Orientation sensitivity and texture segmentation in patterns with different line orientation.
Orientation sensitivity (OS) and the ability of human subjects to discriminate structured areas of different texture orientation (DOT) were investigated using line arrays of varying line length. In general, OS was mediated by shorter lines than was DOT; lines can be distinguished by their orientation before they give the impression of a texture border between adjacent regions with lines differing in orientation. This difference was found to hold over a range of retinal eccentricities from 5 degrees nasal to 30 degrees temporal. Decreasing visual acuity, associated with increasing distance from the fovea, cannot, however, account for the higher threshold of DOT, even taking into account that DOT requires a larger area for analysis than OS. When angle of orientation between adjacent texture areas was varied instead of line length, DOT thresholds at different retinal locations were reached at similar values. The difference between OS and DOT, found consistently at all retinal positions, suggests that they are mediated by distinct neural mechanisms.


Novel anti-aging herbal formulation Jing Si displays pleiotropic effects against aging associated disorders.
Common characteristics of aging include reduced somatic stem cell number, susceptibility to cardiac injuries, metabolic imbalances and increased risk for oncogenesis. In this study, Pleiotropic anti-aging effects of a decoction Jing Si herbal drink (JS) containing eight Traditional Chinese Medicine based herbs, with known effects against aging related disorders was evaluated. Adipose derived mesenchymal stem cells (ADMSCs) from 16 week old adult and 24 month old aging WKY rats were evaluated for the age-related changes in stem cell homeostasis. Effects of JS on self-renewal, klotho and Telomerase Reverse Transcriptase expression DNA damage response were determined by immunofluorescence staining. The effects were confirmed in senescence induced human ADMSCs and in addition, the potential of JS to maintain telomere length was evaluated by qPCR analysis in ADMSCs challenged for long term with doxorubicin. Further, the effects of JS on doxorubicin-induced hypertrophic effect and DNA damage in H9c2 cardiac cells; MPP+-induced damages in SH-SY5Y neuron cells were investigated. In addition, effects of JS in maintaining metabolic regulation, in terms of blood glucose regulation in type-II diabetes mice model, and their potential to suppress malignancy in different cancer cells were ascertained. The results show that JS maintains stem cell homeostasis and provides cytoprotection. In addition JS regulates blood glucose metabolism, enhances autophagic clearances in neurons and suppresses cancer growth and migration. The results show that JS acts on multiple targets and provides a cumulative protective effect against various age-associated disorders and therefore it is a candidate pleiotropic agent for healthy aging.


The toroidal field surfaces in the standard poloidal-toroidal representation of magnetic field.
The representation of magnetic field as a sum of a toroidal field and a poloidal field has not rarely been used in astrophysics, particularly in relation to stellar and planetary magnetism. In this representation, each toroidal field line lies entirely in a surface, which is named a toroidal field surface. The poloidal field is represented by the curl of another toroidal field and it threads a stack of toroidal field surfaces. If the toroidal field surfaces are either spheres or planes, the poloidal-toroidal (PT) representation is known to have a special property that the curl of a poloidal field is again a toroidal field . We name a PT representation with this property a standard PT representation while one without the property is called a generalized PT representation. In this paper, we have addressed the question whether there are other toroidal field surfaces allowing a standard PT representation than spheres and planes. We have proved that in a three dimensional Euclidean space, there can be no standard toroidal field surfaces other than spheres and planes, which render the curl of a poloidal field to be a toroidal field.


Time-dependent recovery of in vivo binding sites after drug dosing: a method for radiotracer evaluation.
The recovery of in vivo binding sites for (+/-)-alpha-[11C] methoxytetrabenazine, a radioligand for the monoamine vesicular transporter (VMAT2), was determined in mouse brain at various times following a pharmacological dose of tetrabenazine. Concentrations of in vivo radioligand binding sites progressively increased and had reached control values by 8.5 h, and this recovery was consistent with the pharmacokinetics of the competing drug tetrabenazine and its active metabolite, dihydrotetrabenazine. This study demonstrates a simple experimental protocol of using a single dose of a reversible competing drug and time-dependent measurements of in vivo binding of a radioligand. This protocol is suitable for testing the sensitivity of an in vivo radiotracer for measurement of varying concentrations of in vivo binding sites.


Differential toxic effects of methamphetamine (METH) and methylenedioxymethamphetamine (MDMA) in multidrug-resistant (mdr1a) knockout mice.
The toxic effects of methamphetamine (METH) (2.5, 5.0 and 10.0 mg/kg) and methylenedioxymethamphetamine (MDMA) (5.0, 10.0 and 20.0 mg/kg) on dopaminergic systems were assessed in the striatum and of the nucleus accumbens in mdr1a wild-type and knockout mice. METH caused significant dose-dependent decreases of dopamine (DA) and DA transporters (DAT) in the striatum and the nucleus accumbens (NAc) of both wild-type and knockout mice. The lowest doses of METH (2.5 mg/kg) caused only small changes in the wild-type, but marked. decreases in the mdr1a knockout mice. The two higher doses (5 mg/kg and 10 mg/kg) caused similar changes in both strains of mice. In contrast to METH, MDMA caused greater percentage decreases in DAT in the wild-type mice. For example, the lowest dose (5 mg/kg) caused significant decreases in DAT in the NAc of wild-type but not of mdr1a knockout mice. The highest dose (20 mg/kg) caused similar changes in both the strains. These results suggest that METH and MDMA interact differentially with P-glycoproteins. These observations document, for the first time, a role for these proteins in the entry of METH and MDMA into the brain via the blood-brain barrier, with P-glycoprotein possibly facilitating the entry of MDMA but interfering with that of METH into the brain.


Marijuana But Not Alcohol Use During Adolescence Mediates the Association Between Transmissible Risk for Substance Use Disorder and Number of Lifetime Violent Offenses.
AIM: This study determined the extent to which alcohol and marijuana use during adolescence mediates the relation between transmissible risk for substance use disorder (SUD) and lifetime number of different types of violent offenses. METHODS: The transmissible liability index was administered to 359 10-12 year old youths who were tracked to 22 years of age. Past year frequency of alcohol and marijuana consumption was longitudinally tracked to age 22 at which time lifetime violent offenses was recorded. RESULTS: Rate of increase in marijuana use mediated the association between transmissible risk and lifetime number of different types of violent offenses. No association was found between past year frequency of alcohol use and violent offenses. CONCLUSIONS: Prevention directed at lowering the psychological characteristics associated with transmissible risk for SUD may also reduce violent offending.


Modulation of inhibition in a model of olfactory bulb reduces overlap in the neural representation of olfactory stimuli.
In a neural model of olfactory bulb processing, we demonstrate the putative role of the modulation of two types of inhibition, inspired by electrophysiological data on the effect of acetylcholine and noradrenaline on olfactory bulb synaptic transmission. Feedback regulation of modulation based on bulbar activity serves to 'normalize' the activity of output neurons in response to different levels of input activities. This mechanism also decreases the overlap between pairs of output patterns (Mitral cell activities), enhancing the discrimination between overlapping olfactory input patterns. The effect of the modulation at the two levels of interneurons is complementary: while an increase in periglomerular inhibition decreases the number of responding output neurons, a decrease in granule cell inhibition increases the firing frequencies of these neurons.


Anal human papillomavirus infection and its relationship with abnormal anal cytology among MSM with or without HIV infection in Japan.
Anal high-risk human papillomavirus (hr-HPV) infection is widely considered a cause of anal cancer. However, epidemiological data are quite limited in Japan. This study investigated anal HPV infections and cytological abnormalities among MSM with or without HIV infection. Anal swabs were obtained, and cytological results were examined. Hybrid capture-based methodology was used for hr-HPV genotyping. The exclusion criterion was a history of vaccination against HPV. 644 subjects participated, and the overall prevalence of hr-HPV was 59.7% (95% CI 54.7-62.3), HIV-infected had higher prevalence than HIV-uninfected (68.9% vs 40.6%) p < .001. Among hr-HPV-infected participants, 82.8% (312/377) were infected with at least one of 9 valent vaccine-covered hr-HPV genotypes. From regression analysis, detection of abnormal cytology correlated positively with HIV infection (OR 2.17 [95% CI 1.51-3.13]), number of hr-HPV genotypes infected (OR 1.83 [1.59-2.10]), history of STI (OR 1.58 [1.14-2.22]) and No. of lifetime sexual partners (OR 1.56 [1.10-2.21]), albeit multivariate analysis identified the number of detected hr-HPV genotypes (adjusted OR 1.78 [1.54-2.06]) as the independent risk factor for abnormal cytology. High rates of anal hr-HPV infection, especially 9-valent HPV vaccine-preventable hr-HPV were detected among our MSM participants in Japan. HPV vaccination should also be encouraged for MSM in Japan.


Endocrine disrupting compounds modulates adiponectin secretion, expression of its receptors and action on steroidogenesis in ovarian follicle.
We determined the effect of dioxin-like polychlorinated naphtalenes (PCN) (Halowax 1051) (100pg/ml), benzo(a)pyrene [B(a)P] (2.5ng/ml), hexachlorobenzene (HCBz) (0.2ng/ml) and non-dioxin like polybrominated diphenyl ether (BDE-47) (25ng/ml) and bisphenol A (BPA) (20ng/ml) on ovarian adiponectin secretion (ELISA) and its receptors expression (Western blot). Ovarian cells co-culture was used to examine action of endocrine disruptors (EDCs) on adiponectin (10μg/ml) stimulated steroidogenesis. B(a)P, HCBz, testosterone (T) decreased adiponectin secretion and receptors expression, BPA, BDE-47, estradiol (E2) had the opposite effect, while PCN had inhibitory effect only on adiponectin secretion. In adiponectin stimulated cells dioxin-like compounds decreased E2 and except of PCN had no effect on T, while non-dioxin like increased E2 and decreased T secretion. Results indicated to modulatory role of EDCs on adiponectin and its receptor and its action on ovarian steroidogenesis, suggest that dioxin- like compounds may contribute to the ovarian dysfunction in obesity-related disorders.


Assessment of myocardium at risk with computerized vectorcardiography and technetium-99m-sestamibi-single photon emission computed tomography during coronary angioplasty.
To compare the myocardium at risk (MAR) as estimated by computerized vectorcardiography (cVCG) with MAR determined by Tc-99m-sestamibi-SPECT using coronary angioplasty as the model for transient transmural ischemia in humans. In 37 patients with stable angina pectoris, cVCG was recorded continuously during coronary angioplasty. The scintigraphic defect was quantified using an automated software program (CEqual). The ST vector magnitude (ST-VM) and the ST change vector magnitude (STC-VM) correlated well with MAR estimated by scintigraphy, ST-VM (r = 0.71, p < 0.001) and STC-VM (r = 0.84, p < 0.001). All patients with STC-VM <50 microV during occlusion had defects of less than 10% of the left ventricle. 1) ST-VM and STC-VM give a reasonable useful estimate of MAR size during transient coronary occlusion. 2) STC-VM <50 microV is a reliable limit to identify patients with MAR size less than 10%. 3) ST-VM does not add information to STC-VM with respect to detection of ischemia. 4) The existence of collateral vessels has great impact on both ST-vector changes and scintigraphic imaging of myocardial ischemia.


Management of Obesity and Its Complications in Children and Adolescents.
Pediatric overweight/obesity has assumed epidemic proportions in India. It is associated with several significant complications and tracks into adulthood. The mainstay of management is a holistic lifestyle modification that must be adopted by the family as a whole. It involves dietary changes, regular physical activity, and behavioral changes that favor a healthy way of life. Regular follow-up, and attention to keeping up the motivation of the child and family achieves good results. In the present paper, a stepwise approach to prevention and management of childhood obesity is presented along with the recommendations for screening and management of associated complications and the role of pharmacotherapy and bariatric surgery.


Work of breathing in children with diffuse parenchymal lung disease.
Respiratory mechanics have been poorly studied in children with chronic diffuse parenchymal lung disease (DPLD). The aim of the study was to assess the usefulness of respiratory mechanics to monitor lung function alteration in children with DPLD. Respiratory mechanics, total (WOBt), elastic (WOBe) and resistive (WOBr) work of breathing, gas exchange, lung function and respiratory muscle strength were measured in 10 children, aged 1.8-18.4 years old, who were followed in our national reference centre. Mean tidal volume (Vt) was normal (11±4mL/kg) but respiratory rate (fr, 32±19breaths/min), fr/Vt (118±75breaths/min/L) and total lung resistance (10.2±4.8cmH2OL(-1)s) were increased. Mean WOBt was increased mainly due to WOBe. Dynamic lung compliance (Cldyn) was severely reduced (26±24mL/cmH2O). Cldyn and the oesophageal pressure-time product strongly correlated with vital capacity and functional residual capacity. Respiratory muscle strength was within the normal range. In conclusion, lung mechanics may be considered as useful complementary or alternative markers of functional abnormalities in children with DPLD.


An approach for water-inrush risk assessment of deep coal seam mining: a case study in Xinlongzhuang coal mine.
Most coal mines in China are opting for deep mining due to the rapid reduction of shallow coal reserves, which increases the risk of water-inrush accidents. Given the limitation of water-inrush coefficient method in evaluating the risk of water inrush from the coal seam floor, we analyzed the permeability resistance of the floor under different lithology combinations, and structural conditions of the lower group coal in Yanzhou mining area, based on the in situ pressure permeability test data. Our comprehensive analysis of the influencing factors of water inrush from the coal seam floor reveals key indices for evaluating the water inrush from the coal seam floor and also recommend values for average water-resistance strength of the different lithology, and structure of the lower coal seam floor of Xinglongzhuang coal mine. Besides, we establish a model based on the water-resistance conditions, and two adjacent lower coal working faces minefields of Xinglongzhuang coal mine in Yanzhou are used for the evaluation. Comparative analysis of water-inrush coefficient method and impermeability resistance condition to evaluate the applicability of safety conditions of coal mining under pressure are also performed. Our results show that the impermeability strength is a better measurement for the water-resistance capacity of the floor. These findings may guide the prevention and control of water disasters in coal mining under pressure in the lower formation of the minefield.


Hypotensive activity of TCV-116, a newly developed angiotensin II receptor antagonist, in spontaneously hypertensive rats.
TCV-116, a recently developed angiotensin II (Ang II) receptor antagonist, was administered orally (1 mg/kg per day) to 10-week-old spontaneously hypertensive rats (SHR) for 2 weeks. Blood pressure and plasma components of the renin-angiotensin-aldosterone system were determined in these rats. TCV-116 produced a marked reduction in blood pressure without altering heart rate. Whereas plasma renin concentration (PRC), angiotensin I (Ang I) and angiotensin II (Ang II) all were significantly increased, plasma aldosterone was decreased by approximately 70% compared with control animals. These results not only indicate therapeutic efficacy of this agent in the chronic treatment of human hypertension, but support also the concept that the renin-angiotensin system plays an important role in the control of blood pressure in this animal model of human essential hypertension.


Culture media for mouse oocyte maturation affect subsequent embryonic development.
These experiments were done to determine whether the culture medium used for the spontaneous maturation of mouse oocytes can affect the subsequent capacity of the ova to become fertilized and complete preimplantation development in vitro and development to live young. Oocytes obtained from antral follicles of gonadotropin-primed immature mice underwent spontaneous maturation in control medium, i.e. Eagle's Minimum Essential Medium (MEM) supplemented with 5% fetal bovine serum, or in one of eight different media which were also supplemented with serum. All of the ova were fertilized in Whitten's medium and were assessed for cleavage to the 2-cell stage and for further preimplantation development to blastocysts during culture in Whitten's medium. Three of the eight media used for oocyte maturation improved the capacity of the ova to develop to the blastocyst stage when compared with the control: Waymouth MB 752/1, MEM with non-essential amino acids, and MEM Alpha; Waymouth medium promoted the highest frequency of development of ova to the blastocyst stage. Moreover, the blastocysts derived from oocytes that matured in Waymouth medium contained more cells than blastocysts derived from oocytes that matured in control medium. Although BGJb medium promoted the cleavage of eggs to the 2-cell stage when present during oocyte maturation, it had a detrimental effect on their subsequent preimplantation developmental capacity. Following transfer to foster mothers, more 2-cell stage embryos developed to live young after oocyte maturation in Waymouth medium (21%) than in control medium (13%).(ABSTRACT TRUNCATED AT 250 WORDS)


Vermiwash: An agent of disease and pest control in soil, a review.
Vermiwash is a liquid extract produced from vermicompost in a medium where earthworms are richly populated. It comprises a massive decomposer bacteria count, mucus, vitamins, different bioavailable minerals, hormones, enzymes, different antimicrobial peptides, etc. This paper aimed to assess how these natural products in vermiwash suppressed the pathogen and pests. Thus, we have reviewed the importance of vermiwash/vermicompost in disease control, the mechanism of disease suppression, the components of vermiwash applied in disease suppression, and pest control to use the scientific facts in agriculture to enhance the productivity of the crops. The bioactive macromolecules from the skin secretion of earthworm, coelomic fluid, and mucus directly able to defend pathogenic soil microbes against the worm and thereby freed the environment from the disease. Earthworms establish symbiotic relations with microbes, produce an essential product that supports the growth of plants, and suppress plant's root disease. It is recomended that earthworm should be inoculated in an agricultural field, or prepare and apply its vermiwash/vermicompost as a spray or as additive bio-fertilizer in the soil to enhance the productivities of the crops.


A tool for developing gender research in medicine: examples from the medical literature on work life.
Interest is growing both in implementing a gender perspective in medical research and in developing gender research. However, few models exist that can help researchers who want to develop gender research. The objectives of this article were to analyze gender research compared with sex/gender blind research as well as with research on sex/gender differences in work-life research, and to propose a tool that can be used by researchers who want to develop gender research. Using the PubMed database, the search period for the main analyses covered January 1, 2000, to November 1, 2006. In the first of 2 searches, the search criteria were English language and the term unemployment. In the second search, the criteria used were English language and 3 combinations of search terms: (1) underemploy or employ and (fixed-term or types or temporary or atypical or precarious or casual); (2) labor market and (attachment or core periphery or trajectory); and (3) job and (flexibility or casual). The number of articles about women and gender in unemployment research that are available in PubMed steadily increased during the 1990s. The proposed model could be regarded as a tool that by necessity is simplified. The tool should not be interpreted as if all research fulfills all the characteristics in the model; rather, the tool illustrates the potentials with gender research. Whereas gender research questions the dominating epistemology of medicine (eg, through challenging biological determinism), the other 2 research traditions are often performed within the dominating medical paradigm. Gender is an analytic category, and structural analyses of gender relations are central in medical gender research, whereas sex/gender is often analyzed as a variable on the individual level in other research. Masculinity research constitutes a dynamic part of gender research. However, in other research, men as well as women are often analyzed as one of several variables. Through questioning the existing field of knowledge, gender research, with its base in power analyses and theoretical development, can provide new and different knowledge about men and women. In gender research, there has been an increasing awareness of the need for vigilance to avoid exaggerating differences (both biological and sociocultural) between men and women. Thus, the risk of essentialism (ie, the tendency to regard differences between men and women as constant, pervasive, and unchangeable) is lower than in other research. A model has been suggested that may be used to implement gender research. This tool needs continuous development through active dialogue between gender researchers.


Perceptions of Justice By Algorithms.
Artificial Intelligence and algorithms are increasingly able to replace human workers in cognitively sophisticated tasks, including ones related to justice. Many governments and international organizations are discussing policies related to the application of algorithmic judges in courts. In this paper, we investigate the public perceptions of algorithmic judges. Across two experiments (N = 1,822), and an internal meta-analysis (N = 3,039), our results show that even though court users acknowledge several advantages of algorithms (i.e., cost and speed), they trust human judges more and have greater intentions to go to the court when a human (vs. an algorithmic) judge adjudicates. Additionally, we demonstrate that the extent that individuals trust algorithmic and human judges depends on the nature of the case: trust for algorithmic judges is especially low when legal cases involve emotional complexities (vs. technically complex or uncomplicated cases). The online version contains supplementary material available at 10.1007/s10506-022-09312-z.


Molecular characterization of frog vocal neurons using constellation pharmacology.
Identification and characterization of neuronal cell classes in motor circuits are essential for understanding the neural basis of behavior. It is a challenging task, especially in a non-genetic-model organism, to identify cell-specific expression of functional macromolecules. Here, we performed constellation pharmacology, calcium imaging of dissociated neurons to pharmacologically identify functional receptors expressed by vocal neurons in adult male and female African clawed frogs, Xenopus laevis. Previously we identified a population of vocal neurons called fast trill neurons (FTNs) in the amphibian parabrachial nucleus (PB) that express N-methyl-d-aspartate (NMDA) receptors and GABA and/or glycine receptors. Using constellation pharmacology, we identified four cell classes of putative fast trill neurons (pFTNs, responsive to both NMDA and GABA/glycine applications). We discovered that some pFTNs responded to the application of substance P (SP), acetylcholine (ACh), or both. Electrophysiological recordings obtained from FTNs using an ex vivo preparation verified that SP and/or ACh depolarize FTNs. Bilateral injection of ACh, SP, or their antagonists into PBs showed that ACh receptors are not sufficient but necessary for vocal production, and SP receptors play a role in shaping the morphology of vocalizations. Additionally, we discovered that the PB of adult female X. laevis also contains all the subclasses of neurons at a similar frequency as in males, despite their sexually distinct vocalizations. These results reveal novel neuromodulators that regulate X. laevis vocal production and demonstrate the power of constellation pharmacology in identifying the neuronal subtypes marked by functional expression of cell-specific receptors in non-genetic-model organisms.NEW & NOTEWORTHY Molecular profiles of neurons are critical for understanding the neuronal functions, but their identification is challenging especially in non-genetic-model organisms. Here, we characterized the functional expression of membrane macromolecules in vocal neurons of African clawed frogs, Xenopus laevis, using a technique called constellation pharmacology. We discovered that receptors for acetylcholine and/or substance P are expressed by some classes of vocal neurons, and their activation plays a role in the production of normal vocalizations.


Expression, localization and alternative splicing pattern of fibronectin messenger RNA in fibrotic human liver and hepatocellular carcinoma.
Fibronectin is a multifunctional glycoprotein and plays important roles in cell-to-cell or cell-to-matrix interaction. The molecular and functional diversity of fibronectin arises from alternative splicing of pre-mRNA at three variable regions, termed ED-A, ED-B and IIICS. Cellular fibronectin with ED-A and ED-B regions has different biological activities from plasma fibronectin lacking these regions. This study was aimed at investigating the type-specific expression of fibronectin in human liver diseases. Immunohistochemistry with anti-total and anti-cellular fibronectin monoclonal antibodies, in situ hybridization with cDNA probes detecting common and ED-A regions and RT-PCR to amplify each variable region were performed in 35 specimens, including 4 control, 16 chronic hepatitis, 7 liver cirrhosis and 8 hepatocelular carcinoma. In control liver, there were slight deposits of cellular fibronectin [ED-A(+)fibronectin] in portal areas. In chronic hepatitis, it was strongly deposited at the margin of the fibrously enlarged portal areas where new collagen fibers were formed. Cellular fibronectin was evenly and abundantly accumulated in fibrotic septa in liver cirrhosis, and in fibrotic septa and capsules of tumor nodules in hepatocellular carcinoma. In control liver, cellular fibronectin mRNA was localized in a few hepatocytes and non-parenchymal cells around central veins, and was increased in the same cell populations near fibrously enlarged portal areas as hepatic fibrosis progressed. In hepatocellular carcinoma, it was expressed in most hepatoma cells. Fibronectin mRNA with three variable regions was detectable by RT-PCR in control liver as well as in each disease group. The expression of cellular fibronectin was increased in fibrotic human liver and hepatocellular carcinoma. In human liver, both non-parenchymal cells and hepatocytes participated together in cellular fibronectin production. In hepatocellular carcinoma, hepatoma cells were the main producer. Our results indicate that, in human liver, cellular fibronectin may participate in the hepatic fibrogenesis and in the malignant phenotypes of hepatocellular carcinoma.


A novel coupled-cluster singles and doubles implementation that combines the exploitation of point-group symmetry and Cholesky decomposition of the two-electron integrals.
A novel implementation of the coupled-cluster singles and doubles (CCSD) approach is presented that is specifically tailored for the treatment of large symmetric systems. It fully exploits Abelian point-group symmetry and the use of the Cholesky decomposition of the two-electron repulsion integrals. In accordance with modern CCSD algorithms, we propose two alternative strategies for the computation of the so-called particle-particle ladder term. The code is driven toward the optimal choice depending on the available hardware resources. As a large-scale application, we computed the frozen-core correlation energy of buckminsterfullerene (C60) with a polarized valence triple-zeta basis set (240 correlated electrons in 1740 orbitals).


[Effect of lymphokine activated killer from umbilical blood on human ovarian cancer in nude mouse models].
To explore the possibility of using lymphokine activated killer (LAK) from cord blood as an adoptive immunotherapy for ovarian cancer. The nude mouse models with human ovarian cancer were treated with the LAK from cord blood and compared with those treated with the LAK from the pheripheral blood. The LAK from the cord blood inhibited the growth of human ovarian cancer. The average size of the tumor was 6.0 mm3 23 days after the cord blood LAK treatment, with an average weight of (0.674 +/- 0.45 g). Cord blood can be a source of adoptive cellular immunotherapy for the treatment of ovarian cancer.


Application of the Bethesda system of reporting for cervical cytology to evaluate human papilloma virus induced changes in oral leukoplakia, oral squamous cell carcinoma, and oropharyngeal squamous cell carcinoma: A cytomorphological and genetic study.
Human papilloma virus (HPV) has a well-established carcinogenic role in certain head and neck cancers. These HPV associated cancers possess unique clinicopathological behavior and exhibits better prognosis than their negative counterparts. Detection through polymerase chain reaction (PCR) has been considered as the "gold standard" but imposes burden in low resource settings. Therefore, in the present study, we assessed the validity of cytomorphological features for the detection of HPV in oral leukoplakia (OL), oral squamous cell carcinoma (OSCC), and oropharyngeal squamous cell carcinoma (OPSCC). This study included 63 subjects comprising of 25 OL, 26 OSCC, and 12 OPSCC cases. Exfoliated cells were collected and processed for PCR followed by Papanicolaou staining and subsequent grading. Additionally the non-classical signs were evaluated and statistical analysis included Chi-square and Spearman's test. 23/63 (36.5%) cases showed PCR positivity for HPV16. Most of the cytomorphological features showed significant correlation for the presence of HPV. A greater sensitivity and specificity was observed in the Bethesda system for reporting cervical cytology (TBS) than the Papanicolaou grading system. We conclude that the non-classic cytological features could be employed in the detection of HPV in low resource settings with improved sensitivity. Liquid based cytology graded using TBS could be suitable for oral cytology in the detection of early atypical changes.


User experiences of older adults navigating an online database of community-based physical activity programs.
This study aimed to (1) explore older adult user experiences navigating an online health database of local physical activity programs; (2) compare navigational feedback with age-friendly website design guidelines; (3) assess online database completeness. Focus groups, including guided tasks and a semi-structured interview script, gathered navigational user experiences of fifteen older adults. A review of the literature sought age-friendly best practice website design guidelines and a website search for local physical activity programs was completed. The design of the online database website was challenging for older adult participants to navigate and was not 'intuitive'. Based on focus group feedback, there were multiple discrepancies between the evaluated online database and the established guidelines for designing age-friendly websites. A total of 187 physical activity programs were missing from the database. Findings provide novel insight into user experiences of older adults navigating online health and physical activity program sites. Redesigning the following age-friendly website recommendations would empower older adults in the use of online databases and promote awareness of local physical activity programs. Health care providers need reliable and age-friendly online resources to link their patients with local physical activity programs to promote healthy aging.


Protocol of a 12-month multifactorial eHealth programme targeting balance, dual-tasking and mood to prevent falls in older people: the StandingTall+ randomised controlled trial.
Falls have a multifactorial aetiology, which may limit the effectiveness of the common approach of exercise as the sole intervention strategy. Multifactorial interventions could be more effective in people at high risk of falling; however, the focus of such interventions has traditionally been quite narrow. This paper describes the design of a randomised controlled trial that will evaluate the effectiveness of an eHealth programme, which addresses cumulative effects of key fall-risk factors across the triad of physical, affective and cognitive functions on falls in older people. 518 older people aged 65 years and over with high fall risk, defined as having a history of falls in the past 6 months, self-reported fear of falling or being aged 80 years or over, will be recruited via local advertisements, newsletters and presentations, and randomised to an intervention or health education control group. The intervention comprises balance exercise, cognitive-motor exercise and cognitive-behavioural therapy, with their dosage based on participant's baseline balance, executive function and mood. The primary outcome is the rate of falls in the 12 months after randomisation. Secondary outcomes at 6 and 12 months comprise programme adherence, healthcare use, physical activity, balance and mobility, cognitive function, psychological well-being, quality of life, health literacy and user experience and attitudes towards the programme. Data will be analysed following intention to treat to gauge real-world effectiveness. We will further determine complier averaged causal effects to correct for varying adherence and conduct economic analyses to gain insight into cost-effectiveness and cost-utility. Ethical approval was obtained from the University of New South Wales (UNSW) Human Research Ethics Committee in December 2017. Outcomes will be disseminated via peer-reviewed articles, conference presentations, community events and media releases. ACTRN12619000540112.


Selective Production of Secondary Amine by the Photocatalytic Cascade Reaction Between Nitrobenzene and Benzyl Alcohol over Nanostructured Bi2 MoO6 and Pd Nanoparticles Decorated with Bi2 MoO6.
The synthesis of secondary amine by the photoalkylation of nitrobenzene with benzyl alcohol using a simple light source and sunlight is a challenging task. Herein, a one-pot cascade protocol is employed to synthesize secondary amine by the reaction between nitrobenzene and benzyl alcohol. The one-pot cascade protocol involves four reactions: (a) photocatalytic reduction of nitrobenzene to aniline, (b) photocatalytic oxidation of benzyl alcohol to benzaldehyde, (c) reaction between aniline and benzaldehyde to form imine, and (d) photocatalytic reduction of imine to a secondary amine. The cascade protocol to synthesize secondary amine is accomplished using Bi2 MoO6 and Pd nanoparticles decorated Bi2 MoO6 catalysts. The surface characteristics, oxidation states, and elemental compositions of the materials are characterized by several physicochemical characterization techniques. Optoelectronic and photoelectrochemical measurements are carried out to determine the bandgap, band edge potentials, photocurrents, charge carrier's separation, etc. An excellent yield of secondary amine is achieved with simple household white LED bulbs. The catalyst also exhibits similar or even better activity in sunlight. The structure-activity relationship is established using catalytic activity data, control reactions, physicochemical, optoelectronic characteristics, and scavenging studies. Bi2 MoO6 and Pd nanoparticles decorated Bi2 MoO6 exhibit excellent photostability and recyclability. The simple catalyst design with a sustainable and economical light source for the synthesis of useful secondary amine from the nitrobenzene and benzyl alcohol would attract the researchers to develop similar catalytic protocols for other industrially important chemicals.


Non-alcoholic fatty liver disease in children.
Non-alcoholic fatty liver disease is increasingly prevalent in children, together with obesity. Transaminases, tests for insulin resistance, ultrasonography and MRI are variably used as surrogates markers of steatosis. Other liver diseases, such as Wilson disease, should be excluded. A liver biopsy is performed in selected cases: young children, familial history of severe disease, inconclusive tests for other pathologies, suspected advanced fibrosis, hypertransaminasemia despite weight loss and in clinical trials. Weight reduction, and changes in lifestyle, are the front-line treatment. Drug therapy is under evaluation.


Patients with post-transplant biliary strictures have significantly higher rates of liver transplant failure and rejection: A nationwide inpatient analysis.
Biliary strictures are a common complication of liver transplantation. We assess the impact of post-transplant biliary strictures and describe the outcomes of endoscopic retrograde cholangiopancreatography (ERCP), interventional radiology (IR), and surgical therapies. Using the Nationwide Readmissions Database (NRD), hospitalized liver transplant recipients were identified using the International Classification of Diseases 10th Revision codes. Patients with post-transplant biliary strictures were identified, and outcomes (inpatient mortality, 30-day readmission, transplant rejection/infection/failure, and disposition) were compared with transplant recipients without strictures. Among transplant patients with biliary strictures who underwent therapeutic intervention, corresponding outcomes were compared between IR, surgical interventions, and ERCP. Of the 8300 liver transplant recipients meeting selection criteria, 554 patients (age 48.9 ± 18.2 years, mean ± SD; 39.5% women) had biliary strictures. Compared with patients without strictures, the adjusted odds ratio (OR) for various outcomes in patients with biliary strictures were as follows: 1.46 (1.20, 1.77; P < 0.001) for 30-day non-elective readmission, 2.71 (2.04, 3.59; P < 0.001) allograft rejection, 2.32 (1.61, 3.37; P < 0.001) liver transplant failure, 3.05 (1.39, 6.73; P < 0.01) infection, and 1.41 (1.08, 1.82; P = 0.01) disposition to skilled nursing or intermediate care facility. Therapeutic interventions during index hospitalization were performed in 350 patients: ERCP 46.6% (n = 163), surgery 41% (n = 144), and IR 12.3% (n = 43) patients. Compared with ERCP, the adjusted odds for various outcomes were disposition to skilled nursing or intermediate care facility 2.72 (1.08, 6.87; P = 0.03) and 2.09 (1.05, 4.15; P = 0.036), prolongation of hospitalization 14.4 (3.7, 25.1; P = 0.008) and 15.0 (7.4, 22.7; P < 0.001), and failure of liver allograft 8.47 (1.47, 48.6; P = 0.017) and 12.23 (2.74, 54.4; P = 0.001) for IR and surgical interventions, respectively. Post-liver transplant biliary strictures are associated with increased rates of allograft rejection, allograft failure/infections, and readmissions. Compared with ERCP, management of these patients with IR or surgical interventions is associated with significantly higher rates of allograft failure and hospital stay.


Comparison of A-Scan ultrasonography and the Lenstar optical biometer in Guinea pig eyes.
To compare the biometric parameters provided by A-scan ultrasonography and the Lenstar optical biometer in guinea pig eyes, including anterior segment depth (ASD), lens thickness (LT), vitreous chamber depth (VCD), and axial length (AL), and differences of them between treated form deprivation (FD) eyes and untreated fellow eyes after 4 weeks of FD. Three-week-old guinea pigs (N = 41) were subjected to biometric measurements before monocular FD (baseline) and after a 4-week FD. Statistical analyses including within-subject standard deviation (SDwithin), coefficient of variation (CV), and intraclass correlation coefficient (ICC), used to evaluate repeatability for both the A-scan ultrasonography and the Lenstar individually, and correlation and Bland-Altman analyses were used to assess agreement between the two methods. The absolute values of ASD, LT, VCD and AL as measured by the two devices were compared, and the differences of them between treated (T) and untreated fellow (F) eyes (ΔASD, ΔLT, ΔVCD and ΔAL) (Δ = T-F) were compared between the two devices after 4 weeks of FD. Measurements by the Lenstar (ICC: 0.923-0.994) were more repeatable than A-scan ultrasonography (ICC: 0.825-0.870). There was a high correlation for AL (r = 0.851, P < 0.001), a moderate correlation for VCD (r = 0.571, P < 0.001) and LT (r = 0.423, P < 0.001), and a low correlation for ASD (r = 0.230, P < 0.01) between the two devices. The values for ASD, VCD and AL measured by A-scan ultrasonography were larger than those measured by the Lenstar (all, P < 0.001), while LT provided by A-scan ultrasonography was much smaller than that of the Lenstar (P < 0.001). Bland-Altman plots showed poor agreement of absolute values of the four parameters between the two devices. Moreover, there was a high correlation between both methods for ΔAL (r = 0.704, P < 0.001), a moderate correlation for ΔVCD (r = 0.534, P < 0.001) and ΔASD (r = 0.574, P < 0.001), and no correlation for ΔLT (r = 0.303, P = 0.054). The ΔASD, ΔLT, and ΔAL measurements obtained by A-scan ultrasonography were greater than those obtained by the Lenstar (all, P < 0.001), while ΔVCD was mildly smaller using A-scan ultrasonography (P < 0.05). Bland-Altman plots illustrated there is good agreement of ΔAL, ΔVCD, ΔASD, and ΔLT between the two devices. The Lenstar exhibited better repeatability and provided smaller measurements for AL, VCD and ASD than A-scan ultrasonography. Furthermore, a high correlation and a good agreement for the ΔAL was observed between the two devices after a period of FD. In summary, the two devices cannot replace each other directly to obtain absolute values of ASD, LT, VCD and AL, but the Lenstar still can serve as an option in measuring ΔAL between eyes in guinea pig myopia model.


Iron oxide/hydroxide-nitrogen doped graphene-like visible-light active photocatalytic layers for antibiotics removal from wastewater.
Hybrid layers consisting of Fe oxide, Fe hydroxide, and nitrogen doped graphene-like platelets have been synthesized by an eco-friendly laser-based method for photocatalytic applications. The complex composite layers show high photodecomposition efficiency towards degradation of antibiotic molecules under visible light irradiation. The photodecomposition efficiency was investigated as a function of relative concentrations of base materials, Fe oxide nanoparticles and graphene oxide platelets used for the preparation of target dispersions submitted to laser irradiation. Although reference pure Fe oxide/Fe hydroxide layers have high absorption in the visible spectral region, their photodecomposition efficiency is negligible under the same irradiation conditions. The high photocatalytic decomposition efficiency of the nanohybrid layer, up to 80% of the initial antibiotic molecules was assigned to synergistic effects between the constituent materials, efficient separation of the electron-hole pairs generated by visible light irradiation on the surface of Fe oxide and Fe hydroxide nanoparticles, in the presence of conducting graphene-like platelets. Nitrogen doped graphene-like platelets contribute also to the generation of electron-hole pairs under visible light irradiation, as demonstrated by the photocatalytic activity of pure, reference nitrogen doped graphene-like layers. The results also showed that adsorption processes do not contribute significantly to the removal of antibiotic molecules from the test solutions. The decrease of the antibiotic concentration under visible light irradiation was assigned primarily to photocatalytic decomposition mechanisms.


Rare incidence of cholecystocolonic fistula and robotic-assisted surgical management.
We present a patient who was found to have a cholecystocolonic fistula during robotic cholecystectomy. The patient initially presented with Non-ST-elevation myocardial infarction (NSTEMI) and biliary obstruction. A delayed cholecystectomy was performed robotically after managing his Coronary Artery Disease (CAD) and relief of his biliary obstruction with endoscopic retrograde cholangiopancreatography (ERCP). Intraoperatively, a cholecystocolonic fistula, was found. This case report aims to highlight intraoperative management of the fistula and review the existing literature.


Asymmetric synthesis of N-bridged [3.3.1] ring systems by phosphonium salt/Lewis acid relay catalysis.
Optically pure pseudo-natural products (PNPs), particularly exemplified by azabicyclo[3.3.1]nonane molecules and their analogs provide an attractive platform for structure-activity relationship studies, and also lead new compound discovery in drug development. However, there are currently no examples of guiding catalytic asymmetric strategies available to construct such important PN-scaffolds, thus limiting their broad use. Here, we report a general and modular method for constructing these pseudo-natural N-bridged [3.3.1] ring systems via cascade process by bifunctional phosphonium salt/Lewis acid relay catalysis. A wide variety of substrates bearing an assortment of functional groups (59 examples) are compatible with this protocol. Other features include a [3 + 2] cyclization/ring-opening/Friedel-Crafts cascade pathway, excellent reactivities and stereoselectivities, easily available starting materials, step economy and scalability. The obtained enantioenriched products showed potential of preliminary anticancer activities. Insights gained from our studies are expected to advance general efforts towards the catalytic synthesis of challenging even unprecedented chiral PNPs, offering new opportunities for bioactive small-molecule discovery.


Bayesian inference for model-based segmentation of computed radiographs of the hand.
We present a method for medical image understanding by computer that uses model-based, hierarchical Bayesian inference to accurately segment imaged anatomy. A first application is a prototype system that automatically segments and measures symptoms of arthridities in hand radiographs. This is potentially useful in radiological diagnosis and tracking of arthridities. Key steps of the model-based, Bayesian inference approach are: (1) prediction of imagery features from 3D models of anatomy, parameterized by population statistics, (2) local image feature extraction in predicted sub-regions, and (3) the use of a probabilistic calculus to accrue results of image processing and image feature matching procedures in support or denial of hypotheses about the imaged anatomy. The prototype system for hand radiograph analysis accurately segments normal and somewhat degenerated hand anatomy. Results are shown of the ability of the automated system to 'fail soft', recognizing when segmentation is inadequate for accurate measurement. This self evaluation capability improves reliability of measurements for potential clinical use.


Effect of ATP inhibitors on the translocation of luminal membrane between cytoplasm and cell surface of transitional epithelial cells during the expansion-contraction cycle of the rat urinary bladder.
Movement of asymmetric membrane plaques between the cytoplasm and surface of luminal urothelial cells was investigated during artificially induced contraction and expansion of untreated and ATP-depleted urinary bladders of the rat. Estimations of surface area, volume, and number of discoidal vesicles per unit volume of cytoplasm were determined by morphometric examination of electron micrographs. These values were compared in luminal cells from bladders incubated in control media or in media containing 0.15 mM 2,4-dinitrophenol and 0.02 mM sodium arsenate. The ATP inhibitors had no apparent effect upon the contraction of apical cells that had been incubated in an expanded state. In contrast, after distension of poisoned, contracted bladders, the orientation of intermediate filaments and the densities of discoidal vesicles were similar to the condition characterized by contracted cells. The results indicated that the normal reorientation of filaments, coincident with cell distension, had been suppressed by ATP inhibitors. This, in effect, impeded the filament-mediated translocation of membrane plaques to the surface. The reduction of surface area along the luminal border forced many cells to compensate by separating at their lateral margins.


Endothelin B receptor mediates the endothelial barrier to T cell homing to tumors and disables immune therapy.
In spite of their having sufficient immunogenicity, tumor vaccines remain largely ineffective. The mechanisms underlying this lack of efficacy are still unclear. Here we report a previously undescribed mechanism by which the tumor endothelium prevents T cell homing and hinders tumor immunotherapy. Transcriptional profiling of microdissected tumor endothelial cells from human ovarian cancers revealed genes associated with the absence or presence of tumor-infiltrating lymphocytes (TILs). Overexpression of the endothelin B receptor (ET(B)R) was associated with the absence of TILs and short patient survival time. The ET(B)R inhibitor BQ-788 increased T cell adhesion to human endothelium in vitro, an effect countered by intercellular adhesion molecule-1 (ICAM-1) blockade or treatment with NO donors. In mice, ET(B)R neutralization by BQ-788 increased T cell homing to tumors; this homing required ICAM-1 and enabled tumor response to otherwise ineffective immunotherapy in vivo without changes in systemic antitumor immune response. These findings highlight a molecular mechanism with the potential to be pharmacologically manipulated to enhance the efficacy of tumor immunotherapy in humans.


New concept in swine wastewater treatment: development of a self-sustaining synergetic microalgae-bacteria symbiosis (ABS) system to achieve environmental sustainability.
Much attention has been paid to developing methods capable of synchronous removal of pollutants from swine wastewater. Due to the natural symbiotic interactions between microalgae and bacteria, the microalgae-bacteria symbiosis (ABS) system has been found to have potential for treating wastewater. However, the corresponding biological mechanisms in the ABS system and the role of dynamic microbial community evolution in pollutant removal systems remain poorly understood. Therefore, we investigate the potential of an ABS system for pollutant removal applications and analyze the bacterial consortium symbiotically combined with Chlorella sp. MA1 and Coelastrella sp. KE4. The NH4+-N and PO43--P removal efficiencies were significantly increased from 12.79% to 99.52% and 35.66% to 96.06% due to biotic interactions between the microalgae and bacteria. The abundance of bacterial taxa and genes related to oxidative stress, cell growth and nitrogen transfer were found to increase in response to photosynthesis, respiration and NH4+-N uptake. Furthermore, pathogen inactivation was induced via microalgae, co-driven by microbial succession under high dissolved oxygen conditions. In this microalgae-enhanced ABS system, the interactions between microalgae and bacteria are established for pathogens elimination and nitrogen cycling, verifying that the ABS system is an effective and environmentally sustainable swine wastewater treatment method.


Lipocalin type prostaglandin D-synthase: which role in male fertility?
Lipocalin type prostaglandin-D-synthase (L-PGDS), also called beta-trace, is an extracellular protein very abundant in compartments beyond blood-tissue barriers, such as the cerebrospinal fluid, the aqueous humor, the amniotic fluid and the seminal fluid. In the latter fluid the major function of L-PGDS does not seem to be the synthesis of prostaglandin D(2) (PGD(2)) from its precursor PGH(2), which is very unstable in aqueous solution. Instead, seminal L-PGDS, an important carrier of bile pigments, retinoids, thyroid hormones and essential fatty acids, would contribute to providing, beyond the blood-testis barrier, thyroid hormones and retinoids to the developing germ cells in the seminiferous tubules and the maturing spermatozoa in the epididymis.


An extended multi-locus molecular typing schema for Streptococcus pneumoniae demonstrates that a limited number of capsular switch events is responsible for serotype heterogeneity of closely related strains from different countries.
Streptococcus pneumoniae is a major cause of morbidity and mortality worldwide. Pneumococcal strains are classified according to their capsular serotype and through a Multi-Locus Sequence Typing schema (MLST) based on the sequencing of seven housekeeping genes. However, strains with a defined allelic profile (Sequence Type, ST) can have different serotypes, suggesting that the micro-evolution of the MLST lineages leads to a considerable degree of phenotypic variability. To better investigate the genetic diversity within these lineages, we set-up and then validated an extended molecular typing schema (96-MLST) based on the sequencing of ninety-six genomic loci. 96-MLST loci were designed within core-genes in a collection of 39 complete genomes of S. pneumoniae. None of the capsular genes was included in the schema. When tested on a collection of 69 isolates, 96-MLST was able to partition strains with the same ST and diverse serotypes into groups that were homogenous for capsular serotype, improving our understanding of the evolution of epidemiologically relevant lineages. Phylogenetic sequence analysis showed that the capsular heterogeneity of three STs that were sampled more extensively could be traced back to a limited number of capsular switch events, indicating that changes of serotype occur occasionally during the short term expansion of clones. Moreover, a geographical structure of ST156 was identified, suggesting that the resolution guaranteed by this method is sufficient for phylogeographic studies. In conclusion, we showed that an extended typing schema was able to characterize the expansion of individual lineages in a complex species such as S. pneumoniae.


Hsp20 and its cardioprotection.
The small heat shock protein Hsp20, also referred to as P20/HspB6, is expressed in the brain, stomach, liver, lung, kidney, blood, smooth muscle, skeletal muscle, and cardiac tissue. Although Hsp20 is not heat-inducible, several cellular signaling pathways appear to regulate its biologic functions. In recent years, tremendous advances have been made in elucidating the significance of Hsp20 in smooth muscle and its potential benefits on coronary vasculature. Of interest, recent findings have demonstrated that sustained beta-adrenergic stimulation results in expression and phosphorylation of cardiac Hsp20. Moreover, Hsp20 overexpression enhances cardiac function and renders cardioprotection against beta-agonist-mediated apoptosis and ischemia/reperfusion injury ex vivo and in vivo. This article reviews the new findings on translocation of Hsp20 in response to various stimuli and the multiple cellular targets of Hsp20, with special emphasis on its protective effects in the heart.


Hallmarks of tumor-associated microglia response to experimental U87 human glioblastoma xenograft.
Glioblastoma (GBM) is one of the deadliest primary brain neoplasm, heavily infiltrated with tumor-associated microglia/macrophages (TAM), which has received a great deal of interest. Bearing in mind that the number of peripheral macrophages by the 14th day is negligible, in our study TAM were referred to as microglia. Here we evaluated histopathological characterization of TAM and kinetics of their infiltration in U87 orthotopic GBM, a commonly used model in preclinical research. To mimic different stages of GBM growth, we evaluated three-time points. Our data showed that the highest areal density of TAM was 7 days after GBM inoculation, with ability to proliferate early after initiation of GBM growth. The areal density of TAM within the tumor correlated with GBM growth and proliferation. Moreover, microglia underwent substantial morphological changes upon exposure to GBM cells. A transition from ramified morphology in peritumoral area to ameboid shape with larger soma and shortened, thick branches in the tumor core was observed. Higher areal fraction of blood vessels also correlated with the areal density of TAM. Given these pro-invasive features of microglia, this GBM model represents a good basis for further testing microglia as a target and new strategy to fight with.


Glucocorticoids and the development of agonistic behaviour during puberty in male golden hamsters.
During puberty, the agonistic behaviour of male golden hamsters undergoes a transition from play fighting to adult aggression. Repeated exposure to social stress early in puberty accelerates this transition. The present study investigated the possible role of glucocorticoids on the maturation of agonistic behaviour. First, we compared serum cortisol levels following a 20-min restraint stress during early puberty, mid-puberty or adulthood. Across puberty, animals exhibited a two-fold increase in post-restraint cortisol levels. We also compared corticotrophin-releasing hormone (CRH) immunoreactive fibres projecting to the median eminence between animals in early puberty and adulthood. The CRH fibre density was two-fold greater in adults compared to juveniles. Furthermore, we investigated the effects of stress hormones on the maturation of agonistic behaviour. Male hamsters were injected daily with dexamethasone, a corticosteroid receptor type II agonist (0, 10 or 40 microg/100 g), early in puberty from postnatal day 31 (P-31) to P-36. When paired with a smaller and younger intruder on P-37, attack frequency did not differ between groups. However, dexamethasone-treated animals showed a dose-dependent decrease in the percentage of play-fighting attacks and an increase in the percentage of adult attacks. In summary, puberty can be described as a period of increasing hypothalamic-pituitary-adrenal activity in male golden hamsters. Moreover, increasing glucocorticoid levels influence the maturation of agonistic behaviour. These data shed new light on the neuroendocrine mechanisms that regulate the maturation of social behaviours during puberty.


Methodological quality of systematic reviews on sepsis treatments: A cross-sectional study.
Systematic reviews (SRs) offer updated evidence to support decision-making on sepsis treatments. However, the rigour of SRs may vary, and methodological flaws may limit their validity in guiding clinical practice. This cross-sectional study appraised the methodological quality of SRs on sepsis treatments. We searched MEDLINE, EMBASE, and Cochrane Database for eligible SRs on randomised controlled trials on sepsis treatments with at least one meta-analysis published between 2018 and 2023. We extracted SRs' bibliographical characteristics with a pre-designed form and appraised their methodological quality using AMSTAR (A MeaSurement Tool to Assess systematic Reviews) 2. We applied logistic regressions to explore associations between bibliographical characteristics and methodological quality ratings. Among the 102 SRs, two (2.0%) had high overall quality, while respectively four (3.9%), seven (6.9%) and 89 (87.3%) were of moderate, low, and critically low quality. Performance in several critical methodological domains was poor, with only 32 (31.4%) considering the risk of bias in primary studies in result interpretation, 22 (21.6%) explaining excluded primary studies, and 16 (15.7%) applying comprehensive searching strategies. SRs published in higher impact factor journals (adjusted odds ratio: 1.19; 95% confidence interval: 1.05 to 1.36) was associated with higher methodological quality. The methodological quality of recent SRs on sepsis treatments is unsatisfactory. Future reviewers should address the above critical methodological aspects. More resources should also be allocated to support continuous training in critical appraisal among healthcare professionals and other evidence users.


Something to despair: Gender differences in adverse childhood experiences among rural patients.
Existing research has demonstrated that patients in treatment for an opioid use disorder (OUD) have high rates of adverse childhood experiences (ACE) compared to community-based samples. While research has documented important gender differences in ACEs in patients with OUD receiving treatment in urban areas, research has not shown whether these findings would generalize to rural and Appalachian areas, which are known to have lower ACE scores. We conducted a secondary analysis of existing clinical data, utilizing intake assessment data from a rural Appalachian outpatient buprenorphine program. We restricted the sample to patients with an OUD who presented for treatment between June 2018 and June 2019 (n = 173). The clinical intake assessment included a modified 17-item ACE instrument that patients self-administered. More than half (54.3%) of patients reported having experienced 4+ categories of adverse childhood experiences. On average, females endorsed 4.5 categories of adverse experiences, whereas males endorsed 3.3 (p < 0.00); female patients were significantly more likely to have experienced sexual abuse (42.4% versus 10.6%, p < 0.00). Alarmingly, 25.9% of females and 8.2% of males reported being forced to have sex before age 18. Disproportionately high rates of childhood adversities, particularly among females, may partially explain despair in rural Appalachian areas. OUD treatment programs should conduct clinical assessments of trauma and integrate trauma-informed care into drug treatment, especially for female patients residing in rural Appalachia.


Systematic Studies on the Antioxidant Capacity and Volatile Compound Profile of Yellow Mealworm Larvae (T. molitor L.) under Different Drying Regimes.
The yellow mealworm (Tenebrio molitor L., Coleoptera: Tenebrionidae) is an edible insect and due to its ubiquitous occurrence and the frequency of consumption, a promising candidate for the cultivation and production on an industrial scale. Moreover, it is the first insect to be approved by EFSA 2021 following the Novel Food Regulation. Industrial production of mealworms necessitates optimized processing techniques, where drying as the first postharvest procedure is of utmost importance for the quality of the final product. The focus of the present study was to analyse the chemical composition, antioxidant capacity, volatile compound profile and colouring of mealworm larvae dried in various regimes (freeze-drying, microwave drying, infrared drying, rack-oven drying and high-frequency drying). Proximate composition and fatty acid profile were similar for all dried larvae. Freeze dried larvae were predominantly marked by lipid oxidation with significantly higher peroxide values, secondary/tertiary oxidation products in the headspace GC-MS profiles and lower antioxidant capacity. High-temperature treatment in the rack oven-and to some extent also infrared or microwave drying-led to mealworm larvae darkening and the appearance of volatile Maillard secondary products such as 2-methylpropanoic acid, 2-/3-methylbutanoic acid and alkylpyrazines. High-frequency drying as a new emerging technology in insect processing was the most cost-effective method with energy costs of solely 0.09 Є/kg T. molitor L. leading to final larval material characterized by both lipid oxidation and nonenzymatic Maillard-browning.


Management of large aggressive nonfunctional pituitary tumors: experimental medical options when surgery and radiation fail.
Pituitary adenomas are generally considered benign tumors; however, a subset of these tumors displays aggressive behavior and are not easily cured. The protocol for nonsurgical treatment of aggressive pituitary lesions is less standardized than that of other central nervous system tumors. Aggressive surgical treatment, radiation, dopamine agonists, antiangiogenic drugs, and other chemotherapeutics all have roles in the treatment of aggressive pituitary tumors. More studies are needed to improve outcomes for patients with aggressive pituitary tumors.


Use of goniometry to predict inadequate flexion-extension roentgenograms: a preliminary study.
Flexion-extension roentgenograms (FER) of the cervical spine are often inadequate because of limited range of motion (ROM). The purpose of this study was to determine the utility of goniometry to predict a patient's ability to achieve sufficient ROM to obtain adequate FER. We evaluated 65 consecutive blunt trauma patients undergoing evaluation by FER in the emergency department. Patients were evaluated by goniometry before performing FER. Adequate ROM was defined as flexion and extension of >30 degrees from neutral. Seventy-five percent of patients had adequate FER. All of these patients were predicted to have sufficient ROM by goniometry. Goniometry predicted limited ROM in 69% of patients who had inadequate FER. The positive predicative value of goniometry in predicting inadequate FER was 100%. The incidence of cervical spine injuries was 44% in patients with inadequate ROM by goniometry and 23.0% in patients with inadequate FER (versus 7.69% in patients with adequate FER). Goniometry accurately predicted those patients who were unable to achieve sufficient ROM for adequate FER. Patients with inadequate FER were at a higher risk for cervical spine injury compared with patients with adequate FER (23.0 versus 7.69%). Early identification of these patients will help limit the number of inadequate studies obtained and expedite evaluation of high-risk patients.


Atypical perifoveal exudative vascular anomalous complex (PEVAC) with multifocal and bilateral presentation.
To report an unusual case of multifocal and bilateral perifoveal exudative vascular anomalous complex (PEVAC) lesions in an otherwise healthy patient. A 62-year-old male with complaints of long-term progressive blurred vision in both eyes. There was no history of diabetes, arterial hypertension or inflammatory disease. Best-corrected visual acuity was 75 and 80 letters in his right eye (OD) and left eye (OS) respectively. Fundus examination showed three perifoveal isolated large aneurysmal lesions in his OD and an additional one in his OS, associated with smaller microaneurysms, haemorrhages and intraretinal exudation. On optical coherence tomography PEVAC appeared as a round lesions with a hyperreflective wall and lumen containing variably reflective material, typically surrounded by intraretinal fluid. Dye-based angiography demonstrated three and one well-defined large hyperfluorescent aneurysmal lesions in his OD and OS respectively, with no leakage. The optical coherence tomography angiography images showed flow signal within the intraretinal aneurysmal lesions. No anomalous flow signal in the outer retina and choriocapillaris was present. After one bilateral anti-vascular endothelial growth factor intravitreal injection no anatomical or functional improvement was observed, and no changes in the lesions or visual acuity were observed at 6 months follow-up. We describe an atypical case of PEVAC, an uncommon and poorly known macular disorder, with bilateral presentation and multifocal lesions in one eye. To our knowledge, this is the first reported case of bilateral PEVAC lesions. Hence, PEVAC should be included in the differential diagnosis of bilateral perifoveal aneurysmal lesions with macular edema.


Membrane tension modulates the effects of apical cholesterol on the renal epithelial sodium channel.
We used patch-clamp techniques and A6 distal nephron cells as a model to determine how cholesterol regulates the renal epithelial sodium channel (ENaC). We found that luminal methyl-beta-cyclodextrin (mbetaCD, a cholesterol scavenger) did not acutely affect ENaC activity at a previously used concentration of 10 mM: but significantly decreased ENaC activity both when the cell membrane was stretched and at a higher concentration of 50 mM: Luminal cholesterol had no effect on ENaC activity at a concentration of 50 microg/ml but significantly increased ENaC activity both when the cell membrane was stretched and at a higher concentration of 200 microg/ml. Confocal microscopy data indicate that membrane tension facilitates both mbetaCD extraction of cholesterol and A6 cell uptake of exogenous cholesterol. Together with previous findings that cholesterol in the apical membrane is tightly packed with sphingolipids and that stretch can affect lipid distribution, our data suggest that membrane tension modulates the effects of mbetaCD and cholesterol on ENaC activity, probably by facilitating both extraction and enrichment of apical cholesterol.


Calcium sensitivity and energetics of contraction in skinned smooth muscle of the guinea pig taenia coli at altered pH.
Calcium-sensitivity of contraction, force-velocity relation and ATP hydrolysis rate at different pH (6.2-7.8) were investigated in skinned smooth muscle preparations from the guinea pig taenia coli. Varied free-calcium levels were buffered by 4 mM BAPTA (1,2-bis(2-aminophenoxy)-ethane-N,N,N'N'-tetraacetic acid) which has calcium binding properties little affected by pH. A small increase of calcium-sensitivity of contraction was seen at pH 6.2 compared to 6.9 and 7.8 (ED50 shift of about 0.15 pCa units). The isometric force and Vmax in fibres activated either by calcium or by thiophosphorylation of the myosin light chains were each reduced by about 15% at pH 6.2 compared to 6.9 and 7.8. Following an isotonic quick release the shortening velocity decreases with time. This effect was more pronounced at pH 6.2 than at pH 6.9 or 7.8. The ATP hydrolysis rates in relaxed and thiophosphorylated fibres were essentially unaffected by alteration in pH between 6.2 and 7.8. Due to the lower force, energetic cost of force maintenance was thus somewhat increased at pH 6.2. These results suggest that pH alteration between 6.2 and 7.8 have effects on the properties of the contractile machinery of the smooth muscle in the skinned guinea pig taenia coli. The effects are however small and therefore probably of little functional importance over a pH range which should cover most cases of intracellular pH alteration under physiological or pathophysiological conditions.


Sleep disturbances among medical workers during the outbreak of COVID-2019.
The outbreak of Corona Virus Disease-2019 (COVID-19) has posed unprecedented pressure and threats to healthcare workers in Wuhan and the entire country. To assess the effect of the COVID-19 outbreak on the sleep quality of healthcare workers in a children's healthcare centre in Wuhan. A cross-sectional, anonymized, self-reported questionnaire survey was conducted at the Children's Healthcare Centre of Renmin Hospital, Wuhan University, Wuhan, China. The questionnaire consisted of three parts, including socio-demographic characteristics and COVID-19 epidemic-related factors, the Pittsburgh sleep quality index (PSQI), and Zung's self-rating anxiety scale (SAS) and self-rating depression scale (SDS). In total, 47 out of 123 (38%) participants with PSQI scores > 7 were identified as having sleep disturbance. A logistic regression analysis showed that sleep disturbance was independently associated with being an only child (adjusted odds ratio (OR) and 95% confidence interval (CI) 3.40 (1.21-9.57), P < 0.05), exposure to COVID-19 patients (adjusted OR and 95% CI 2.97 (1.08-8.18), P < 0.05) and depression (adjusted OR and 95% CI 2.83 (1.10-7.27), P < 0.05). We observed that, during the outbreak of COVID-19, sleep disturbance was highly prevalent among paediatric healthcare workers, and sleep disturbance was independently associated with being an only child, exposure to COVID-19 patients and depression. Therefore, more mental health services are required for front-line paediatric healthcare workers in Wuhan.


The contribution of environmental cues to cross-tolerance between ethanol and pentobarbital.
The contribution of Pavlovian conditioning of environmental cues has been studied in relation to tolerance to ethanol-induced hypothermia and cross-tolerance to pentobarbital. Two groups of 12 male Sprague-Dawley rats were exposed every other day to a distinctive set of environmental cues paired with an IP injection of either ethanol 2.5 g/kg or an equivalent volume of isotonic saline. On alternating non-drug days, both groups received saline in the animal room. When they were tested for tolerance to the hypothermic effect of ethanol 2.5 g/kg and cross-tolerance to pentobarbital 25 mg/kg in each environment, tolerance and cross-tolerance in the ethanol-treated group were significantly more pronounced in the ethanol-paired environment than in the saline-paired environment. This indicates the importance of a conditional factor in tolerance and cross-tolerance in this paradigm. Determination of blood levels of ethanol and pentobarbital at various times after injection indicated that conditioned tolerance and cross-tolerance can be explained in part by dispositional factors.


Kinetic parameters and the course of the disease in breast cancer.
The correlation between the labeling index (LI) of the primary mammary tumor and the course of the disease after initial treatment was studied prospectively on 128 patients. The surgical specimens of breast tumors were incubated in vitro with tritiated thymidine and autoradiographies were performed. Patients were treated by a simple mastectomy and axillary lymph nodes dissection; patients in whom one or more lymph nodes were found to be involved received postoperative radiotherapy. None of the patients received adjuvant chemotherapy. As the LIs were not known at the time of treatment, their values did not influence the choice of therapy. The follow-up period is greater than six years for all patients. The higher the LI, the shorter were the time intervals from initial treatment to first relapse or from first relapse to death. Moreover, significant correlations were found between the LI and the relapse-free survival and the survival rates. The proportion of relapses was particularly small in the group with the low LI. The shape of the curve suggests that the outcome in this group will be better than that in the group with a high or a median LI. The LI kept its prognostic value after multiple adjustments for other prognostic factors such as the staging, the size of the tumor, the number of metastasis bearing axillary lymph nodes, the presence of an inflammatory reaction, and hormonal status. The LI is significantly correlated with the histologic grading and in particular with its mitotic components. Thus, proliferative activity assessed by LI or the mitotic index appears to provide significant independent prognostic information.


[Patient simulation for hand therapy in an anesthesiologist after an occupational injury: A case study].
We described the use of clinical simulation for hand therapy in an anesthesiologist that accidentally suffered from entrapment with the surgical table in the right thumb and underwent a partial toe-to-hand autograft. At week 14 after surgery, the patient practiced anesthetic tasks and clinical scenarios using a patient simulator instead undergoing a regular occupational therapy regimen. Quantifiable physical, functional and psychological measures improved during and after the simulation intervention, and there was no decline one month after the patient returned to work. The use of clinical simulation as part of the rehabilitation process of an anesthesiologist after hand injury contributed to improving the range of motion, strength, sensibility, and functional tests. Overall, it played an important role in determining the worker's potential to withstand the demands of anesthesia practice.


Caregiver Depressive Symptoms and Primary Medication Nonadherence in Children With Asthma.
The purpose of this study was to identify risk factors for primary medication nonadherence among low-income minority children with persistent asthma. Data were from an environmental control and educational intervention for children with uncontrolled asthma who were treated in the emergency department for an asthma exacerbation. Presence or absence of pharmacy records for child asthma medications was the outcome of interest. A range of sociodemographic, health, and psychosocial measures were included in the binary logistic regression. Of the 222 youths (mean age = 6.3 years; 93.7% Black), 25 (11.3%) lacked pharmacy records of asthma medications. For every 1-point increase in caregiver depressive symptoms, the odds of the child having a pharmacy record declined by 5% (odds ratio = 0.95; p = .012). Providers should systematically assess and monitor caregiver depressive symptoms as a potential contributing factor for primary medication nonadherence in low-income minority children with persistent, uncontrolled asthma.


Reducing short term suicide risk after hospitalization: A randomized controlled trial of the Collaborative Assessment and Management of Suicidality.
This study compared the "next day appointment" (NDA) use of the Collaborative Assessment and Management of Suicidality (CAMS) to treatment as usual (TAU) for individuals discharged from the hospital following a suicide-related crisis. We hypothesized that CAMS would significantly reduce suicidal thoughts and behaviors as well as improve psychological distress, quality of life/overall functioning, treatment retention and patient satisfaction. Participants were 150 individuals who had at least one lifetime actual, aborted, or interrupted attempt and were admitted following a suicide-related crisis. There were 75 participants in the experimental condition who received adherent CAMS and 75 participants who received TAU. Suicidal thoughts and behaviors, psychological distress, and quality of life/overall functioning were assessed at baseline and at 1, 3, 6, and 12 months post-baseline. Treatment retention and patient satisfaction were assessed at post-treatment. Participants in both conditions improved from baseline to 12 months but CAMS was not superior to TAU for the primary outcomes. A small but significant improvement was found in probability of suicidal ideation at 3 months favoring TAU and amount of suicidal ideation at 12 months favoring CAMS. CAMS participants experienced less psychological distress at 12 months compared to baseline. The study was limited by only one research clinic, lower than expected recruitment, and imbalance of suicidal ideation at baseline. All participants improved but CAMS was not more effective than TAU. The NDA clinic was feasible and acceptable to clients and staff in both conditions and future research should investigate its potential benefit.


The distinctive significance of analgesic drugs and olfactory stimulants on learned pain in mice.
Chronic pain is often intractable to analgesics, and in animals it involves a conditioned nociceptive response (CR) - learned pain. The neural pathways of nociception and olfactory function in the brain overlap. The influence of olfactory stimuli on acute pain has been studied in some depth in animal and human models, but the influence of olfactory stimuli on learned pain has not been understood. We examined the effects of analgesic drugs and olfactory stimulants (preferred or repellent odor) on acute pain, the unconditioned nociceptive response (UCR) and the CR in mice. The CR was provoked by repeated injection of formalin into the hind-paw in animals in the same context, which elicited the typical pain behaviors of paw licking (including biting). The analgesic drugs acetaminophen, fentanyl, gabapentin and fluvoxamine diminished the UCR but did not affect the CR. In contrast, the preferred odor reduced both the UCR and the CR. Our findings suggest that, like chronic pain, the CR is resistant to analgesic drugs and that preferred odor suppress the neural pathways that mediate the CR of pain perception.


The effect of osteopathic medicine on pain in musicians with nonspecific chronic neck pain: a randomized controlled trial.
Nonspecific chronic neck pain (cNP) is common in adult violinists and violists and is often treated with osteopathic medicine (OM), although the effectiveness of this treatment has not been determined to date. This study aimed to evaluate the effectiveness and safety of OM in adult violinists and violists with cNP. In a two-armed randomized controlled single-center open trial, adult violinists and violists, including music students, with cNP (⩾12 weeks) were randomized to either five individualized OM sessions (OM group) or to no intervention (control group, CG) in the outpatient clinic for integrative medicine, Charité - Universitätsmedizin Berlin, Germany. All patients received a musicians' medicine consultation and paracetamol on demand. The primary outcome parameter was the neck pain intensity on a visual analog scale (VAS, 0-100 mm, 0 = no pain, 100 = worst imaginable pain) after 12 weeks. Secondary outcomes included neck pain disability (Neck Disability Index, NDI, 0-100%) after 12 weeks. The last follow-up visit was after 52 weeks. Statistical analysis included analysis of covariance adjusted for respective baseline value. Altogether, 62 outpatients were included [OM group (n = 28), CG (n = 34); 81% female; mean age, 41.6 ± 11.1 years; mean baseline neck pain, 55.9 ± 11.6 mm]. After 12 weeks, OM was associated with an improvement in the OM group versus the CG in neck pain on the VAS [14.6 mm (95% confidence interval 8.0; 21.2) versus 40.8 mm (34.7; 46.9), p < 0.001, Cohen's d = 1.4], and neck pain disability as determined by the NDI [8.8% (6.7; 10.8) versus 17.2% (15.3; 19.1), p < 0.001]. Some improvements were maintained until 52 weeks of follow-up. No serious adverse events were observed. The results of this study suggest that OM might be effective in reducing pain intensity in adult violinists and violists with nonspecific cNP. Further studies should investigate the efficacy of OM in comparison with a sham procedure and with other effective therapy methods in high-quality multicenter trials. WHO Trial Registration https://apps.who.int/trialsearch/NoAccess.aspx?aspxerrorpath=/trialsearch/Trial2.aspx by German Clinical Trials Register DRKS00009258, Universal Trial Number (UTN): U1111-1173-5943.


Reliability and Validity of the Korean Version of the Ask Suicide-Screening Questions (ASQ).
The Ask Suicide-Screening Questions (ASQ) tool is a simple suicide screening tool developed to screen patient suicide risk (SR). The purpose of this study was to verify the reliability and validity of the ASQ tool in hospitalized patients. The internal consistency and test-retest reliability of the South Korean version of the ASQ tool were verified in 99 hospitalized patients admitted to a tertiary medical institution in Seoul. To verify the correlations and validity of each convergence with other scales, the Mini-International Neuropsychiatric Interview (MINI), Patient Health Questionnaire-9 (PHQ-9), Generalized Anxiety Disorder-7 (GAD-7), and Satisfaction with Life Scale (SWLS) were also conducted to determine convergent and discriminant validity. Then, the receiver operating characteristic (ROC) curve diagnosis values for suicide and depression levels with the highest correlations were analyzed. As a result, Cronbach's alpha was 0.826, and when each item was removed sequentially, Cronbach's alpha ranged from 0.736-0.840, showing stable internal consistency. Most of the corrected item-total correlation were over 0.500; however, a relatively low correlation was shown for the fourth and fifth questions, which had values of 0.429 and 0.410, respectively. The test-retest reliability was 0.830, and the MINI and PHQ-9 showed high values of 0.872 and 0.672, respectively. The area under the curve (AUC) according to the ASQ diagnosis value was also the highest for the MINI (0.936). The validity and reliability of the South Korean version of the ASQ tool were demonstrated. Through this validation, the ASQ tool can be used for simple suicide risk screening (SRS) in hospitalized patients.


Uremic pruritus: roles of parathyroid hormone and substance P.
Most patients receiving maintenance hemodialysis have pruritus, but its underlying mechanism remains unknown. Secondary hyperparathyroidism is another common problem in these patients, but its role in uremic pruritus is controversial. Capsaicin can deplete substance P from the peripheral neurons and is known to be effective in the treatment of pain and itching. Our purpose was to evaluate the role of parathyroid hormone (PTH) and substance P in uremic pruritus and to elucidate the underlying mechanisms. The study contained two phases. In phase I, we analyzed the correlation between the intensity of itching and serum levels of intact PTH. In phase II, patients with moderate to severe pruritus were placed into two groups: one with high PTH levels and one with low levels. A double-blind, placebo-controlled study of capsaicin 0.025% cream was conducted in phase II. Serum levels of intact PTH did not correlate with the intensity of pruritus and did not significantly change during treatment with capsaicin or placebo. Capsaicin was significantly more effective in alleviating uremic pruritus than the placebo, and no serious side effects were noted. Uremic pruritus is not related to PTH. Substance P may act as a neurotransmitter in uremic pruritus and topical capsaicin can be used in the treatment of localized pruritus.


Inhibitory role of Ser-425 of the alpha1 2.2 subunit in the enhancement of Cav 2.2 currents by phorbol-12-myristate, 13-acetate.
Voltage-gated calcium channels (Ca(v)) 2.2 currents are potentiated by phorbol-12-myristate, 13-acetate (PMA), whereas Ca(v) 2.3 currents are increased by both PMA and acetyl-beta-methylcholine (MCh). MCh-selective sites were identified in the alpha(1) 2.3 subunit, whereas the identified PMA sites responded to both PMA and MCh (Kamatchi, G. L., Franke, R., Lynch, C., III, and Sando, J. J. (2004) J. Biol. Chem. 279, 4102-4109; Fang, H., Franke, R., Patanavanich, S., Lalvani, A., Powell, N. K., Sando, J. J., and Kamatchi, G. L. (2005) J. Biol. Chem. 280, 23559-23565). The hypothesis that PMA sites in the alpha(1) 2.2 subunit are homologous to the PMA-responsive sites in alpha(1) 2.3 subunit was tested with Ser/Thr --> Ala mutations in the alpha(1) 2.2 subunit. WT alpha(1) 2.2 or mutants were expressed in Xenopus oocytes in combination with beta1b and alpha2/delta subunits. Inward current (I(Ba)) was recorded using Ba(2+) as the charge carrier. T422A, S1757A, S2108A, or S2132A decreased the PMA response. In contrast, S425A increased the response to PMA, and thus, it was considered an inhibitory site. Replacement of each of the identified stimulatory Ser/Thr sites with Asp increased the basal current and decreased the PMA-induced enhancement, consistent with regulation by phosphorylation at these sites. Multiple mutant combinations showed (i) greater inhibition than that caused by the single Ala mutations; (ii) that enhancement observed when Thr-422 and Ser-2108 are available may be inhibited by the presence of Ser-425; and (iii) that the combination of Thr-422, Ser-2108, and either Ser-1757 or Ser-2132 can provide a greater response to PMA when Ser-425 is replaced with Ala. The homologous sites in alpha(1) 2.2 and alpha(1) 2.3 subunits seem to be functionally different. The existence of an inhibitory phosphorylation site in the I-II linker seems to be unique to the alpha(1) 2.2 subunit.


Oral supplementation with sulodexide inhibits neo-angiogenesis in a rat model of peritoneal perfusion.
Peritoneal dialysis (PD) is associated with functional and morphological alterations of the peritoneal membrane (PM). It is hypothesized that vascular endothelial growth factor (VEGF) plays a role in this process. Sulodexide is a glycosaminoglycan with effects on vascular biology. Therefore, the impact of oral sulodexide on PM function and morphology in a rat model of peritoneal perfusion was evaluated. Rats received 10 mL peritoneal dialysate fluid (PDF) twice daily via a tunnelled PD catheter. The test-PD group (Sul) received 15 mg/kg/day oral sulodexide versus none in the control-PD group (Con). A third group received no PDF (Sham). After 12 weeks, a peritoneal equilibration test was performed and the PM was sampled. Neo-angiogenesis was evaluated using immunostaining with von Willebrand, and epithelial-to-mesenchymal transition (EMT) using co-localization of cytokeratin and α-smooth muscle actin. VEGF was determined in the dialysate by enzyme-linked immunosorbent assay. PD induced loss of ultrafiltration, also in the sulodexide group. Creatinine and glucose transport were better preserved, and sodium dip was more pronounced in the sulodexide group versus control. Submesothelial thickness, neo-angiogenesis and EMT were more pronounced in the Con versus Sul versus Sham group. VEGF in the dialysate, corrected for diffusion was higher in Con and Sul versus Sham. Oral sulodexide administration diminishes neo-vascularization, submesothelial thickening and EMT induced by exposure to PDF in a rat model. As there was no difference in VEGF at the protein level in the dialysate, we hypothesize that oral sulodexide inhibits VEGF locally by binding.


Multi-modal MRI of hippocampal morphometry and connectivity after pediatric severe TBI.
This investigation explores memory performance using the California Verbal Learning Test in relation to morphometric and connectivity measures of the memory network in severe traumatic brain injury. Twenty-two adolescents with severe traumatic brain injury were recruited for multimodal MRI scanning 1-2 years post-injury at 13 participating sites. Analyses included hippocampal volume derived from anatomical T1-weighted imaging, fornix white matter microstructure from diffusion tensor imaging, and hippocampal resting-state functional magnetic resonance imaging connectivity as well as diffusion-based structural connectivity. A typically developing control cohort of forty-nine age-matched children also underwent scanning and neurocognitive assessment. Results showed hippocampus volume was decreased in traumatic brain injury with respect to controls. Further, hippocampal volume loss was associated with worse performance on memory and learning in traumatic brain injury subjects. Similarly, hippocampal fornix fractional anisotropy was reduced in traumatic brain injury with respect to controls, while decreased fractional anisotropy in the hippocampal fornix also was associated with worse performance on memory and learning in traumatic brain injury subjects. Additionally, reduced structural connectivity of left hippocampus to thalamus and calcarine sulcus was associated with memory and learning in traumatic brain injury subjects. Functional connectivity in the left hippocampal network was also associated with memory and learning in traumatic brain injury subjects. These regional findings from a multi-modal neuroimaging approach should not only be useful for gaining valuable insight into traumatic brain injury induced memory and learning disfunction, but may also be informative for monitoring injury progression, recovery, and for developing rehabilitation as well as therapy strategies.


Induction of aromatic ring: cleavage dioxygenases in Stenotrophomonas maltophilia strain KB2 in cometabolic systems.
Stenotrophomonas maltophilia KB2 is known to produce different enzymes of dioxygenase family. The aim of our studies was to determine activity of these enzymes after induction by benzoic acids in cometabolic systems with nitrophenols. We have shown that under cometabolic conditions KB2 strain degraded 0.25-0.4 mM of nitrophenols after 14 days of incubation. Simultaneously degradation of 3 mM of growth substrate during 1-3 days was observed depending on substrate as well as cometabolite used. From cometabolic systems with nitrophenols as cometabolites and 3,4-dihydroxybenzoate as a growth substrate, dioxygenases with the highest activity of protocatechuate 3,4-dioxygenase were isolated. Activity of catechol 1,2- dioxygenase and protocatechuate 4,5-dioxygenase was not observed. Catechol 2,3-dioxygenase was active only in cultures with 4-nitrophenol. Ability of KB2 strain to induce and synthesize various dioxygenases depending on substrate present in medium makes this strain useful in bioremediation of sites contaminated with different aromatic compounds.


Evaluation of preoperative investigations in patients admitted for ovarian primary cytoreductive surgery.
Consistent with universally established practice, it has been customary in our unit to subject patients with clinically suspected or biopsy proven ovarian cancer to a large number of preoperative investigations. This is in order to determine metastases, surgical strategy, and exclusion of pelvic kidney. This study presents a comparison of the preoperative ultrasonography, computerized tomography, intravenous pyelography, chest X-ray, liver and bone scintigraphy, and barium enema results performed in 100 cases with the operative findings. These investigations were found to have marginal value in determining extent of disease, upper gastrointestinal metastatic deposits, and the need for or extent of bowel resection. It is concluded that such a standard workup, which is time-consuming and distressing for an already anxious patient, is not cost effective for a surgical procedure which is ultimately determined at laparotomy.


Bile acids and their receptors during liver regeneration: "Dangerous protectors".
Tissue repair is orchestrated by a finely tuned interplay between processes of regeneration, inflammation and cell protection, allowing organisms to restore their integrity after partial loss of cells or organs. An important, although largely unexplored feature is that after injury and during liver repair, liver functions have to be maintained to fulfill the peripheral demand. This is particularly critical for bile secretion, which has to be finely modulated in order to preserve liver parenchyma from bile-induced injury. However, mechanisms allowing the liver to maintain biliary homeostasis during repair after injury are not completely understood. Besides cytokines and growth factors, bile acids (BA) and their receptors constitute an insufficiently explored signaling network during liver regeneration and repair. BA signal through both nuclear (mainly Farnesoid X Receptor, FXR) and membrane (mainly G Protein-coupled BA Receptor 1, GPBAR-1 or TGR5) receptors which distributions are large in the organism, and which activation elicits a wide array of biological responses. While a number of studies have been dedicated to FXR signaling in liver repair processes, TGR5 remains poorly explored in this context. Because of the massive and potentially harmful BA overload that faces the remnant liver after partial ablation or destruction, both BA-induced adaptive and proliferative responses may stand in a central position to contribute to the regenerative response. Based on the available literature, both BA receptors may act in synergy during the regeneration process, in order to protect the remnant liver and maintain biliary homeostasis, otherwise potentially toxic BA overload would result in parenchymal insult and compromise optimal restoration of a functional liver mass.


NRF2 mediates γ-globin gene regulation through epigenetic modifications in a β-YAC transgenic mouse model.
Sickle cell disease is an inherited hemoglobin disorder that affects over 100,000 people in the United States causing high morbidity and early mortality. Although new treatments were recently approved by the FDA, only one drug Hydroxyurea induces fetal hemoglobin expression to inhibit sickle hemoglobin polymerization in red blood cells. Our laboratory previously demonstrated the ability of the NRF2 activator, dimethyl fumarate to induce fetal hemoglobin in the sickle cell mouse model. In this study, we investigated molecular mechanisms of γ-globin gene activation by NRF2. We observed the ability of NRF2 to modulate chromatin structure in the human β-like globin gene locus of β-YAC transgenic mice during development. Furthermore, an NRF2/TET3 interaction regulates γ-globin gene DNA methylation. These findings provide potential new molecular targets for small molecule drug developed for treating sickle cell disease.