition memory in both control and IDO null mice. Finally, kynurenine monooxygenase (KMO) deficient mice were also protected from inflammation-induced deficits on novel object recognition. These data implicate IDO-dependent neurotoxic kynurenine metabolism as a pathogenic factor for cognitive dysfunction in inflammation-induced depressive disorders and a potential novel target for the treatment of these disorders.


Aesthetic and technical strategies for networked music performance.
Networked music is no longer a future genre: the global quarantine event of 2020 launched the concept of performing together over the Internet into the mainstream. While the demand for performing at a distance may be a new imperative, musicians find themselves faced with technological and performative processes that do not appear to be suitable for performing music together online, due particularly to network latency which disrupts the ability for musicians to synchronize. The research presented in this paper investigates and challenges the reasons why networked music is not readily embraced by musicians and describes how that might change, by way of interviews with practitioners and an in-depth review of the technical constraints. Limitations that might cause frustration are in fact shown to have creative strategies that give rise to aesthetic approaches, distinct to the platform. By exploiting the constraints, in tandem with developing technology designed specifically for remote performance, aesthetic implications arise that not only accommodate the inconveniences of latency and acoustic feedback but can help us adapt and transform how we engage in real-time online, towards a future where we can imagine performing together over even more dramatic distances such as high-latency, low-bandwidth locations outside of urban areas-or even over galactic distances.


Molecular mycology: a genetic toolbox for Histoplasma capsulatum.
Research in medical mycology has traditionally been a mix of exciting biology and frustrating genetics, although the excitement has been steadily increasing as genetic obstacles have been successfully overcome. Now, a variety of fungal pathogens can be studied using molecular techniques derived from classical bacterial and yeast genetics, but with selective and strategic adaptations. Histoplasma capsulatum is the best-studied of the primary pathogens known as 'dimorphic' fungi, and tailored molecular genetic strategies are beginning to reveal a repertoire of genes and gene products intimately associated with pathogenesis.


The association of mindfulness with professional quality of life and negative emotional states among critical care nurses during COVID-19 pandemic.
The recent coronavirus disease 2019 (COVID-19) pandemic has imposed severe psychological pressure on nurses. Mindfulness has been shown to be effective in improving professional quality of life (ProQOL) and reducing psychological distress in a wide range of populations and contexts. However, its role in supporting critical care nurses during the outbreak of COVID-19 has yet to be established. This study explores the relationship of mindfulness with negative emotional states and ProQOL among nurses working in critical care units during COVID-19 pandemic. A cross-sectional descriptive correlational design was used. A sample of 156 critical care nurses completed self-reported measures of mindfulness, ProQOL, and negative emotional states. Multiple regressions were used to address the study purpose. Overall, the participants had severe anxiety, moderate depression, moderate stress, moderate burnout, moderate secondary traumatic stress, and moderate compassion satisfaction. Mindfulness was significantly and negatively associated with stress (r = - 0.230, p = .004), depression (r = - 0.190, p = .018), burnout (r = - 0.218, p = .007), and secondary traumatic stress (r = - 0.168, p = .037). Mindfulness explained 3% of the variance in depression (B = -0.19, p = .018), 3.9% of variance in stress, (B = -0.201, p = .012), 4.2% of variance in BO (B = -0.206, p = .009), and 2.2% of the variance in secondary traumatic stress (B = -0.168, t = -2.104, p = .037), controlling for demographics. The current study provides preliminary evidence that mindfulness can be helpful in reducing critical care nurses' psychological distress and promoting their ProQOL, and is worthy of further investigation in this population.


Bio-inspired adhesive porous particles with human MSCs encapsulation for systemic lupus erythematosus treatment.
Mesenchymal stem cells (MSCs) therapy is a promising treatment for Systemic lupus erythematosus (SLE) patients. However, this method is encumbered by suboptimal phenotype of MSCs used in clinical settings, and a short in vivo persistence time. Herein, inspired by the natural microstructure of the sand tower worm nest, we proposed novel adhesive porous particles with human MSCs encapsulation via microfluidic electrospray technology for SLE treatment. The porous microparticles were formed by immediate gelation reaction between sodium alginate (ALG) and poly-d-lysine (PDL), and then sacrificed polyethylene oxide (PEO) to form the pores. The resultant microparticles could protect MSCs from immune cells while maintain their immune modulating functions, and achieve rapid exchange of nutrients from the body. In addition, owing to the electrostatic adsorption and covalent bonding between PDL and tissues, the porous microparticles could adhere to the bowel surfaces tightly after intraperitoneal injection. Through in vivo imaging system (IVIS) methods and in vivo study, it was demonstrated that the MSCs-encapsulated porous adhesive microparticles could significantly increase the cellular half-life, turn activated inflammatory macrophages into an anti-inflammatory profile, and ameliorate disease progression in MRL/lpr mice. Thus, the MSCs-encapsulated porous microparticles showed distinctive functions in chronic SLE treatment, with additional potential to be used in a variety of biomedical applications.


[Purification of coronaviruses from contaminated cattle feces].
A scheme was worked out for the obtaining of purified Corona viruses from fecal extracts, which include: centrifugation in an discontinued gradient of sucrose 20--45 per cent, gel filtration through a Sephadex 4B column, and centrifugation in a linear gradient of sucrose 10--50 per cent. By means of such purification the virions remain morphologically intact in sucrose density of 1.11--1.14 gr/cm3, containing no ballast proteins. As many as five polypeptides are demonstrated in polyacrylamide electrophoresis.


False-Positive Finding on 18F FDG PET/CT: Report of a Rare Case With Xanthogranulomatous Inflammation in the Spinal Epidural Space.
Xanthogranulomatous inflammation in the spinal epidural space is extremely rare. We report a case of a 62-year-old man with a xanthogranulomatous inflammation in the spinal epidural space mistaken for lymphoma because of its avid F FDG uptake on PET/CT. This case emphasizes the need for caution when evaluating a spinal epidural mass using F FDG PET/CT as xanthogranulomatous inflammation can induce a false-positive reading on F-FDG PET/CT.


The effect of nonsteroidal anti-inflammatory drugs on eye pain and migraine headache caused by trochleitis.
Trochleitis has been recognized as one of the causes of eye pain and migraine headaches. This study attempts to investigate the effect of ibuprofen on reducing eye pain and migraine headaches caused by trochleitis. In this before-after clinical trial, out of 1100 clinically examined patients with eye pain and migraine symptoms, 33 patients were diagnosed with having trochleitis and trochleodynia confirmed by orbital magnetic resonance imaging images. Ibuprofen (400 mg/6-8 h) was prescribed to the subjects for 15-30 days. The main outcomes were a reduction in tenderness and pain that were evaluated 2 weeks, a month, and 6 months after the prescription. The data were analyzed by STATA (version 14) and using Wilcoxon and McNemar tests. The results revealed that 28 of the subjects (84.8%) experienced a significant reduction in tenderness 2 weeks after undergoing the treatment (P < 0.001). Standard deviation and average of headache scores before and after the treatment were 7.85 ± 1.75 and 0.64 ± 0.61 based on the visual analog scale. The difference between the pain scores before and after the treatment was statistically significant (P < 0.001). Clinical symptoms such as induration (P < 0.001), photophobia (P < 0.001), upward gaze (P < 0.001), and pain after reading (P < 0.001) were reduced significantly. Six months after the treatment, none of the mentioned symptoms was reported by the subjects. The findings revealed that noninvasive treatment (ibuprofen) has reduced eye pain, tenderness, and migraine headaches caused by trochleitis. What is important to mention is that trochleitis should be diagnosed properly.


Growth hormone modulation of arginine-induced glucagon release: studies of isolated growth hormone deficiency and acromegaly.
Plasma glucagon and insulin responses to L-arginine were compared in normal controls and patients with isolated growth hormone deficiency and acromegaly. Patients with isolated growth hormone deficiency were characterized by high plasma glucagon response and low plasma insulin response, whereas acromegalic patients showed exaggerated plasma glucagon response and almost normal insulin response. These results suggest that growth hormone is probably required for optimum function of the islets, and since hyperglucagonaemia was observed in both growth hormone deficiency and acromegaly, metabolic disturbances stemming from the respective primary diseases may affect glucagon secretion.


[Not Available].
A method for the combined determination of the mycotoxins aflatoxin B1, G1, B2, G2, ochratoxin A and zearalenone in cereals and feed is described. After extraction with acetonitrile/water or methanol/water the cleaning takes place with new combined immunoaffinity clean-up column "AflaOchraZea" by VICAM. When the mycotoxins are determined in different cereals with this new type of clean-up column low detection limits and high recovery rates can be reached similar to those obtained by using separate immunoaffinity clean-up colums for the said mycotoxins.


A 14-day elemental diet is highly effective in normalizing the lactulose breath test.
Treatment of small intestinal bacterial overgrowth is frustrated by the low efficacy of antibiotics. Elemental diets have been shown to reduce enteric flora. In this study, we evaluate the ability of an elemental diet to normalize the lactulose breath test (LBT) in IBS subjects with abnormal breath test findings. Consecutive subjects with IBS and abnormal LBT suggesting the presence of bacterial overgrowth underwent a 2-week exclusive elemental diet. The diet consisted of Vivonex Plus (Novartis Nutrition Corp., Minneapolis, MN) in a quantity based on individual caloric requirement. On day 15 (prior to solid food), subjects returned for a follow-up breath test and those with an abnormal LBT were continued on the diet for an additional 7 days. The ability of an elemental diet to normalize the LBT was determined for days 15 and 21. A chart review was then conducted to evaluate any clinical benefit 1 month later. Of the 93 subjects available for analysis, 74 (80%) had a normal LBT on day 15 of the elemental diet. When those who continued to day 21 were included, five additional patients normalized the breath test (85%). On chart review, subjects who successfully normalized their breath test had a 66.4 +/- 36.1% improvement in bowel symptoms, compared to 11.9 +/- 22.0% in those who failed to normalize (P < 0.001). An elemental diet is highly effective in normalizing an abnormal LBT in IBS subjects, with a concomitant improvement in clinical symptoms.


Is there an epidemic vitamin D deficiency in German orthopaedic patients?
Vitamin D plays an essential role in bone health and muscle function. Some studies have shown a widespread rate of vitamin D deficiency in the general population, but few have reported on the vitamin D status of orthopaedic patients. We investigated (1) the extent of hypovitaminosis D in orthopaedic patients, (2) seasonal variations in vitamin D levels, and (3) possible risk factors for insufficient vitamin D levels. Vitamin D levels in 1119 patients consecutively admitted to an orthopaedic surgery department in 2011 were measured. To investigate the correlation between climate factors and vitamin D levels, the sunshine hours for each month in 2011 were collected by Deutscher Wetterdienst (the German weather service) in the region where most tested patients lived. The prevalence of normal (> 30 ng/mL), insufficient (20-30 ng/mL), and deficient (< 20 ng/mL) 25-hydroxyvitamin D levels was determined. Univariate and multivariate analyses were used to assess risk factors for insufficient vitamin D levels. Overall, 84% of patients had insufficient levels of vitamin D and 60% were vitamin D deficient. Only 15% were in the target range of 30 to 60 ng/mL. The prevalence of low vitamin D levels was greater during winter and months with fewer sunshine hours. Vitamin D levels did not vary according to age, sex, and disease. Individuals with obesity, hypertension, and osteoporosis were more likely to have low vitamin D levels compared with their healthy counterparts. There is an alarmingly high rate of hypovitaminosis D and vitamin D deficiency among orthopaedic patients in this region of Germany, whose latitude (50° N) is approximately the same as those of Vancouver (49°, 15' N) and Paris (48°, 51' N). Given the well-known effects on bone metabolism and muscle health, low vitamin D levels may negatively affect patients. Screening and treating hypovitaminosis D appears to be important in this patient population.


Transpedicular wedge resection osteotomy for the treatment of a kyphotic Andersson lesion-complicating ankylosing spondylitis.
Two cases with a long-standing thoracolumbar kyphosis due to ankylosing spondylitis are presented with a symptomatic localized destructive kyphotic lesion of the spine. Clinical and radiographic findings demonstrated a progressive vertebral and discovertebral kyphotic pseudarthrosis, known as an Andersson lesion, at the L1 and L1-2 level, respectively. Surgical correction and stabilization was performed by an extending transpedicular wedge resection osteotomy to restore spinal stability, to facilitate fracture healing as well as to restore the sagittal balance of the ankylosed spine. To predict the effect of a surgical correction of the Andersson lesion on the sagittal balance, deformity planning was performed preoperatively. The indication for surgery, the surgical technique and the 2 years' clinical results are described. In addition, the difficulties experienced with preoperative deformity planning are evaluated.


Soil chemistry and fertility alterations in response to N application in a semiarid Mediterranean shrubland.
N deposition is currently affecting nutrient cycling in terrestrial ecosystems. We studied the effects of four years of N application (0, 10, 20 and 50 kg N ha(-1) year(-1)+background deposition) on soil chemistry and fertility in a semiarid shrubland in central Spain. Soil pH and nutrient availability fluctuated seasonally. The inorganic-N fraction in soil was dominated by nitrate, as expected in calcareous soils. N application increased inorganic N availability in soil. There was a negative correlation between N application and soil K(+) availability and pH, measured as the % change after four years. Soil N and C storage (evaluated as the % change) slightly increased after four years. Our data suggest that, in the short-term, the seasonality of nutrients overwhelm any chemical alteration related to N deposition. However, the potential implication of continuous N addition on soil chemistry in the long-term is not well understood.


Towards associating negative experiences and recommendations reported by Hajj pilgrims in a mass-scale survey.
The annual Hajj presents diversified negative experiences to millions of pilgrims worldwide. The negative experiences and recommendations to overcome them as per pilgrims' feedback are yet to be analyzed from an aggregated perspective in the literature, which we do in this paper. To do so, first, we perform a large-scale survey (n=988) using our comprehensive questionnaire. Then, we perform both quantitative (e.g., clustering) and qualitative (e.g., thematic) analyses on the survey data. Our quantitative analysis reveals up to seven clusters of negative experiences. Further, going beyond the quantitative analysis, our qualitative analysis reveals 21 types of negative experiences, 20 types of recommendations, and nine themes connecting the negative experiences and recommendations. Accordingly, we reveal associations among the negative experiences and recommendations based on the themes in thematic analysis and present the associations through a tripartite graph. However, we have some limitations in this study, such as fewer female and young participants. In future, we plan to collect more responses from female and young participants and extend our work by analyzing linkages in the tripartite graph by augmenting the edges within the graph with appropriate weights. Overall, the findings of this study are expected to facilitate the prioritization of tasks for the management personnel in charge of the Hajj pilgrimage.


Levodopa improves handwriting and instrumental tasks in previously treated patients with Parkinson's disease.
Motor symptoms in patients with Parkinson's disease may be determined with instrumental tests and rating procedures. Their outcomes reflect the functioning and the impairment of the individual patient when patients are tested off and on dopamine substituting drugs. Objectives were to investigate whether the execution speed of a handwriting task, instrumentally assessed fine motor behavior, and rating scores improve after soluble levodopa application. 38 right-handed patients were taken off their regular drug therapy for at least 12 h before scoring, handwriting, and performance of instrumental devices before and 1 h after 100 mg levodopa intake. The outcomes of all performed procedures improved. The easy-to-perform handwriting task and the instrumental tests demand for fast and precise execution of movement sequences with considerable cognitive load in the domains' attention and concentration. These investigations may serve as additional tools for the testing of the dopaminergic response.


Influence of mesiodens on adjacent teeth and the timing of its safe removal.
To focus on the effects of the presence of mesiodens on adjacent teeth and to investigate the timing of its safe removal. Cone-beam computed tomography examinations, obtained at Okayama University Hospital over a three-year period, were inspected. Data were recorded including the number of mesiodens; associated abnormalities; and the relationship with neighboring structures. Depending on multiple factors, the risk of developing complications due to early extraction of a mesiodens was divided into three categories: high, medium, and low risk. A total of 5,958 cone-beam computed tomography exams were obtained, 460 patients aged 3-85 years were diagnosed with a total of 568 mesiodens, 382 (67.3%) of which were discovered in young patients (age <10 years), and 333 (87.2%) of these were associated with abnormalities. Regarding the risk categories, 11 (1.9%) were considered to be in the high-risk, five (0.9%) in the medium-risk and 552 (97.2%) in the low-risk categories. Moreover, eight out of 11 high-risk mesiodens were extracted and no post-operative complications have been seen. As the results showed that no postoperative complications were seen in all the extracted cases of high-risk mesiodens, this indicates the possibility of safe extraction at an early age which could reduce related future complications.


Does severity of spinal cord injury predict likelihood of suffering chronically from severe depression and anxiety?
Qualitative Survey study. One might assume that those with higher and more complete spinal cord injuries are at higher risk of depression and anxiety. The objective of this study was to assess the association between level and severity of injury with the degree of anxiety and depression in chronic spinal cord injury. Spinal Cord Injury Rehabilitation outpatient clinic. 49 subjects were recruited from our research database. Time from injury ranged from 6 months to 20+ years. Sample included 23 motor complete and 26 motor incomplete participants; of these 24 were people with paraplegia, 25 were people with tetraplegia. They answered HADS, BDI-FS and PHQ-9 questionnaires. Participants were grouped based on time post injury and then were further divided by motor complete (AIS A/B) and incomplete (AIS C/D) and level (tetraplegia cf. paraplegia). Two-sample t-tests were conducted to evaluate the differences in depression and anxiety scores, between individuals with different completeness and injury type. There were no significant differences amongst the groups tested regarding severity of depression and anxiety, however, those with paraplegia or incomplete injuries had higher but not significantly higher average scores for depression and anxiety. We found there were no statistically significant differences in depression and anxiety scores among the groups. These results suggest that all people with SCI may be at similar risk of depression and anxiety, regardless of SCI severity and level.


FAO/WHO GIFT (Global Individual Food consumption data Tool): a global repository for harmonised individual quantitative food consumption studies.
Knowing who eats what, understanding the various eating habits of different population groups, according to the geographical area, is critical to develop evidence-based policies for nutrition and food safety. The FAO/WHO Global Individual Food consumption data Tool (FAO/WHO GIFT) is a novel open-access online platform, hosted by FAO and supported by WHO, providing access to harmonised individual quantitative food consumption (IQFC) data, especially in low- and middle-income countries (LMIC). FAO/WHO GIFT is a growing repository, which will serve as the global FAO/WHO hub to disseminate IQFC microdata. Currently five datasets from LMIC are available for dissemination, and an additional fifty datasets will be made available by 2022. To facilitate the use of these data by policy makers, ready-to-use food-based indicators are provided for an overview of key data according to population segments and food groups. FAO/WHO GIFT also provides an inventory of existing IQFC data worldwide, which currently contains detailed information on 188 surveys conducted in seventy-two countries. In order for end-users to be able to aggregate the available data, all datasets are harmonised with the European Food Safety Authority's food classification and description system FoodEx2 (modified for global use). This harmonisation is aimed at enhancing the consistency and reliability of nutrient intake and dietary exposure assessments. FAO/WHO GIFT is developed in synergy with other global initiatives aimed at increasing the quality, availability and use of IQFC data in LMIC to enable evidence-based decision-making and policy development for better nutrition and food safety.


Anopheles culicifacies sibling species in Odisha, eastern India: First appearance of Anopheles culicifacies E and its vectorial role in malaria transmission.
To identify the Anopheles culicifacies sibling species complex and study their vectorial role in malaria endemic regions of Odisha. Mosquitoes were collected from 6 malaria endemic districts using standard entomological collection methods. An. culicifacies sibling species were identified by multiplex polymerase chain reaction (PCR) using cytochrome oxidase subunit II (COII) region of mitochondrial DNA. Plasmodium falciparum (Pf) sporozoite rate and human blood fed percentage (HBF) were estimated by PCR using Pf- and human-specific primers. Sequencing and phylogenetic analysis were performed to confirm the type of sibling species of An. culicifacies found in Odisha. Multiplex PCR detected An. culicifacies sibling species A, B, C, D and E in the malaria endemic regions of Odisha. An. culicifacies E was detected for the first time in Odisha, which was further confirmed by molecular phylogenetics. Highest sporozoite rate and HBF percentage were observed in An. culicifacies E in comparison with other sibling species. An. culicifacies E collected from Nawarangapur, Nuapara and Keonjhar district showed high HBF percentage and sporozoite rates. An. culicifacies B was the most abundant species, followed by An. culicifacies C and E. High sporozoite rate and HBF of An. culicifacies E indicated that it plays an important role in malaria transmission in Odisha. Appropriate control measures against An. culicifacies E at an early stage are needed to prevent further malaria transmission in Odisha.


Diminished confidence in prospective memory causes doubts and urges to check.
Correlational research has demonstrated links between prospective memory and checking compulsions. These findings suggest that negative beliefs and diminished confidence in prospective memory may contribute to intrusive doubts that tasks were not completed and ultimately to checking behavior. The present study represents the first experimental test of the hypothesis that diminished confidence in prospective memory causes increased doubt and urges to check. Participants completed several tests and questionnaires assessing prospective memory. Participants were randomly assigned to receive either false positive or false negative feedback about their prospective memory. They subsequently completed additional prospective memory tests and their doubts and urges to check that each of those tests was properly performed were assessed. Participants who received false negative feedback about their prospective memory reported significantly higher levels of doubt and urges to check compared to those who received false positive feedback. A non-clinical sample was used and participants with severe levels of depression and anxiety were excused before the feedback phase to avoid causing them further distress. The results provide further support for memory confidence models of checking compulsions by indicating that diminished confidence in prospective memory can cause increased doubt and urges to check.


Secretory activity of the subcommissural organ in Rana temporaria under osmotic stimulation.
The secretory activity of the subcommissural organ (SCO) in the frog Rana temporaria was studied under conditions of dehydration. After injection of a radioactive precursor the amount and concentration of radioactively labelled material in the SCO are smaller in dehydrated than in control animals. Concomitantly, the growth rate of the CSF-fibre (Reissner's fibre) increases in dehydrated animals. It follows that water deprivation enhances the secretory activity of the SCO. To investigate whether the SCO may be responsible for the secretion of an aldosteronotropic factor as suggested in the literature, brains were incubated in vitro with a radioactive precursor and with or without aldosterone. The SCO of the aldosterone-treated brains contains more radioactively labelled material than the SCO of the control brains. It is argued that this is indicative of a lower secretory activity It means that aldosterone inhibits the secretory activity of the SCO, possibly by a process of negative feed-back regulation. The results of the present experiments can be interpreted in favour of an involvement of the SCO-Reissner's fibre complex in osmoregulation.


A purification procedure for the isolation of homogeneous preparations of bovine aorta amine oxidase and a study of its lysyl oxidase activity.
It has been reported that bovine aorta amine oxidase oxidizes lysine residues in tropoelastin to allysine (Rucker, R.B. and O'Dell, B.L. (1971) Biochim. Biophys. Acta 235, 32-43). Pure bovine aorta amine oxidase was isolate by DEAE-cellulose, hydroxylapatite, Bio-Gel A-1.5 m and concanavalin A-Sepharose 4B chromatography. Enzymatic, chromatographic and immunochemical tests disclosed that pure bovine aorta amine oxidase was not a lysyl oxidase capable of oxidizing the lysine residues of tropoelastin to allysine; The bovine aorta amine oxidase preparation used by Rucker and O'Dell appears to have been contaminated with lysyl oxidase which is the emzyme that oxidizes some of the lysine residues in tropoelastin and tropocollagen to allysine.


Quantitative phosphoproteomics reveals the effect of baeSR and acrB genes on protein phosphorylation in Salmonella enterica serovar typhimurium.
The BaeSR two-component system and the AcrB efflux pump are closely associated with Salmonella resistance to antibiotics. However, the relationship between the two-component system, efflux pumps and protein phosphorylation of Salmonella is poorly understood. In this study, Salmonella typhimurium ciprofloxacin-resistant strain CR, baeSR gene deletion strain CRΔbaeSR, acrB gene deletion strain CRΔacrB, and double gene deletion strain CRΔbaeSRΔacrB were used to explore phosphorylated proteins with significant difference, based on non-marker, quantitative phosphorylation modified proteomics technique. Consequently, 363 phosphosites of 213 phosphoproteins were identified in the four strains. More than 70% of the phosphosites were serine phosphorylation. In the CRΔbaeSR/CR, CRΔacrB/CR and CRΔbaeSRΔacrB/CR comparison groups, 36, 37 and 49 phosphosites were significantly altered, respectively. Bioinformatic analysis revealed that the main enrichment pathways of these differentially phosphorylated proteins were metabolic pathways, biosynthesis of antibiotics, phosphotransferase system (PTS), ABC transporters, and lipopolysaccharide biosynthesis. Furthermore, 21 differentially phosphorylated proteins were identified to be associated with antibiotic resistance. These results suggest that the BaeSR two-component system and the AcrB efflux pump affect the phosphorylation of proteins in S. typhimurium and may influence the drug resistance and virulence of S. typhimurium by affecting protein phosphorylation, providing a new idea to explore the mechanism of drug resistance in Salmonella.


Prenatal exposure to bisphenol A and neonatal health outcomes: A systematic review.
Bisphenol A (BPA) is an endocrine-disrupting chemical substance responsible for the composition of polycarbonate plastics and epoxy resins. Early life and pregnancy are important windows of susceptibility. This review aimed to conduct a systematic assessment of human studies to comprehensively describe the association between prenatal BPA exposure and neonatal health outcomes. Literature was searched in Cochrane Library, Embase, PubMed, Scopus, and Web of Science published before November 2022, and were selected according to clear inclusion and exclusion criteria. The Newcastle-Ottawa scale (NOS) and Grades of Recommendation, Assessment, Development, and Evaluation guidelines (GRADE) were followed to grade the methodological quality of studies and the certainty of the evidence respectively. As a result, a total of 22259 participants from 45 trials were included. And the potential associations of prenatal exposure to BPA and neonatal health outcomes were mainly shown in four aspects: gestational age/preterm birth, physical health at birth, the incidence of systemic abnormalities or diseases, and other health outcomes. Although the certainty of the evidence was low to very low, the methodological quality of the included studies was high. Prenatal BPA exposure tended to have negative effects on most of the health outcomes in neonates but showed inconsistent results on physical health at birth. This systematic review is the first to comprehensively synthesize the existing evidence on the association between prenatal BPA exposure and neonatal health outcomes. In the future, further studies are still needed to verify these effects and elucidate the underlying mechanisms.


Persistent developmental stuttering as a cortical-subcortical dysfunction: evidence from muscle activation.
One contemporary view of stuttering posits that speech disfluencies arise from anomalous speech motor control. To verify the rest muscle tension and speech reaction time of fluent and stuttering adults. 22 adults, divided in two groups: G1--11 fluent individuals; G2--11 stutterers. Electromyography recordings (inferior orbicularis oris) were collected in two different situations: during rest and in a reaction time activity. The groups were significantly different considering rest muscle tension (G2 higher recordings) and did not differ when considering speech reaction time and muscle activity during speech. There was a strong positive correlation between speech reaction time and speech muscle activity for G2--the longer the speech reaction time, the higher the muscle activity during speech. In addition to perceptible episodes of speech disfluency, stutterers exhibit anomalies in speech motor output during fluent speech. Correlations with a possible cortical-subcortical disorder are discussed.


Treatment of gastric cancer, with special reference to the survivals of the cancer patients treated with multiple combination MFC therapy or immunochemotherapy of MFC plus OK-432 (NSC B116209).
Investigations were made on the survivals of 81 patients with advanced gastric cancer. Of these, 55 patients were treated with a combination chemotherapy of mitomycin C, 5-fluorouracil, and cytosine arabinoside (i.e., MFC therapy). Another 26 cases were treated with immunochemotherapy of MFC plus OK-432, an immunotherapeutic agent. Fifty percent survival times were 5.4 months for the MFC group, and 7.5 months for the MFC plus OK-432 group. One year survival rates of each group were 13 and 35 percent, respectively. The two year survival was null for the MFC group, and 13 percent for the MFC plus OK-432 group. Statistical analysis revealed that the survival curve of the MFC plus OK-432 decreased more slowly as compared with that of the MFC (p less than 0.05). In other words, the patients treated with MFC plus OK-432 showed a significantly longer survivals compared to the patients treated with MFC alone. Some cases were also presented for the better understanding of the immunochemotherapy of MFC plus OK-432.


Ultrafast B1 mapping with RF-prepared 3D FLASH acquisition: Correcting the bias due to T1 -induced k-space filtering effect.
The traditional radiofrequency (RF)-prepared B1 mapping technique consists of one scan with an RF preparation module for flip angle-encoding and a second scan without this module for normalizing. To reduce the T1 -induced k-space filtering effect, this method is limited to 2D FLASH acquisition with a two-parameter method. A novel 3D RF-prepared three-parameter method for ultrafast B1 -mapping is proposed to correct the T1 -induced quantification bias. The point spread function analysis of FLASH shows that the prepared longitudinal magnetization before the FLASH acquisition and the image signal obeys a linear (not proportional) relationship. The intercept of the linear function causes the quantification bias and can be captured by a third saturated scan. Using the 2D double-angle method (DAM) as the reference, a 3D RF-prepared three-parameter protocol with 9 s duration was compared with the two-parameter method, as well as the saturated DAM (SDAM) method, the dual refocusing echo acquisition mode (DREAM) method, and the actual flip-angle imaging (AFI) method, for B1 mapping of brain, breast, and abdomen with different orientations and shim settings at 3T. The 3D RF-prepared three-parameter method with complex-subtraction delivered consistently lower RMS error, error mean, error standard deviation, and higher concordance correlation coefficients values than the two-parameter method, the three-parameter method with magnitude-subtraction, the multi-slice DREAM and the 3D AFI, and were close to the results of 2D or multi-slice SDAM. The proposed ultrafast 3D RF-prepared three-parameter method with complex-subtraction was demonstrated with high accuracy for B1 mapping of brain, breast, and abdomen.


Mosquito abundance and behavior in the influence area of the hydroelectric complex on the Madeira River, Western Amazon, Brazil.
Malaria is currently highly prevalent and restricted to the north of Brazil, and its dynamics are severely affected by human environmental changes, such as the large dam construction recently approved by the Brazilian Government in Rondônia. We studied the mosquito fauna and behavior before hydroelectric construction. Mosquitoes were captured by human landing catches on the riversides of the Madeira River in Porto Velho, Rondônia. A total of 3121 mosquitoes from eight different genera were collected; only Mansonia and Anopheles darlingi were found in all 21 collection sites throughout the night. These results suggest that the riverines of the study area are exposed to malaria.


Recurrent laryngeal nerve pathology in spasmodic dysphonia.
Since it was first described in 1871, spasmodic (spastic) dysphonia has been considered a disease of psychogenic origin. Unsupported theories of possible organic etiology have appeared sporadically in the literature. In 1976 sectioning of the recurrent laryngeal nerve for patients with this disease was reported with resultant improvement in voice production. This was attempted because the spasmodic dysphonic has, in effect, already compensated vocal cords bilaterally. It was reasoned, therefore, that if one of these was paralyzed the patient would immediately be converted to a state approximating that of well-compensated unilateral vocal cord paralysis which situation, as is well known, usually carries with it a fairly good voice. A controlled study to evaluate the efficacy of this surgical approach has been undertaken at the Cleveland Clinic during the past year. In an attempt to elucidate the possible organic etiology of spasmodic dysphonia, a section of nerve was removed in every case and examined by both light and electron microscopy. Special stains for myelin were also used on the light microscopy specimens. Demyelinization has been found in most of the cases examined by electron microscopy. Possible correlation between this disease entity and other cranial nerve syndromes of unknown etiology is noted. Such conditions as trigeminal neuralgia, glossopharyngeal neuralgia, belpharospasm, hemifacial spasm, and even possibly Bell's palsy may exhibit a similar etiology.


Novel candidate genes for alcoholism--transcriptomic analysis of prefrontal medial cortex, hippocampus and nucleus accumbens of Warsaw alcohol-preferring and non-preferring rats.
Animal models provide opportunity to study neurobiological aspects of human alcoholism. Changes in gene expression have been implicated in mediating brain functions, including reward system and addiction. The current study aimed to identify genes that may underlie differential ethanol preference in Warsaw High Preferring (WHP) and Warsaw Low Preferring (WLP) rats. Microarray analysis comparing gene expression in nucleus accumbens (NAc), hippocampus (HP) and medial prefrontal cortex (mPFC) was performed in male WHP and WLP rats bred for differences in ethanol preference. Differential and stable between biological repeats expression of 345, 254 and 129 transcripts in NAc, HP and mPFC was detected. Identified genes and processes included known mediators of ethanol response (Mx2, Fam111a, Itpr1, Gabra4, Agtr1a, LTP/LTD, renin-angiotensin signaling pathway), toxicity (Sult1c2a, Ces1, inflammatory response), as well as genes involved in regulation of important addiction-related brain systems such as dopamine, tachykinin or acetylcholine (Gng7, Tac4, Slc5a7). The identified candidate genes may underlie differential ethanol preference in an animal model of alcoholism. Names of genes are written in italics, while names of proteins are written in standard font. Names of human genes/proteins are written in all capital letters. Names of rodent genes/proteins are written in capital letter followed by small letters.


Dehydroepiandrosterone (DHEA) ameliorates the insulin sensitivity in older rats.
To evaluate whether dehydroepiandrosterone (DHEA) ameliorates the decreased insulin sensitivity in older rats, hyperinsulinemic euglycemic clamp studies were performed in rats of various age groups previously treated with DHEA. The glucose metabolic clearance rate (MCR) of the control rats showed a gradual decline with the advancing ages (MCR = 13.05 - 0.027*age (days), r2=0.683, p < 0.01, n = 18). The glucose MCR of the DHEA-treated rats also showed a gradual decline with the aging process (MCR = 12.67 - 0.011*age (days), r2=0.429, p < 0.01, n = 18). However, the MCR of the DHEA-treated rats were significantly higher than that of control rats. As glucose MCR is a parameter which indicates the insulin sensitivity in various tissues, especially in muscles and body composition, was not changed after the injection of DHEA, DHEA is considered to work on muscles to increase insulin sensitivity.


Electrophoretic behavior of DNA-methyl-CpG-binding domain protein complexes revealed by capillary electrophoreses laser-induced fluorescence.
The free solution electrophoretic behavior of DNA-protein complexes depends on their charge and mass in a certain experimental condition, which are two fundamental properties of DNA-protein complexes in free solution. Here, we used CE LIF to study the free solution behavior of DNA-methyl-CpG-binding domain protein (MBD2b) complexes through exploring the relationship between the mobilities, charge, and mass of DNA-protein complexes. This method is based on the effective separation of free DNA and DNA-protein complexes because of their different electrophoretic mobility in a certain electric field. In order to avoid protein adsorption, a polyacrylamide-coated capillary was used. Based on the evaluation of the electrophoretic behavior of formed DNA-MBD2b complexes, we found that the values of (μ0 /μ)-1 were directly proportional to the charge-to-mass ratios of formed complexes, where the μ0 and μ are the mobility of free DNA probe and DNA-protein complex, respectively. The models were further validated by the complex mobilities of protein with various lengths of DNA probes. The deviation of experimental and calculated charge-to-mass ratios of formed complexes from the theoretical data was less than 10%, suggesting that our models are useful to analyze the DNA-binding properties of the purified MBD2b protein and help to analyze other DNA-protein complexes. Additionally, this study enhances the understanding of the influence of the charge-to-mass ratios of formed DNA-protein complexes on their separation and electrophoretic behaviors.


Public knowledge, attitude, and practice regarding antibiotics use in Punjab, Pakistan: a cross-sectional study.
Public awareness about antibiotics use is critical in antimicrobial resistance. We evaluated knowledge, attitudes, and practices among the general population of Punjab, Pakistan in this cross-sectional study. We used a 50-item questionnaire to collect information on participant demographics, knowledge, and attitudes about antibiotics use and to evaluate the practices of taking antibiotics without a doctor's prescription. Of the 2106 participants who completed surveys, 35.4% thought antibiotics could cure viral infections; 47.5% believed they are effective against cold and flu. Nearly 60% percent of respondents had self-medicated with antibiotics. Married people (adjusted odds ratio (AOR) = 1.285, 95% confidence interval (CI): 1.004-1.643 p = 0.046), higher antibiotics use knowledge (AOR = 0.818, 95% CI: 0.674-0.993 p = 0.042), ever purchased antibiotics without a physician's prescription (AOR = 2.024 95% CI: 1.674-2.457 p ≤ 0.001) and storing antibiotics at home (AOR = 0.801 95% CI: 0.652-0.985 p = 0.035) were significantly associated with self-medication practices. A high proportion of inappropriate antibiotics use exists among the general population of Punjab. Interventions are needed to improve health literacy and supervise antibiotics sales in retail pharmacies.


Fire, fungi, and beetle influences on a lodgepole pine ecosystem of south-central Oregon.
Interactions between fire, fungi, bark beetles and lodgepole pines growing on the pumice plateau of central Oregon are described. Mountain pine beetle (Dendroctonus ponderosae) outbreaks occur mainly in forests that are 80-150 years old with a mean diameter of about 25 cm and weakened by a fungus, Phaeolus schweinitzii. The outbreak subsides after most of the large diameter trees are killed. The dead trees fuel subsequent fires which return nutrients to the soil, and a new age class begins. The surviving fire scarred trees are prone to infection by the slow fungal disease and about 100 years later these trees are then susceptible to bark beetle attack.


The prediction of common bile duct stones using a neural network.
The role of preoperative ERCP and endoscopic sphincterotomy (ES) in the diagnosis and treatment of suspected common bile duct stones (CBDS) in the laparoscopic age is controversial. The preoperative diagnosis of CBDS by ERCP and the removal of CBDS by ES are advantageous because of technical difficulties in performing laparoscopic exploration of the common bile duct. Approximately 50% of preoperative ERCP examinations are normal, however. The noninvasive diagnosis of CBDS has assumed new importance, but it has proved to be an elusive goal. Neural networks are a form of artificial computer intelligence that have been used successfully to interpret ECGs and to diagnose myocardial infarcts. The purpose of this study was to determine whether a neural network could be trained to predict CBDS accurately in patients at high risk of having duct stones. We trained a back-propagation neural network to predict the presence of CBDS. Retrospective data from patients who had a cholecystectomy and either a preoperative ERCP or intraoperative cholangiogram were used to build the network, and it was tested using unseen data. One hundred forty patients were used to train the network, and 16 patients were used to test it. The trained network was able to predict CBDS in 100% of the patients in both the training and test sets. Screening of high-risk patients for CBDS by neural network analysis is highly accurate. This promising new, noninvasive, and inexpensive technique can potentially decrease the need for preoperative ERCP by 50%, but additional prospective evaluation is indicated.


Calcium currents elicited by voltage steps and steady voltages in myocytes isolated from the rat basilar artery.
1. Whole-cell patch clamp methods were used to record Ca2+ channel currents from isolated rat basilar arterial myocytes either in response to voltage steps or at steady holding potentials. Inward currents were rapidly and reversibly blocked by 2 mM Co2+, and this solution was routinely used to subtract leakage currents. 2. Peak currents measured in response to voltage steps were -85 +/- 23 pA (n = 7) in physiological Ca2+ (1.8 mM) and -256 +/- 39 pA (n = 19) in 10 mM Ba2+. The time course of activation and inactivation were unaffected by changing the holding potential from -88 to -48 mV, and thus we found no evidence for a component of current flowing through transient Ca2+ channels. 3. Activation curves were constructed by dividing the macroscopic current by the single Ca2+ channel current. The product of the number of functional channels and the open-state probability (NPo) measured in this way rose to around 2000. Its dependence on voltage was fitted by a Boltzmann function with half-activation at -8.6 mV in physiological Ca2+ concentrations and a steepness factor in the range 6-8 mV. 4. In physiological solution, block by external Mg2+ reduced peak current through Ca2+ channels by 17%. 5. Steady-state currents were measured by holding the cell at a fixed voltage and rapidly applying Co2+ to block the current through Ca2+ channels. Steady-state currents could be detected at voltages as negative as -58 mV, and persisted for more than 15 min, suggesting that Ca2+ channels in this artery may provide a steady-state Ca2+ influx that contributes to resting contractile tone.


Trace metal accumulation in seagrass and saltmarsh ecosystems of India: comparative assessment and bioindicator potential.
Coastal macrophytes serve as bioindicators of coastal trace metal contamination. In this study, trace metal levels in India's seagrass and saltmarsh ecosystems were assessed for their suitability as bioindicators of metal contamination. Trace metal accumulation and bioindicator potential of both seagrasses and saltmarshes were found to be metal and species-specific. Higher concentrations of Cu, Fe, Mg and Mn were found in the tissues of seagrasses, while saltmarshes showed higher accumulation of Cd, Cr, Hg, Ni, Pb and Zn. The leaves of seagrasses are suitable bioindicator of metals in the water column, while the roots and rhizomes of saltmarshes/seagrasses are suitable bioindicators of metals in the sediment. This study proposes the development of a monitoring network using seagrasses and saltmarss as model organisms for short and long-term monitoring of coastal metal contamination. Determining the phytotoxic levels of trace metals in seagrasses and saltmarsh is important for monitoring plant die-offs and loss.


Applying machine learning methods to psychosocial screening data to improve identification of prenatal depression: Implications for clinical practice and research.
We utilized machine learning (ML) methods on data from the PROMOTE, a novel psychosocial screening tool, to quantify risk for prenatal depression for individual patients and identify contributing factors that impart greater risk for depression. Random forest algorithms were used to predict likelihood for being at high risk for prenatal depression (Edinburgh Postnatal Depression Scale; EPDS ≥ 13 and/or positive self-injury item) using data from 1715 patients who completed the PROMOTE. Performance matrices were calculated to assess the ability of the PROMOTE to accurately classify patients. Probability for depression was calculated for individual patients. Finally, recursive feature elimination was used to evaluate the importance of each PROMOTE item in the classification of depression risk. PROMOTE data were successfully used to predict depression with acceptable performance matrices (accuracy = 0.80; sensitivity = 0.75; specificity = 0.81; positive predictive value = 0.79; negative predictive value = 0.97). Perceived stress, emotional problems, family support, age, major life events, partner support, unplanned pregnancy, current employment, lifetime abuse, and financial state were the most important PROMOTE items in the classification of depression risk. Results affirm the value of the PROMOTE as a psychosocial screening tool for prenatal depression and the benefit of using it in conjunction with ML methods. Using such methods can help detect underreported outcomes and identify what in patients' lives makes them more vulnerable, thus paving the way for effective individually tailored precision medicine.


Relaxing fish-mouth incision for a tight coupler anastomosis.
The microvascular coupler device has reduced operative times and increased patency rates. Attempting to place a smaller tightly fitting vessel around a larger coupler ring can tear vessels and may require substitution with a smaller coupler device, which can not only add additional cost but also compromise the flap. We describe the theoretic and clinical aspects of the 'fish-mouthing' technique that we employ to help with the discrepancy in size of a smaller vessel compared to the coupler ring. The technique involves a longitudinal fish-mouth opening incision into the vessel lumen, prior to impaling the vessels' last three pins on the coupler ring creates two wings and increases the absolute vessel circumference to ease anastomosis .


Inhibition by inorganic ions of a sustained calcium signal evoked by activation of mGlu5 receptors in rat cortical neurons and glia.
The effect of mGlu receptor agonists on intracellular calcium (Ca2+) in rat cortical neurons and glial cells was studied. The responses evoked consisted of two phases; an initial transient response followed by a sustained plateau. In both cell types the order of potency of group I mGlu receptor agonists was DHPG > 1S,3R ACPD > 3-HPG. The selective mGlu5 agonist CHPG elicited responses in both cell types as did S4C3-HPG which is thought to be an mGlu5 agonist at high concentrations. S4-CPG had no effect on intracellular Ca2+ levels nor did it inhibit the action of IS,3R ACPD. These results suggest that the responses in both cell types are mediated by mGlu5 receptors. In the absence of extracellular Ca2+ ions, 1S,3R ACPD (100 microM) induced only a transient Ca2+ response which decayed to baseline with a time constant of approximately 20 s in both cell types. Subsequent readdition of Ca2+ (2 mM) to the external solution in the continued presence of 1S,3R ACPD induced a sustained Ca2+ plateau. The sustained Ca2+ plateau could be blocked by a number of inorganic cations, with an order of potency of Zn2+ > or = La3+ > Cd2+ > or = Co2+ > Ni2+ > Mg2+. Similar concentrations of Zn2+ had little effect on Ca2+-influx evoked by 25 mM K+. It is concluded that the Ca2+-entry pathway activated by mGlu5 receptors resembles store-operated Ca2+-entry pathways that have been described in other cell types.


Allergy and immunology of the aging lung.
The aging process is associated with progressively impaired immune surveillance and decreased ability to mount an appropriate immune response, which potentially leads to increased susceptibility to respiratory insults. In older patients, pneumonias rank high as a reason for hospitalization and cause significant morbidity and mortality. Currently, little is known about how the innate and adaptive immune responses change in the aged human lung or how the changes are linked to increasing susceptibility to respiratory disease. This article reviews the basics of pulmonary host defense and some recently published research on the immune response within the aging lung.


Thrombolysis vs. bleeding from hemostatic sites by a prourokinase mutant compared with tissue plasminogen activator.
A single site mutant (M5) of prourokinase (proUK) was developed to make proUK less vulnerable to spontaneous activation in plasma. This was a problem that seriously compromised proUK in clinical trials, as it precluded proUK-mediated fibrinolysis at therapeutic concentrations. After completing dose-finding studies, 12 anesthetized dogs with femoral artery thrombosis were given either M5 (2.0 mg kg(-1)) or tissue plasminogen activator (t-PA) (1.4 mg kg(-1)) by i.v. infusion over 60 min (20% administered as a bolus). Two pairs of standardized injuries were inflicted at which hemostasis was completed prior to drug administration. Blood loss was quantified by measuring the hemoglobin in blood absorbed from these sites. Thrombolysis was evaluated at 90 min and was comparably effective by both activators. Rethrombosis developed in one t-PA dog. The principal difference found was that blood loss was 10-fold higher with t-PA (mean approximately 40 mL) than with M5 (mean approximately 4 mL) (P = 0.026) and occurred at more multiple sites (mean 2.7 vs. 1.2). This effect was postulated to be related to differences in the mechanism of plasminogen activation by t-PA and M5 in which the latter is promoted by degraded rather than intact (hemostatic) fibrin. In addition, two-chain M5 was efficiently inactivated by plasma C1 inactivator, an exceptional property which helped contain its non-specific proteolytic effect. Intravascular thrombolysis by M5 was accompanied by significantly less bleeding from hemostatic sites than by t-PA. This was attributed to the proUK paradigm of fibrinolysis being retained at therapeutic concentrations by the mutation.


The clinical efficacy of left atrial appendage isolation caused by extensive left atrial anterior wall ablation in patients with atrial fibrillation.
The left atrial appendage (LAA) can be a source of atrial fibrillation (AF) triggering or a part of reentry. We sought to determine the characteristics and clinical outcomes of patients with LAA potential delay including electrical isolation (LAAEI) following LA anterior wall (LAAW) ablation for AF. LAAW ablation cases were collected from among 846 patients who underwent catheter ablation (CA). A total of 89 patients were enrolled; they were divided into three groups according to the extent of LAA potential injury. The ejection fractions (EFs) of the LAA and LA were measured by means of LA angiograms. The mean age of all patients was 56.2 ± 10.7 years (74 males, 83 %). In 47 of the 89 patients, an LAA potential delay was identified after LAAW ablation (group 2). LAAEI was seen in 18 patients (group 3). In the remaining 24 patients, there was no LAA potential delay or LAAEI (group 1). The mean EF decreased significantly after CA in group 3 (P < 0.001). At 21-month follow-up, three patients (17 %) in group 3 had recurrence compared with 11 (42 %) in group 2 and 12 (46 %) in group 3 (P = 0.028). In multivariate analysis, diabetes mellitus and LAA potential delay were independent predictors of AF recurrence (P = 0.021, P = 0.008, respectively). Ablation of the LA anterior wall near the insertion of Bachmann's bundle and the neck of the LAA resulting in LAA potential delay or electrical isolation is effective in preventing recurrence of atrial fibrillation.


Bifunctional g-C3N4/carbon nanotubes/WO3 ternary nanohybrids for photocatalytic energy and environmental applications.
Ternary nanohybrids based on mesoporous graphitic carbon nitride (g-C3N4) were synthesized and presented for developing stable and efficient Hydrogen (H2) production system. Based on photocatalytic activity, optimization was performed in three different stages to develop carbon nanotubes (CNTs) and WO3 loaded g-C3N4 (CWG-3). Initially, the effect of exfoliation was investigated, and a maximum specific surface area of 100.77 m2/g was achieved. 2D-2D interface between WO3 and g-C3N4 was targeted and achieved, to construct a highly efficient direct Z-scheme heterojunction. Optimized binary composite holds the enhanced activity of about 2.6 folds of H2 generation rates than the thermally exfoliated g-C3N4. Further, CNT loading towards binary composite in an optimized weight ratio enhances the activity by 6.86 folds than the pristine g-C3N4. Notably, optimized ternary nanohybrid generates 15,918 μmol h-1. g-1cat of molecular H2, under natural solar light irradiation with 5 vol% TEOA as a sacrificial agent. Constructive enhancements deliver remarkable H2 production and dye degradation activities. Results evident that, the same system can be useful for pilot-scale energy generation and other photocatalytic applications as well.


On the solution of equations for feel-better hemodialysis.
In this paper, a scheme for "feel better" or optimal hemodialysis (OPTHD) based on a two-compartmental model has been proposed. Contrary to the conventional constant blood flow dialysis (CVTHD), this scheme suggests that the blood flow rate should vary in stages in order to avoid or minimize the disequilibrium syndromes during dialysis. A set of equations for computing the intracellular and extracellular solute concentrations during the OPTHD operation is developed and the computed results are illustrated. Comparing to the CVTHD, the OPTHD has the advantages of operating at a lower and smoother solute concentration difference between compartments for the same length of dialysis time, or it may achieve the same specific degree of blood cleansing within a shorter period of dialysis time.


Safety, Efficacy, and Preventive Role of Subcutaneous and Sublingual Allergen Immunotherapy for the Treatment of Pediatric Asthma.
Allergen-specific immunotherapy is currently the only treatment with the potential to modify and prevent progression of allergic asthma in children. In clinical practice, it is available in two forms: subcutaneous immunotherapy and sublingual immunotherapy. Trials and meta-analyses showed both the safety and the short- and long-term benefits of allergen-specific immunotherapy in asthmatic children. However, its use and role in asthma remains controversial, since studies are largely heterogeneous. This is mainly due to the lack of consensus on the optimal primary outcome to be considered for clinical trials evaluating the efficacy of allergen-specific immunotherapy in asthma. Therefore, well-conducted researchis needed using standardized and validated tools to evaluate key outcomes in asthmatic children.


Heritability and genetic correlation of measurements derived from acoustic resonance frequency analysis; a novel method of determining eggshell quality in domestic hens.
Cracked eggshells result in economic loss and provide a route for pathogenic organisms to enter the egg. Genetic factors that contribute to shell strength are likely to decrease the risk that an egg will crack when subject to insult. A novel measurement, the dynamic stiffness of the eggshell (Kdyn) was examined to determine if it might be used in the genetic selection of hens with improved eggshell characteristics. The measurement is determined from acoustic resonance frequency analysis. The estimates of heritability for the novel measurement of Kdyn were moderately high and ranged from 0.33 to 0.53 depending on the model used for the estimation. The estimates of genetic correlation of Kdyn with eggshell breaking strength (0.49) and static stiffness (0.57) were positive and relatively large as expected. There was a small negative genetic correlation between Kdyn and egg production from 26 to 50 weeks of age (-0.19) and a moderate one from 58 to 74 weeks of age (-0.36). The moderate heritability and relative independence of Kdyn indicates that this measurement could be used successfully in a breeding programme to improve shell quality and to reduce the incidence of cracks.


Exogenous proline mitigates toxic effects of cadmium via the decrease of cadmium accumulation and reestablishment of redox homeostasis in Brassica juncea.
As a vital osmoticum, proline has an important role in enhancing the tolerance of plants to environmental stress. It is unclear whether the application of exogenous proline can improve the tolerance of Brassica juncea to cadmium (Cd). This study investigated the effects of different concentrations of proline (20, 40, 60, 80, and 100 mg/L) under Cd stress at different times (0 d, 2 d, and 7 d) on the growth and physiology of B. juncea. Treatment with exogenous proline not only increased the content of proline in B. juncea but also alleviated Cd-induced seedling growth inhibition via the maintenance of higher photosynthetic pigment content and cell viability and a decrease in the content of Cd. Moreover, it increased the activities of antioxidant enzymes and the glutathione/glutathione disulfide ratio to reduce the accumulation of reactive oxygen species. Compared with other concentrations, 60 mg/L of exogenous proline was the most effective at mitigating Cd toxicity in B. juncea. Exogenous proline treatment enhanced the tolerance to Cd via a decrease in Cd accumulation and reestablishment of the redox homeostasis in B. juncea.


Induction of contraction in isolated rat aorta by cyclosporine.
Cyclosporine (CsA) is a new immunosuppressive agent that has adverse effects of nephrotoxicity and de novo appearance of hypertension. It has been hypothesized that the mechanism of the contrary effects is through an action of CsA on vascular smooth muscle. To test this hypothesis, thoracic aortas were isolated from Wistar Kyoto rats and ring segments prepared for measurement of tension. CsA (5 X 10(-6) M) induced a slow increase in tone of the isolated rings with a response at 3 hr of 0.70 +/- 0.17 N/m2 X 10(4). This contraction was significantly inhibited by the Ca2+ channel blocker verapamil (0.30 +/- 0.08 N/m2 X 10(4) after 3 hr, P less than 0.05) and by the noncompetitive alpha-antagonist phenoxybenzamine (0.06 +/- 0.07 N/m2 X 10(4) after 3 hr, P less than 0.05). The competitive alpha-antagonist phentolamine had mixed effects. CsA does not irreversibly alter vascular smooth muscle contractile ability since a 3 hr exposure to the agent had no effect on either the maximal contractile response or sensitivity to KCl. We conclude that CsA can directly induce contraction in vascular smooth muscle, perhaps by inducing a release of norepinephrine from adrenergic nerve terminals. The data are consistent with the hypothesis that CsA induces nephrotoxicity and de novo hypertension through a contractile effect on vascular smooth muscle.


Effect of Corilagin on the miR-21/smad7/ERK signaling pathway in a schistosomiasis-induced hepatic fibrosis mouse model.
This study sought to investigate the anti-fibrotic effect of Corilagin via interference with the miR-21/smad7/ERK signaling pathway in a schistosomiasis-induced hepatic fibrosis mouse model. Mice were infected with Schistosoma japonicum cercaria to establish the mouse model of schistosomiasis-induced hepatic fibrosis. At four weeks after infection, the groups were given different medications. The living conditions were observed. Real-time PCR was employed to detect the mRNA levels of miR-21, smad7 and connective tissue growth factor (CTGF), and western blotting was used to examine the protein levels of smad7, CTGF, smad1, p-smad1, smad2, p-smad2, ERK1/2, p-ERK1/2 and TGF-β receptor I. Immunohistochemistry was used to examine the expression of CTGF. Compared with the model group, increasing concentrations of Corilagin improved the quality of life, inhibited the mRNA expression of miR-21, promoted smad7 protein expression, and inhibited CTGF protein expression (p<0.05 or 0.01). Moreover, Corilagin significantly reduced the protein levels of p-smad1, p-smad2, p-ERK1/2, and TGF-β receptor I (p<0.05 or 0.01). CTGF staining in the cytoplasm was markedly decreased by Corilagin (p<0.05 or 0.01). In conclusion, Corilagin inhibited schistosomiasis-induced hepatic fibrosis via the miR21/smad7/ERK pathway in this animal model.


Kinetic characterization of CYP2E1 inhibition in vivo and in vitro by the chloroethylenes.
Trans- and cis-1,2-dichloroethylene (DCE) isomers inhibit their own metabolism in vivo by inactivation of the metabolizing enzyme, presumably the cytochrome P450 isoform, CYP2E1. In this study, we examined cytochrome P450 isoform-specific inhibition by three chloroethylenes, cis-DCE, trans-DCE, and trichloroethylene (TCE), and evaluated several kinetic mechanisms of enzyme inhibition with physiological models of inhibition. Trans-DCE was more potent than cis-DCE, and both were much more effective than TCE in inhibiting CYP2E1. The kinetics of in vitro loss of p-nitrophenol hydroxylase (pNP-OH) activity (a marker of CYP2E1) in microsomal incubations and of the in vivo gas uptake results were most consistent with a mechanism in which inhibition of the metabolizing enzyme (CYP2E1) was presumed to be related to interaction of a reactive DCE metabolite with remaining substrate-bound, active CYP2E1. The kinetics of inhibition by TCE, a weak inhibitor in vitro, were very different from that of the dichloroethylenes. With TCE, parent compound concentrations influenced enzyme loss. Trans-DCE was a more potent inhibitor of CYP2E1 than cis-DCE based on both in vivo and in vitro studies. Quantitative differences in the inhibitory properties of the 1,2-DCE isomers may be due to the different stability of epoxides formed from bioactivation by CYP2E1. Epoxide intermediates of DCE metabolism, reacting by water addition, would yield dialdehyde, a potent cross-linking reagent.


Synthesis, biological evaluation, and molecular docking studies of 1,3,4-oxadiazole derivatives possessing 1,4-benzodioxan moiety as potential anticancer agents.
In present study, a series of new 1,3,4-oxadiazole derivatives containing 1,4-benzodioxan moiety (6a-6s) as potential telomerase inhibitors were synthesized. The bioassay tests demonstrated that compounds 6k, 6l, 6m, 6n and 6s exhibited broad-spectrum antitumor activity with IC(50) concentration range from 7.21 μM to 25.87 μM against the four cancer cell lines, HEPG2, HELA, SW1116 and BGC823. Moreover, all the title compounds were assayed for telomerase inhibition using the TRAP-PCR-ELISA assay. The results showed compound 6k possessed the most potent telomerase activity (IC(50)=1.27 ± 0.05 μM). Docking simulation was performed to position compound 6k into the active site of telomerase (3DU6) to determine the probable binding model.


A long non-coding RNA LNBC3 facilitates non-small cell lung cancer progression by stabilizing BCL6.
The non-small cell lung cancer (NSCLC) is a common malignancy worldwide. Numerous reports have shown the critical role of long non-coding RNAs (lncRNAs) in NSCLC. However, the role of a novel lncRNA named LNBC3 is still unknown. By lncRNA profiling, novel lncRNAs related to NSCLC were identified. LNBC3 expression was quantified by qRT-PCR. Migration and viability assays were performed to evaluate the function of LNBC3 in vitro. In vivo xenograft model was conducted to determine the oncogenic functions of LNBC3. RNA immunoprecipitation (RIP) followed by mass spectrometry (MS) was utilized to identify BCL6 as LNBC3 binding target. LNBC3 is markedly overexpressed in tumor tissues and NSCLC cell lines. Higher LNBC3 levels correlated with advanced TNM stages, larger tumor size, and metastasis. LNBC3 promoted NSCLC migration and viability. The in vivo experiments demonstrated that xenograft tumor growth and proliferation were facilitated with increasing LNBC3 levels. The antisense oligonucleotides (ASOs) targeting LNBC3 substantially inhibited lung cancer progression. Mechanistic studies showed that LNBC3 could interact with BCL6 leading to BCL6 stabilization through reduced proteasomal degradation. Collectively, our data have identified a novel lncRNA LNBC3 in NSCLC progression. The LNBC3-BCL6 axis might be a potential target for pharmaceutical intervention.


Risk of acute kidney injury requiring hemodialysis after contrast-enhanced imaging after traumatic injury: A National Trauma Databank analysis.
Trauma patients undergo routine contrast administration for diagnostic and therapeutic purposes. The aim of this study is to investigate the incidence and predictors of contrast-induced nephropathy requiring acute hemodialysis in the trauma population. Adult patients (age ≥16) were identified from the National Trauma Databank (2017-2018) and were grouped based on contrast received. The defined groups included no contrast, computed tomography intravascular contrast only, and angiography contrast. Patient demographic and clinical variables collected included vital signs (systolic blood pressure, pulse rate) recorded upon arrival to the emergency room, injury severity score, shock index, Glasgow Coma Scale, and mechanism. Outcome measures included mortality, hospital discharge disposition, intensive care unit and hospital length of stay, and need for hemodialysis. We performed a Poisson regression to assess relative risk for undergoing hemodialysis during hospital admission. In total, 1,850,460 patients were included in the analysis (no contrast: 1,189,209; computed tomography intravascular contrast only: 621,846; angiography: 39,405); 3,135 patients required hemodialysis during the admission. Patients with reduced Glasgow Coma Scale, higher injury severity score, higher shock index, and preexisting diabetes mellitus and hypertension were more likely to require hemodialysis. Poisson regression revealed the relative risk of requiring hemodialysis as 1.49 with computed tomography intravascular contrast only, 4.33 with angiography only, and 5.35 with consecutive computed tomography intravascular and angiography. Intravascular contrast administration through computed tomography and or angiography is independently associated with increased risk of requiring hemodialysis after a traumatic injury. Trauma surgeons should consider the necessity of contrast for each clinical situation and understand the potential for contrast-induced nephropathy.


Nurses' competence in recognition and management of delirium in older patients: development and piloting of a self-assessment tool.
Delirium is a common condition in elderly inpatients. Health care professionals play a crucial role in recognizing delirium, initiating preventive measures and implementing a multicomponent treatment strategy. Yet, delirium often goes unrecognized in clinical routine. Nurses take an important role in preventing and managing delirium. This study assesses clinical reasoning of nurses using case vignettes to explore their competences in recognizing, preventing and managing delirium. The study was conducted as an online survey. The questionnaire was based on five case vignettes presenting cases of acutely ill older patients with different subtypes of delirium or diseases with overlapping symptoms. In a first step, case vignettes were developed and validated through a multidisciplinary expert panel. Scoring of response options were summed up to a Geriatric Delirium Competence Questionnaire (GDCQ) score including recognition and management tasks The questionnaire was made available online. Descriptive analyses and group comparisons explores differences between nurses from different settings. Factors explaining variance in participants' score were evaluated using correlations and linear regression models. The questionnaire demonstrated good content validity and high reliability (kappa = 0.79). The final sample consisted of 115 nurses. Five hundred seventy-five case vignettes with an accuracy of 0.71 for the correct recognition of delirium presence or absence were solved. Nurses recognized delirium best in cases describing hyperactive delirium (79%) while hypoactive delirium was recognized least (44%). Nurses from geriatric and internal medicine departments had significantly higher GDCQ-score than the other subgroups. Management tasks were correctly identified by most participants. Overall, nurses' competence regarding hypoactive delirium should be strengthened. The online questionnaire might facilitate targeting training opportunities to nurses' competence.


Unilateral elbow flexion fatigue modulates corticospinal responsiveness in non-fatigued contralateral biceps brachii.
Exercise-induced fatigue can change motor performance in non-exercised muscles. The objective was to investigate unilateral elbow flexion (EF) fatigue effects on the maximal voluntary force (MVC) and corticospinal excitability of contralateral non-exercised biceps brachii (BB). Transcranial magnetic, transmastoid electrical, and brachial plexus electrical stimulation were used to elicit motor evoked potentials (MEP), cervicomedullary motor evoked potentials (CMEP), and compound muscle action potentials in the contralateral non-exercised BB of 12 participants before and after (i) two bouts of 100-s unilateral EF (fatigue) or (ii) control. Three stimuli were evoked every 1.5 s during a series of 6-s isometric EF at 100%, 50%, and 5% of MVC. The non-exercised EF MVC force, electromyographic activity, and voluntary activation were not significantly different between fatigue and control. Non-exercised BB MEP and CMEP amplitudes during 100% MVCs demonstrated significantly higher (P = 0.03) and lower values (P = 0.01), respectively, after fatigue compared with control. There was no difference between the two conditions for MEP and CMEP amplitudes during 50% and 5% MVCs. Unilateral exercise-induced EF fatigue did not lead to cross-over central fatigue to the contralateral homologous muscle but enhanced the supraspinal responsiveness (MEP/CMEP) of the neural circuitries supplying central commands to non-exercised muscles at higher contraction intensity.


ADRB2 gene polymorphism and emphysema heterogeneity can modulate bronchodilator response in patients with emphysema.
Genetic variation in the β2-adrenergic receptor (ADRB2) gene has been thought to have an important role in the differential response to β2-agonist therapy for asthma. However, previous studies have shown little evidence for an association between these ADRB2 variants and the bronchial dilator response (BDR) in chronic obstructive pulmonary disease (COPD) patients. This discrepancy could be explained by differences in the distribution and heterogeneity of pulmonary emphysema in COPD patients, since emphysema distribution and heterogeneity are thought to have a role in pulmonary function in COPD patients. We hypothesized that differences in emphysema distribution and heterogeneity may have masked significant alterations of the bronchodilator response among ADRB2 genotypes in COPD patients in previous studies. The BDR (induced by 20 μg of procaterol) was measured in 211 patients who had a smoking history of more than 10 pack/years and had undergone chest high resolution computed tomography examination. A low attenuations area (<960 Hounsfield Units) was identified and the emphysema heterogeneity index (EHI%) was calculated with a range in value from -100% to 100%. ADRB2 Arg16Gly genotyping was performed using polymerase chain reaction-restriction fragment length polymorphism analysis. The BDR was augmented in patients with homogenous emphysema compared with those with upper-dominant emphysema. In patients carrying the AA genotype of ADRB2, the BDR was significantly increased in patients with upper-dominant emphysema, but not in patients with lower-dominant emphysema. Combination analysis of ADRB2 Arg16Gly polymorphism and EHI% may predict the effectiveness of β2-adrenergic receptor agonist treatment in patients with COPD and emphysema.


Advocacy in Pediatric Academia: Charting a Path Forward.
Pediatricians are effective advocates to improve the health and well-being of children, yet there are limited avenues by which to pursue academic promotion based on these activities. Drawing on an expanded definition of scholarship, pediatric advocates can use the portfolio format to highlight the quantity, quality, and impact of advocacy activities. True congruence with research and education will only be achieved through recognition and value by institutions and organizations.