[Structural and functional changes of endothelium of heart's vessels of old rats according to immunistochemical studies.]
The aim of the work is to investigate the morphofunctional changes of the vascular endothelium in different parts of the heart of aging rats using immunohistochemical detection of Willebrand factor. Reactive, dystrophic and pathological changes of endotheliocytes in different parts of the heart of old (18-23 months) rats were first identified using an immunohistochemical marker vWF. They are most expressed in the endothelium of the arterial vessels of the aortic root, coronary arteries of the epicardium, and myocardial capillaries. In this work, desquamation of endothelial cells into the blood, death of capillaries in the myocardium, an increase in the number of sinusoidal vessels, their mummification, the formation of lacunae or cisterns filled with blood were found. It has been established that the secretory activity of endotheliocytes increases with aging. It is established that the products of protein metabolism, pigment, Weibel-Palade body and various sizes of blood clots accumulate in the cavity subaroundal cone of heart in old rats. Pigment structures were also found in the valves and the fibrous ring. The data obtained are of great diagnostic value.


Older Adult and Family Caregiver Perspectives on Engagement in Primary Care.
The purpose of the current in-depth qualitative study was to explore the experiences of older adults and family caregivers in primary care. Twenty patients and caregivers from six Comprehensive Primary Care Plus (CPC+) practices' Patient and Family Advisory Councils within a large academic health system participated in telephone interviews from December 2018 to May 2019. Participants were mostly women (60%), with an average age of 71 years and nine chronic conditions. Transcripts were coded using conventional content analysis. Two key themes emerged related to person-centered care (PCC): Engagement in Health Care and Patient-Provider Relationship. Engagement in health care was defined by participants as: being proactive, centering on patient goals in treatment discussions, adherence, and self-triaging. Approximately all participants discussed the importance of the relationship and interactions with their provider as influencing their engagement. The identified themes offer recommendations for further improvement of primary PCC. [Journal of Gerontological Nursing, 48(11), 7-13.].


Fabrication, in-silico, in-vitro, and in-vivo characterization of transferrin-targeted micelles containing cisplatin and gadolinium for improved theranostic applications in lung cancer therapy.
The targeted delivery of therapeutic and imaging agents is quite challenging in lung cancer therapy. Thus, lung cancer causes high mortality across the world. Herein, we developed TPGS-PF127 micelles containing cisplatin (CDDP) as a model anticancer drug and gadolinium (Gd) as a diagnostic agent by a slightly modified solvent casting method, further, the surface of the micelles was modified using TPGS-transferrin (TPGS-Tf) conjugate to improve targeted delivery of micelles to the lung cancer cells. Prior to this, the binding affinity of Tf over TfR (1E7U) and TfR (1E8W) was investigated with the help of in-silico studies. In-silico results showed good docking scores -7.8 and -7.2 kcal/mol of Tf -ligand towards 1E8W and 1E7U respectively promoting PI3K inhibition. Micelles have shown an average particle size range of 80-200 nm and have shown spherical morphology. The encapsulation efficiency of cisplatin (CDDP) in the CPT, CGPT, and CGPT-Tf micelles ranged from 75.63 % ± 1.58 % to 85.07 % ± 2.65 %. Furthermore, the encapsulation efficiency of gadolinium (Gd) in the CGPT and CGPT-Tf micelles was found to be 67.50 ± 0.32 % and 62.52 ± 0.52 %, respectively. CGPT-Tf micelles exhibited sustained release fashion for CDDP up to 48 h in physiological conditions. In the cytotoxicity study, CGPT-Tf micelles achieved higher cytotoxicity and caused a more antiproliferative effect in A549 cells compared to a commercial CDDP injection (Ciszest 50), after 24 h of treatment. Furthermore, the pharmacokinetic studies have proven the pharmacological effectiveness of developed CGPT-Tf micelles by achieving higher Cmax, Tmax, t1/2, and MRT of CDDP in systemic circulation compared to its counterparts and Ciszest 50. In lung theranostic observations, a higher internalization of Gd was noted in CGPT-TF compared to free Gd. The biochemical studies have proved the biocompatibility of developed micelles formulations by showing no sign of toxicity in the lungs. The developed micelles have great potential to be utilized in treating and diagnosing a wide variety of cancers.


Initial docking of ER-derived vesicles requires Uso1p and Ypt1p but is independent of SNARE proteins.
ER-to-Golgi transport in yeast may be reproduced in vitro with washed membranes, purified proteins (COPII, Uso1p and LMA1) and energy. COPII coated vesicles that have budded from the ER are freely diffusible but then dock to Golgi membranes upon the addition of Uso1p. LMA1 and Sec18p are required for vesicle fusion after Uso1p function. Here, we report that the docking reaction is sensitive to excess levels of Sec19p (GDI), a treatment that removes the GTPase, Ypt1p. Once docked, however, vesicle fusion is no longer sensitive to GDI. In vitro binding experiments demonstrate that the amount of Uso1p associated with membranes is reduced when incubated with GDI and correlates with the level of membrane-bound Ypt1p, suggesting that this GTPase regulates Uso1p binding to membranes. To determine the influence of SNARE proteins on the vesicle docking step, thermosensitive mutations in Sed5p, Bet1p, Bos1p and Sly1p that prevent ER-to-Golgi transport in vitro at restrictive temperatures were employed. These mutations do not interfere with Uso1p-mediated docking, but block membrane fusion. We propose that an initial vesicle docking event of ER-derived vesicles, termed tethering, depends on Uso1p and Ypt1p but is independent of SNARE proteins.


Effectiveness and clinical application of multidisciplinary combined exercise and nutrition intervention for sarcopenic older adults with metabolic syndrome: study protocol for a multicentre randomised controlled trial.
Among chronic diseases affecting older adults, metabolic syndrome (MetS) is known to be closely related to sarcopenia. Insulin resistance may play a key role in the increased frequency of sarcopenia associated with metabolic disorders. To date, an exercise-nutrition combined intervention has been the treatment of choice for sarcopenia. However, trials of combined interventions for individuals with sarcopenia and MetS are still lacking. This study aims to develop and conduct a standardised intervention, named the Multidisciplinary combined Exercise and Nutrition inTervention fOR Sarcopenia (MENTORS), for sarcopenic older patients with MetS. This multicentre, randomised controlled trial includes 168 community-dwelling older adults with sarcopenia and MetS. The 12-week MENTORS comprises an exercise intervention consisting of an introductory phase (3 weeks; twice-weekly visits), an expanded phase (3 weeks; twice-weekly visits) and a maintenance phase (6 weeks; once-weekly visits); and a nutrition intervention tailored to the nutritional status of individual subjects. Outcomes will be measured at 0-week, 12-week and 24-week postintervention. The data will be analysed using the intention-to-treat and per-protocol principle. Before screening, all participants will be provided with oral and written information. Ethical approval has already been obtained from all participating hospitals. The study results will be disseminated in peer-reviewed publications and conference presentations. NCT04948736.


Local inverse tone curve learning for high dynamic range image scalable compression.
This paper presents a scalable high dynamic range (HDR) image coding scheme in which the base layer is a low dynamic range version of the image that may have been generated by an arbitrary tone mapping operator (TMO). No restriction is imposed on the TMO, which can be either global or local, so as to fully respect the artistic intent of the producer. Our method successfully handles the case of complex local TMOs thanks to a block-wise and non-linear approach. A novel template-based interlayer prediction (ILP) is designed in order to perform the inverse tone mapping of a block without the need to transmit any additional parameter to the decoder. This method enables the use of a more accurate inverse tone mapping model than the simple linear regression commonly used for block-wise ILP. In addition, this paper shows that a linear adjustment of the initially predicted block can further improve the overall coding performance by using an efficient encoding scheme of the scaling parameters. Our experiments have shown an average bitrate saving of 47% on the HDR enhancement layer, compared with the previous local ILP methods.


[Simulation of diabetes mellitus in rats: Latent and manifest forms].
The paper is concerned with the investigation of problems of the etiology and pathogenesis of diabetes mellitus and simulation of this disease in animals in order to study its preclinical stages. Experiments were performed on adult male rats using i.v. GTT, a radioimmunoassay for determination of blood insulin, immunoenzymatic detection of autoantibodies to pancreatic islet cell surface, and determination of complement dependent cytotoxicity. Fractionated intraperitoneal administration of subdiabetic doses of streptozocin was shown to cause the destruction of the insular apparatus in rats with the involvement of the immune system. Five injections of B-cytotoxin (40 mg/kg) caused the development of manifest diabetes mellitus, two injections led to a decrease in function of the insular apparatus and the appearance of autoantibodies to the surface of islet cells with cytotoxic features. Problems of the pathogenetic role of factors of humoral immunity in the development of type I diabetes mellitus are under discussion.


Adolescent alcohol use and injury. A summary and critical review of the literature.
Survey research indicates that alcohol use and misuse by adolescents is prevalent worldwide and has been associated with multiple negative health, social, and economic consequences. Physical injury is one of the negative consequences of alcohol use that appears to be on the rise among adolescents. A retrospective review was conducted of published data currently available regarding alcohol use and injury among adolescents. Studies were reviewed if 1) the sample included adolescents between the ages of 13 and 19 years, 2) the study site was a medical setting, and 3) data were collected regarding alcohol ingestion. Data indicate that rates of adolescent alcohol use range from 5% among general emergency department (ED) admissions to nearly 50% among trauma admissions. Alcohol-positive adolescents are more likely than alcohol-negative adolescents to be injured, have a prior history of injury, require trauma service care, and have injury complications. One-third to one-half of alcohol-positive adolescents are referred for or receive intervention related to their alcohol use. Alcohol use by adolescents is associated with increases in severity of injury and cost of medical treatment. Screening of adolescent trauma unit admissions for alcohol use might be justified based on the literature. Optimal methods of screening, identification, and brief intervention for alcohol abusing adolescents within the medical setting are discussed.


[MEASURING THE EFFECT OF MULTI-SENSORY STIMULATION IN THE SNOEZELEN ROOM ON SLEEP QUALITY OF ALZHEIMER PATIENTS USING ACTIGRAPH].
The most common cause of dementia is Alzheimer's disease. The major manifestation of the disease is the cognitive impairment which appears at the onset of the disease. In addition to the cognitive impairment there are behavioral dysfunctions such as apathy, anxiety, depression and sleep disturbances. The treatment for the manifestations of Alzheimer is currently pharmacological and behavioral. One of the newest behavioral treatments for Alzheimer is the multi-sensory treatment using the Snoezelen room. The study group included 16 hospitalized Alzheimer patients. A device called the ActiGraph, which reads movement level, was placed on the subjects' non-dominant wrist. The measurements took place continually for five nights: two nights before snoezelen treatment, the day of treatment and two nights after the treatment. This protocol was repeated after a week of rest. The results showed that snoezelen treatment has a positive effect on the quality of sleep during the first week but not on the second week. Snoezelen treatment should be considered as part of the treatment regimen of Alzheimer patients, in addition to the pharmacological treatments in order to improve their quality of sleep and quality of life. Larger sample size and longer periods of time are needed to confirm the effectiveness of the treatment.


Acute hypoxia selectively inhibits KCNA5 channels in pulmonary artery smooth muscle cells.
Acute hypoxia causes pulmonary vasoconstriction in part by inhibiting voltage-gated K(+) (Kv) channel activity in pulmonary artery smooth muscle cells (PASMC). The hypoxia-mediated decrease in Kv currents [I(K(V))] is selective to PASMC; hypoxia has little effect on I(K(V)) in mesenteric artery smooth muscle cells (MASMC). Functional Kv channels are homo- and/or heterotetramers of pore-forming alpha-subunits and regulatory beta-subunits. KCNA5 is a Kv channel alpha-subunit that forms functional Kv channels in PASMC and regulates resting membrane potential. We have shown that acute hypoxia selectively inhibits I(K(V)) through KCNA5 channels in PASMC. Overexpression of the human KCNA5 gene increased I(K(V)) and caused membrane hyperpolarization in HEK-293, COS-7, and rat MASMC and PASMC. Acute hypoxia did not affect I(K(V)) in KCNA5-transfected HEK-293 and COS-7 cells. However, overexpression of KCNA5 in PASMC conferred its sensitivity to hypoxia. Reduction of Po(2) from 145 to 35 mmHg reduced I(K(V)) by approximately 40% in rat PASMC transfected with human KCNA5 but had no effect on I(K(V)) in KCNA5-transfected rat MASMC (or HEK and COS cells). These results indicate that KCNA5 is an important Kv channel that regulates resting membrane potential and that acute hypoxia selectively reduces KCNA5 channel activity in PASMC relative to MASMC and other cell types. Because Kv channels (including KCNA5) are ubiquitously expressed in PASMC and MASMC, the observation from this study indicates that a hypoxia-sensitive mechanism essential for inhibiting KCNA5 channel activity is exclusively present in PASMC. The divergent effect of hypoxia on I(K(V)) in PASMC and MASMC also may be due to different expression levels of KCNA5 channels.


The role of recombinant human thyrotropin for diagnostic monitoring of patients with differentiated thyroid cancer.
To describe the evolving role of recombinant human thyrotropin in the diagnostic evaluation of patients treated for differentiated thyroid carcinoma. A systematic review was performed of published English language articles appearing in PubMed using terms "recombinant thyrotropin" and "thyroid cancer". The author selected articles for inclusion based upon potential for clinical impact of the reported findings. The addition of recombinant human thyrotropin to diagnostic testing replaced the requirement for thyroid hormone withdrawal and symptomatic hypothyroidism that had been necessary to generate sufficient endogenous thyrotropin for radioiodine scanning and thyroglobulin testing. The high negative predictive value of stimulated thyroglobulin testing removed the need for serial radioiodine scanning for many patients, but repeated stimulated testing rarely appeared to add significantly. The development of highly sensitive second generation thyroglobulin assays may replace the need for stimulated testing in a subset of patients. Recombinant human thyrotropin-stimulated testing continues to be a valuable component of follow-up testing in the first year after initial treatment of differentiated thyroid cancer.


Association between clinical and surgical variables with postoperative outcomes in patients treated for intestinal obstruction for non-malignant conditions: a cross-sectional study.
Intestinal obstruction is considered a frequent surgical pathology related to previous surgical procedures. Many different factors can lead to different outcomes when surgical management is needed. Therefore, we aim to describe the factors related to morbidity and mortality in surgical management of IO in a single-center experience. Retrospective observational study with a prospective database, in which we described patients who underwent surgical management due to intestinal obstruction between 2004 and 2015. Demographics, perioperative data, surgical outcomes, morbidity, and mortality were described. 366 patients were included. Female were 54.6%. Mean age was 61.26. Laparoscopic approach was done in 21.8% and the conversion rate was 17.2%. Intestinal resection was performed in 37.9% of the cases. Postoperative complications were observed in 18.85%. Reintervention and mortality were 9.5% and 4.1% respectively. Laparoscopic approach shows lesser time of intestinal transit (mean 28.67 vs. mean 41.95 h), and restart of oral intake after surgery (mean 96.06 vs. mean 119.65) compared with open approach. Increased heart rate and intensive care unit length of stay were related with mortality (p 0.01 and 0.000 respectively). For morbidity, laparotomy and need and duration of ICU stay were related with any complication statistically significant (p 0.02, 0.008, 0.000 respectively). Patients with increased heart rate in the emergency room, decreased amount of intravenous fluids, need and higher length of stay in the intensive care unit, and delay in resuming oral intake after surgery appear to have poor outcomes. Laparoscopic approach seems to be a safe and feasible approach for intestinal obstruction in selected patients.


Comparison of stroke volume (SV) and stroke volume respiratory variation (SVV) measured by the axillary artery pulse-contour method and by aortic Doppler echocardiography in patients undergoing aortic surgery.
The goal of the study was to compare stroke volume (SV) and respiratory stroke volume variation (SVV) measured by pulse-contour analysis and aortic Doppler. These were measured by pulse-contour analysis and thermodilution (PiCCO) and by aortic pulsed wave Doppler with transoesophageal echocardiography in patients undergoing abdominal aortic surgery. Simultaneous measurements were done at different times of surgery. All data were recorded on PiCCOwin software and videotape and analysed off-line by a blinded investigator. A total of 114 measurements were achieved in 20 patients. There was a good correlation and small bias between the PiCCO and the echo-Doppler values of the mean SV [r=0.885; bias=0.2 (8) ml], and between the minimum [r=0.842; bias=1 (9) ml] and maximum SV [r=0.840; bias=2 (10) ml] values. There is a fair correlation between pulse-contour analysis and aortic Doppler for beat-by-beat measurement of SV but not for calculation of SV respiratory ventilation.


Snorting benzodiazepines.
Two cases of intranasal benzodiazepine use are presented. The methods of preparation and administration of the powder and accounts of the pharmacological effects of the drugs used are described. The pattern of development and progress of the habit and its associated features are delineated. Snorting benzodiazepines appears to be more common than is currently appreciated, and the clinical complications and implications of this habit are discussed.


The influence of municipal characteristics on the use of informal home care and home care services by the elderly Flemish.
When explaining the use of care, the context of the care gains importance. This article focuses on the influence of the municipality on the lives of the elderly regarding the usage of different forms of care, whereas controlling for the effect of individual characteristics. Two databases on the individual characteristics of elderly Flemish people living at home were combined with a database on municipal characteristics. The effect of municipal characteristics was measured through multi-level logistic regression. A higher mean income per inhabitant and a lower number of inhabitants/100 km(2) have a positive effect on the use of informal home care. The use of home care services is positively influenced by a higher family care index and an increasing relative number of hours of domestic care provided in the municipality. Receiving care from a general practitioner, medical specialist, dentist, emergency department, community nurse, physiotherapist, home aid, day-care centre or hospital with overnight stay is not influenced by the municipality's characteristics. The use of public welfare services, meals-on-wheels programs or hospital outpatients' services, however, are affected by the municipality, but cannot be fully explained by the model. The municipality that an elderly person lives in has an impact on the amount and the types of care an elderly person receives. Persons with similar care needs and similar individual characteristics can receive very different care when they live in different municipalities. This is quite a challenging finding for researchers, as well as for care providers and policy makers.


Ecological Networks and Neighborhood Social Organization.
Drawing on the social disorganization tradition and the social ecological perspective of Jane Jacobs, the authors hypothesize that neighborhoods composed of residents who intersect in space more frequently as a result of routine activities will exhibit higher levels of collective efficacy, intergenerational closure, and social network interaction and exchange. They develop this approach employing the concept of ecological networks-two-mode networks that indirectly link residents through spatial overlap in routine activities. Using data from the Los Angeles Family and Neighborhood Survey, they find evidence that econetwork extensity (the average proportion of households in the neighborhood to which a given household is tied through any location) and intensity (the degree to which household dyads are characterized by ties through multiple locations) are positively related to changes in social organization between 2000-2001 and 2006-2008. These findings demonstrate the relevance of econetwork characteristics-heretofore neglected in research on urban neighborhoods-for consequential dimensions of neighborhood social organization.


Isolation, characterisation and investigation of in vitro antidiabetic and antioxidant activity of phytoconstituents from fruit of Momordica charantia Linn.
The dry powder of MC fruits was extracted by maceration, ultrasonication, liquid-liquid partition and soxhlation. The in vitro antidiabetic and antioxidant assays were used to screen extracts and fractions. Refluxed and liquid partitioned extracts were fractionated using petroleum ether and ethyl acetate and purified with the help of preparative HPLC to give 2 phytoconstituents M1 and M2 respectively. Compound M1 (1) was identified as charantin and Compound M2 (2) was identified as momordicinin using spectral studies. Momordicinin showed potent α-amylase inhibitory activity with IC50 15.86μg/ml which was reported for the first time.


Using the SEIR model to constrain the role of contaminated fomites in spreading an epidemic: An application to COVID-19 in the UK.
The use of the SEIR model of compartmentalized population dynamics with an added fomite term is analysed as a means of statistically quantifying the contribution of contaminated fomites to the spread of a viral epidemic. It is shown that for normally expected lifetimes of a virus on fomites, the dynamics of the populations are nearly indistinguishable from the case without fomites. With additional information, such as the change in social contacts following a lockdown, however, it is shown that, under the assumption that the reproduction number for direct infection is proportional to the number of social contacts, the population dynamics may be used to place meaningful statistical constraints on the role of fomites that are not affected by the lockdown. The case of the Spring 2020 UK lockdown in response to COVID-19 is presented as an illustration. An upper limit is found on the transmission rate by contaminated fomites of fewer than 1 in 30 per day per infectious person (95% CL) when social contact information is taken into account. Applied to postal deliveries and food packaging, the upper limit on the contaminated fomite transmission rate corresponds to a probability below 1 in 70 (95% CL) that a contaminated fomite transmits the infection. The method presented here may be helpful for guiding health policy over the contribution of some fomites to the spread of infection in other epidemics until more complete risk assessments based on mechanistic modelling or epidemiological investigations may be completed.


Granulomatous Response in Intracranial Germinomas: Diagnostic Problems.
Intracranial germinomas are rare and account for <0.5% of primary intracranial tumors. In contrast to the gonadal germinomas, these do not show granulomatous response within the tumor. In rare cases, the granulomatous component may obscure the tumor proper and lead to diagnostic difficulties/dilemmas. We report a case of suprasellar germinoma in a 17-year-old boy which showed granulomatous response. We discuss the differentials to be considered in such a scenario and discuss the utility of squash cytology and immunohistochemistry in these lesions.


Use of inhaled and oral corticosteroids in pregnancy and the risk of malformations or miscarriage.
Corticosteroids are potent anti-inflammatory and immunosuppressive drugs, which sometimes must be given to pregnant women. Corticosteroids have been suspected to be teratogenic for many years; however, there is conflicting evidence regarding the association. Based on a literature review of three databases, this MiniReview provides an overview of inhaled and oral corticosteroid use in pregnancy with specific emphasis on the association between use of corticosteroids during pregnancy and risk of miscarriage and congenital malformations in offspring. The use of corticosteroids among pregnant women ranged from 0.2% to 10% and increased nearly two times in recent years. Taken together, the evidence suggests that the use of corticosteroids in early pregnancy is not associated with an increased risk of congenital malformations overall or oral clefts in offspring; at the same time, published estimates are inconsistent. The use of inhaled corticosteroids was associated with a slightly increased risk of miscarriage, whereas the use of oral corticosteroids was not; however, confounding by indication could not be ruled out.


Sensitivity of commercial scanners to microchips of various frequencies implanted in dogs and cats.
To evaluate the sensitivity of 4 commercially available microchip scanners used to detect or read encrypted and unencrypted 125-, 128-, and 134.2-kHz microchips under field conditions following implantation in dogs and cats at 6 animal shelters. Cross-sectional study. Animals-3,949 dogs and cats at 6 animal shelters. Each shelter was asked to enroll 657 to 660 animals and to implant microchips in 438 to 440 animals (each shelter used a different microchip brand). Animals were then scanned with 3 or 4 commercial scanners to determine whether microchips could be detected. Scanner sensitivity was calculated as the percentage of animals with a microchip in which the microchip was detected. None of the scanners examined had 100% sensitivity for any of the microchip brands. In addition, there were clear differences among scanners in regard to sensitivity. The 3 universal scanners capable of reading or detecting 128- and 134.2-kHz microchips all had sensitivities > or = 94.8% for microchips of these frequencies. Three of the 4 scanners had sensitivities > or = 88.2% for 125-kHz microchips, but sensitivity of one of the universal scanners for microchips of this frequency was lower (66.4% to 75.0%). Results indicated that some currently available universal scanners have high sensitivity to microchips of the frequencies commonly used in the United States, although none of the scanners had 100% sensitivity. To maximize microchip detection, proper scanning technique should be used and animals should be scanned more than once. Microchipping should remain a component of a more comprehensive pet identification program.


Ex vivo detection and characterization of early dental caries by optical coherence tomography and Raman spectroscopy.
Early dental caries detection will facilitate implementation of nonsurgical methods for arresting caries progression and promoting tooth remineralization. We present a method that combines optical coherence tomography (OCT) and Raman spectroscopy to provide morphological information and biochemical specificity for detecting and characterizing incipient carious lesions found in extracted human teeth. OCT imaging of tooth samples demonstrated increased light backscattering intensity at sites of carious lesions as compared to the sound enamel. The observed lesion depth on an OCT image was approximately 290 microm matching those previously documented for incipient caries. Using Raman microspectroscopy and fiber-optic-based Raman spectroscopy to characterize the caries further, spectral changes were observed in PO4 (3-) vibrations arising from hydroxyapatite of mineralized tooth tissue. Examination of various ratios of PO4 (3-) nu2, nu3, nu4 vibrations against the nu1 vibration showed consistent increases in carious lesions compared to sound enamel. The changes were attributed to demineralization-induced alterations of enamel crystallite morphology and/or orientation. OCT imaging is useful for screening carious sites and determining lesion depth, with Raman spectroscopy providing biochemical confirmation of caries. The combination has potential for development into a new fiber-optic diagnostic tool enabling dentists to identify early caries lesions with greater sensitivity and specificity.


[Determination of polymyxin E1 and polymyxin E2 in polymyxin E sulfate using micellar electrokinetic capillary chromatography].
A method of micellar electrokinetic chromatography capillary (MECC) has been established for separating polymyxins E1 and E2 in polymyxin E sulfate and determining the contents of E1 and E2. Several factors including the running voltage, the type of surfactant, concentrations of Brij-35 (polyoxyethylene glycol dodecyl ether), NaCl solution and acetonitrile, pH of phosphate were investigated. Under the optimum conditions (10 kV running voltage, phosphate buffer solution (0.01 mol/L, pH 4.1) containing 30 mmol/L Brij-35, 5% (v/v) acetonitrile, 0.167 mol/L NaCl), E1 and E2 were separated with the resolution of 1.94. The contents of E1 and E2 in polymyxin E sulfate were 67% and 32%, respectively. As an example, the relative standard deviations of the intra-assay and inter-assay of polymyxin E1 on the plate number and peak area were less than 5%. The method is simple, rapid, accurate, and reproducible.


Defensive and Ion Conductive Surface Layer Enables High Rate and Durable O3-type NaNi1/3 Fe1/3 Mn1/3 O2 Sodium-Ion Battery Cathode.
Na-based layered transition metal oxides with an O3-type structure are considered promising cathodes for sodium-ion batteries. However, rapid capacity fading, and poor rate performance caused by serious structural changes and interfacial degradation hamper their use. In this study, a NaPO3 surface modified O3-type layered NaNi1/3 Fe1/3 Mn1/3 O2 cathode is synthesized, with improved high-voltage stability through protecting layer against acid attack, which is achieved by a solid-gas reaction between the cathode particles and gaseous P2 O5 . The NaPO3 nanolayer on the surface effectively stabilizes the crystal structure by inhibiting surface parasitic reactions and increasing the observed average voltage. Superior cyclic stability is exhibited by the surface-modified cathode (80.1% vs 63.6%) after 150 cycles at 1 C in the wide voltage range of 2.0 V-4.2 V (vs Na+ /Na). Moreover, benefiting from the inherent ionic conduction of NaPO3 , the surface-modified cathode presents excellent rate capability (103 mAh g-1 vs 60 mAh g-1 ) at 10 C. The outcome of this study demonstrates a practically relevant approach to develop high rate and durable sodium-ion battery technology.


Hydrogels for 3D bioprinting in tissue engineering and regenerative medicine: Current progress and challenges.
Three-dimensional (3D) bioprinting is a promising and innovative biomanufacturing technology, which can achieve precise position controlling of cells and extracellular matrix components, and further create complex and functional multi-cellular tissues or organs in a 3D environment. Bioink in the form of the cell-loaded hydrogel is most commonly used in bioprinting, and it is vital to the process of bioprinting. The bionic scaffold should possess suitable mechanical strength, biocompatibility, cell proliferation, survival, and other biological characteristics. The disadvantages of natural polymer hydrogel materials include poor mechanical properties as well as low printing performance and shape fidelity. Over the past years, a series of synthetic, modified, and nanocomposite hydrogels have been developed, which can interact through physical interactions, chemical covalent bond crosslinking, and bioconjugation reactions to change the characteristics to satisfy the requirements. In this review, a comprehensive summary is provided on recent research regarding the unique properties of hydrogel bioinks for bioprinting, with optimized methods and technologies highlighted, which have both high-value research significance and potential clinical applications. A critical analysis of the strengths and weaknesses of each hydrogel-based biomaterial ink is presented at the beginning or end of each section, alongside the latest improvement strategies employed by current researchers to address their respective shortcomings. Furthermore, we propose potential repair sites for each hydrogel-based ink based on their distinctive repair features, while reflecting on current research limitations. Finally, we synthesize and analyze expert opinions on the future of these hydrogel-based bioinks in the broader context of tissue engineering and regenerative medicine, offering valuable insights for future investigations.


Induction of long-term remission in advanced hepatocellular carcinoma with percutaneous isolated liver chemoperfusion.
The aim of this study was to report the long-term results of percutaneous isolated liver chemoperfusion with hepatic venous isolation and charcoal hemoperfusion (HVI-CHP) in patients with multiple advanced hepatocellular carcinoma (HCC). The results of conventional chemotherapy including regional and systemic chemotherapy in patients with HCC remain dismal, and long-term survivors after treatment are rare among patients with multiple advanced HCC. In an effort to improve this situation, we previously developed a novel system of percutaneous isolated liver chemoperfusion with HVI-CHP. Doxorubicin (60 to 150 mg/m2) was administered via the hepatic artery, under conditions of extracorporeal drug elimination by HVI-CHP in 28 consecutive patients with advanced HCC (39 total treatments). Hepatic venous isolation and charcoal hemoperfusion was accomplished mainly by the single catheter technique using a newly developed 4-lumen-balloon catheter, which was used to isolate and capture total hepatic venous outflow and, at the same time, to direct the filtered blood to the right atrium. Complete remission was achieved in five patients, of which four received repeated treatments (two or three times). Although 1 of 5 patients with complete remission died of pulmonary metastases at 8 months, the other 4 remain healthy and free of disease at 20, 24, 27, and 42 months after the first treatment. Partial responses were observed in 12 patients. Duration of response in responders (complete and partial) with repeated treatments was significantly longer than that with a single treatment (p = 0.01). The overall survival rate by the Kaplan-Meier method was 39.7% at 5 years. The treatments were well-tolerated, and the primary side effects were mild to moderate chemical hepatitis and reversible myelosuppression. The results suggest that percutaneous isolated liver chemoperfusion with HVI-CHP is an effective palliative treatment in the majority of patients and yields long-term complete remission in some patients with multiple advanced HCC.


Mixed neuroendocrine-non-neuroendocrine neoplasms of the gallbladder: a case report.
Primary neuroendocrine tumors of the gallbladder (GB-NETs) are rare, accounting for 0.5% of all NETs and 2.1% of all gallbladder cancers. Among GB-NETs, mixed neuroendocrine-non-neuroendocrine neoplasms of the gallbladder (GB-MiNENs) are extremely rare. We present the case of a 66-year-old woman who was referred to us for the management of a gallbladder tumor (incidentally found during abdominal ultrasonography indicated for gallbladder stones). The patient had no history of abdominal pain or fever, and the findings on a physical examination were unremarkable. Blood tests showed normal levels of tumor markers. Imaging studies revealed a mass of approximately 10 mm in diameter (with no invasion of the gallbladder bed) located at the fundus of the gallbladder. A gallbladder cancer was suspected. Therefore, an open whole-layer cholecystectomy with regional lymph nodes dissection was performed. The postoperative course was uneventful, and she was discharged on postoperative day 6. Pathological findings showed GB-MiNENs with invasion of the subserosal layer and no lymph node invasion (classified T2aN0M0 pStage IIA according to the Union for International Cancer Control, 8th edition staging system). Analysis of the neuroendocrine markers revealed positive chromogranin A and synaptophysin, and a Ki-67 index above 95%. Fourteen months after the operation, a local recurrence was detected, and she was referred to another hospital for chemotherapy. GB-MiNENs are extremely aggressive tumors despite their tumor size. Optimal therapy should be chosen for each patient.


Surface-initiated atom transfer radical polymerization from halogen-terminated Si(111) (Si-X, X = Cl, Br) surfaces for the preparation of well-defined polymer-Si hybrids.
The halogen-terminated Si(111) (Si-X, X = Cl, Br) surfaces contain effective initiators for surface-initiated atom transfer radical polymerization. Well-defined polymer-Si hybrids, consisting of covalently tethered (Si-C bonded) functional polymer brushes, can be prepared directly from the Si-X surfaces.


Fungal Pigments: Deep into the Rainbow of Colorful Fungi.
With the impact of globalization on research trends, the search for healthier life styles, the increasing public demand for natural, organic, and "clean labelled" products, as well as the growing global market for natural colorants in economically fast-growing countries all over the world, filamentous fungi started to be investigated as readily available sources of chemically diverse pigments and colorants.[...].


State-dependent coupling of hippocampal oscillations.
Oscillations occurring simultaneously in a given area represent a physiological unit of brain states. They allow for temporal segmentation of spikes and support distinct behaviors. To establish how multiple oscillatory components co-vary simultaneously and influence neuronal firing during sleep and wakefulness in mice, we describe a multivariate analytical framework for constructing the state space of hippocampal oscillations. Examining the co-occurrence patterns of oscillations on the state space, across species, uncovered the presence of network constraints and distinct set of cross-frequency interactions during wakefulness compared to sleep. We demonstrated how the state space can be used as a canvas to map the neural firing and found that distinct neurons during navigation were tuned to different sets of simultaneously occurring oscillations during sleep. This multivariate analytical framework provides a window to move beyond classical bivariate pipelines for investigating oscillations and neuronal firing, thereby allowing to factor-in the complexity of oscillation-population interactions.


Sentiment analysis to determine the impact of online messages on smokers' choices to use varenicline.
Social networks are a prominent component of online smoking cessation interventions. This study applied sentiment analysis-a data processing technique that codes textual data for emotional polarity-to examine how exposure to messages about the cessation drug varenicline affects smokers' decision making around its use. Data were from QuitNet, an online social network dedicated to smoking cessation and relapse prevention. Self-reported medication choice at registration and at 30 days was coded among new QuitNet registrants who participated in at least one forum discussion mentioning varenicline between January 31, 2005 and March 9, 2008. Commercially available software was used to code the sentiment of forum messages mentioning varenicline that occurred during this time frame. Logistic regression analyses examined whether forum message exposure predicted medication choice. The sample of 2132 registrants comprised mostly women (78.3%), white participants (83.4%), averaged 41.2 years of age (SD = 10.9), and smoked on average 21.5 (SD = 9.7) cigarettes/day. After adjusting for potential confounders, as exposure to positive varenicline messages outweighed negative messages, the odds of switching to varenicline (odds ratio = 2.05, 95% confidence interval = 1.66 to 2.54) and continuing to use varenicline (odds ratio = 2.46, 95% confidence interval = 1.96 to 3.10) statistically significantly increased. Sentiment analysis is a useful tool for analyzing text-based data to examine their impact on behavior change. Greater exposure to positive sentiment in online conversations about varenicline is associated with a greater likelihood that smokers will choose to use varenicline in a quit attempt.


Daughter Cells and Erythroid Cells Budding from PGCCs and Their Clinicopathological Significances in Colorectal Cancer.
Purpose: We previously reported that polyploid giant cancer cells (PGCCs) induced by cobalt chloride (CoCl2) exhibit cancer stem cell properties. Daughter cells generated by PGCCs possess epithelial mesenchymal transition (EMT) phenotype changes and EMT plays an important role in cancer development and progression. This study investigated the characteristics of PGCCs from LoVo and HCT116 induced by CoCl2 and the clinicopathological significances of PGCCs in colorectal cancer (CRC). Materials and Methods: Western blotting and immunocytochemical staining were used to compare the expression levels of EMT-related proteins between PGCCs with budding daughter cells and the control cells. In addition, tissue samples were collected from 159 patients with CRC for analysis of PGCCs, vasculogenic mimicry (VM), and single stromal PGCCs with budding, as well as immunohistochemical staining for cathepsin B, vimentin, and hemoglobin A. Results: Single PGCCs induced by CoCl2 formed spheroids in vitro. Poorly differentiated CRCs showed the highest numbers of PGCCs and VM, and expression of cathepsin B. There was greater expression of EMT-related proteins in PGCCs with budding daughter cells than in control cells. The expression of vimentin located in PGCC nuclei. Single stomal PGCCs with budding were detected in 27.45% of well differentiated, 50% of moderately differentiated, and 90.20% of poorly differentiated CRC samples. PGCCs can generate erythroid cells that express delta-hemoglobin to form VM. Erythroid cells generated by PGCCs were positive for hemoglobin A immunocytochemical staining. Conclusion: PGCCs from LoVo and HCT116 treated by CoCl2 exhibited cancer stem cell properties. The number of PGCCs and VM were associated with CRC differentiation and daughter cells budded from PGCCs may promote the lymph node metastasis via expression of EMT-related proteins. PGCCs and their newly generated erythroid cells form VM structures.


Diagnostic accuracy of contrast-enhanced ultrasound (CEUS) in monitoring vascular complications in patients after liver transplantation - diagnostic performance compared with histopathological results.
To analyse the diagnostic performance of contrast-enhanced ultrasound (CEUS) in patients with vascular complications and transplant rejection compared to histopathological results. Our study consisted of 45 retrospectively analysed patients that underwent liver transplantations between January 1993 and December 2015 and developed post-transplant vascular complications with transplant rejection. CEUS examinations took place between September 2006 and December 2015. CEUS findings were correlated with histopathological results. CEUS showed a sensitivity of 61.5%, a specificity of 100.0%, a positive predictive value (PPV) of 100.0% and a negative predictive value (NPV) of 86,5% in the detection of vascular complications with post-transplant rejection. 5 examinations were reported as normal whereas the histopathological result showed a transplant rejection (false-negative). CEUS might be a useful additional non-invasive technique for the assessment of vascular complications with post-transplant rejection in patients after liver transplantation.


The Role of (Modified) Lipoproteins in Vascular Function: A Duet Between Monocytes and the Endothelium.
Over the last century, many studies have demonstrated that low-density lipoprotein (LDL) is a key risk factor of cardiovascular diseases (CVD) related to atherosclerosis. Thus, for these CVD patients, LDL lowering agents are commonly used in the clinic to reduce the risk for CVD. LDL, upon modification, will develop distinct inflammatory and proatherogenic potential, leading to impaired endothelial integrity, influx of immune cells and subsequent increased foam cell formation. LDL can also directly affect peripheral monocyte composition, rendering them in a more favorable position to migrate and accumulate in the subendothelial space. It has become apparent that other lipoprotein particles, such as triglyceride- rich lipoproteins or remnants (TRL) and lipoprotein(a) [Lp(a)] may also impact on atherogenic pathways. Evidence is accumulating that Lp(a) can promote peripheral monocyte activation, eventually leading to increased transmigration through the endothelium. Similarly, remnant cholesterol has been identified to play a key role in endothelial dysfunction and monocyte behavior. In this review, we will discuss recent developments in understanding the role of different lipoproteins in the context of inflammation at both the level of the monocyte and the endothelium.


Pan-conserved segment tags identify ultra-conserved sequences across assemblies in the human pangenome.
The human pangenome, a new reference sequence, addresses many limitations of the current GRCh38 reference. The first release is based on 94 high-quality haploid assemblies from individuals with diverse backgrounds. We employed a k-mer indexing strategy for comparative analysis across multiple assemblies, including the pangenome reference, GRCh38, and CHM13, a telomere-to-telomere reference assembly. Our k-mer indexing approach enabled us to identify a valuable collection of universally conserved sequences across all assemblies, referred to as "pan-conserved segment tags" (PSTs). By examining intervals between these segments, we discerned highly conserved genomic segments and those with structurally related polymorphisms. We found 60,764 polymorphic intervals with unique geo-ethnic features in the pangenome reference. In this study, we utilized ultra-conserved sequences (PSTs) to forge a link between human pangenome assemblies and reference genomes. This methodology enables the examination of any sequence of interest within the pangenome, using the reference genome as a comparative framework.


Simulating irradiance and color during lunar eclipses using satellite data.
Irradiance and color during the total lunar eclipses of 2007 and 2008 are simulated using a ray tracing model that includes refraction, scattering by molecules, and observed or climatological distributions of aerosols, ozone, clouds, and topography around the terminator. Central portions of the umbra appear deep red for almost all eclipses due to preferential removal of short wavelengths in the spectrum of sunlight by scattering in the lower troposphere. The fringe of the umbra appears turquoise or blue due to selective removal of wavelengths around 600 nm by the Chappuis absorption bands of ozone in the stratosphere. Asymmetric distributions of clouds and aerosols, particularly for the 2008 eclipse, produce minimum calculated irradiance up to 17 arc min from the umbra center, while high ozone content over the arctic makes the northern edge of the umbra deepest blue.


Investigating the gene expression profiles of rehabilitated Florida manatees (Trichechus manatus latirostris) following red tide exposure.
To investigate a Florida manatee (Trichechus manatus latirostris) mortality event following a red tide bloom in Southwest Florida, an RNA sequencing experiment was conducted. Gene expression changes in white blood cells were assessed in manatees rescued from a red tide affected area (n = 4) and a control group (n = 7) using RNA sequencing. The genes with the largest fold changes were compared between the two groups to identify molecular pathways related to cellular and disease processes. In total, 591 genes (false discovery rate <0.05) were differentially expressed in the red tide group. Of these, 158 were upregulated and 433 were downregulated. This suggests major changes in white blood cell composition following an exposure to red tide. The most highly upregulated gene, Osteoclast associated 2C immunoglobulin-like receptor (OSCAR), was upregulated 12-fold. This gene is involved in initiating the immune response and maintaining a role in adaptive and innate immunity. The most highly downregulated gene, Piccolo presynaptic cytomatrix protein (PCLO), was downregulated by a factor of 977-fold. This gene is associated with cognitive functioning and neurotransmitter release. Downregulation of this gene in other studies was associated with neuronal loss and neuron synapse dysfunction. Among the cellular pathways that were most affected, immune response, including inflammation, wounds and injuries, cell proliferation, and apoptosis were the most predominant. The pathway with the most differentially expressed genes was the immune response pathway with 98 genes involved, many of them downregulated. Assessing the changes in gene expression associated with red tide exposure enhances our understanding of manatee immune response to the red tide toxins and will aid in the development of red tide biomarkers.


A new equation for the accurate calculation of sound speed in all oceans.
A new equation is proposed for the calculation of sound speed in seawater as a function of temperature, salinity, depth, and latitude in all oceans and open seas, including the Baltic and the Black Sea. The proposed equation agrees to better than +/-0.2 m/s with two reference complex equations, each fitting the best available data corresponding to existing waters of different salinities. The only exceptions are isolated hot brine spots that may be found at the bottom of some seas. The equation is of polynomial form, with 14 terms and coefficients of between one and three significant figures. This is a substantial reduction in complexity compared to the more complex equations using pressure that need to be calculated according to depth and location. The equation uses the 1990 universal temperature scale (an elementary transformation is given for data based on the 1968 temperature scale). It is hoped that the equation will be useful to those who need to calculate sound speed in applications of marine acoustics.


A comparative analysis of 3D conformal deep inspiratory-breath hold and free-breathing intensity-modulated radiation therapy for left-sided breast cancer.
Patients undergoing radiation for left-sided breast cancer have increased rates of coronary artery disease. Free-breathing intensity-modulated radiation therapy (FB-IMRT) and 3-dimensional conformal deep inspiratory-breath hold (3D-DIBH) reduce cardiac irradiation. The purpose of this study is to compare the dose to organs at risk in FB-IMRT vs 3D-DIBH for patients with left-sided breast cancer. Ten patients with left-sided breast cancer had 2 computed tomography scans: free breathing and voluntary DIBH. Optimization of the IMRT plan was performed on the free-breathing scan using 6 noncoplanar tangential beams. The 3D-DIBH plan was optimized on the DIBH scan and used standard tangents. Mean volumes of the heart, the left anterior descending coronary artery (LAD), the total lung, and the right breast receiving 5% to 95% (5% increments) of the prescription dose were calculated. Mean volumes of the heart and the LAD were lower (p<0.05) in 3D-DIBH for volumes receiving 5% to 80% of the prescription dose for the heart and 5% for the LAD. Mean dose to the LAD and heart were lower in 3D-DIBH (p≤0.01). Mean volumes of the total lung were lower in FB-IMRT for dose levels 20% to 75% (p<0.05), but mean dose was not different. Mean volumes of the right breast were not different for any dose; however, mean dose was lower for 3D-DIBH (p = 0.04). 3D-DIBH is an alternative approach to FB-IMRT that provides a clinically equivalent treatment for patients with left-sided breast cancer while sparing organs at risk with increased ease of implementation.


Growth and optical properties of strained GaAs-GaxIn 1-x P core-shell nanowires.
We have synthesized GaAs-Ga(x)In(1-x)P (0.34 < x < 0.69) core-shell nanowires by metal-organic vapor phase epitaxy. The nanowire core was grown Au-catalyzed at a low temperature (450 degrees C) where only little growth takes place on the side facets. The shell was added by growth at a higher temperature (600 degrees C), where the kinetic hindrance of the side facet growth is overcome. Photoluminescence measurements on individual nanowires at 5 K showed that the emission efficiency increased by 2 to 3 orders of magnitude compared to uncapped samples. Strain effects on the band gap of lattice mismatched core-shell nanowires were studied and confirmed by calculations based on deformation potential theory.


The varicellovirus-encoded TAP inhibitor UL49.5 regulates the presentation of CTL epitopes by Qa-1b1.
Impairment of MHC class I Ag processing is a commonly observed mechanism that allows viruses and tumors to escape immune destruction by CTL. The peptide transporter TAP that is responsible for the delivery of MHC class I-binding peptides into the endoplasmic reticulum is a pivotal target of viral-immune evasion molecules, and expression of this transporter is frequently lost in advanced cancers. We recently described a novel population of CTL that intriguingly exhibits reactivity against such tumor-immune escape variants and that recognizes self-peptides emerging at the cell surface due to defects in the processing machinery. Investigations of this new type of CTL epitopes are hampered by the lack of an efficient inhibitor for peptide transport in mouse cells. In this article, we demonstrate that the varicellovirus protein UL49.5, in contrast to ICP47 and US6, strongly impairs the activity of the mouse transporter and mediates degradation of mouse TAP1 and TAP2. Inhibition of TAP was witnessed by a strong reduction of surface MHC class I display and a decrease in recognition of conventional tumor-specific CTL. Analysis of CTL reactivity through the nonclassical molecule Qa-1(b) revealed that the presentation of the predominant leader peptide was inhibited. Interestingly, expression of UL49.5 in processing competent tumor cells induced the presentation of the new category of peptides. Our data show that the varicellovirus UL49.5 protein is a universal TAP inhibitor that can be exploited for preclinical studies on CTL-based immune intervention.


Menthol, a bioactive constituent of Mentha, attenuates motion sickness in mice model: Involvement of dopaminergic system.
Motion sickness (MS) occurs due to contradicting vestibular and visual inputs to the brain causing nausea and vomiting. Antidopaminergic drugs being effective in reducing MS create a path for effective therapy against MS by regulating dopamine levels. We aimed to evaluate the role of the striatum and brainstem dopamine and dopamine D2 receptor (DRD2) in MS and the efficacy of menthol (MNT) to modulate dopamine and DRD2 in vitro and in vivo for possible amelioration of MS. Evaluation of efficacy of MNT to inhibit dopamine release from PC12 cells and anti-MS efficacy in BALB/c mice model was performed. Dopamine, DRD2 expression in PC12 cells, mice striatum, and brainstem were detected using HPLC-ECD, RT-PCR, and Western blot analysis, respectively. DRD2 expression increased in calcium ionophore-treated PC12 cells compared with control cells. Pretreatment with 50 μg/ml menthol decreased dopamine and DRD2 expression. Similarly, dopamine and DRD2 levels in mice striatum and brainstem of MS group (rotation induced) increased significantly compared with control group NC (no rotation). Pretreatment with menthol at 50 mg/kg concentration (rotation induced) showed decreased dopamine and DRD2 expression, thus indicating ameliorative effect on MS. Hence, we suggest that increased striatum and brainstem dopamine and DRD2 levels might lead to MS symptoms, and menthol could be used as a potent herbal alternative medicine for MS. PRACTICAL APPLICATIONS: Antidopaminergic drugs being effective in reducing motion sickness (MS) creates a path for effective therapy against MS by regulating dopamine levels. Increased striatum and brainstem dopamine and Dopamine D2 receptor (DRD2) levels might lead to the MS symptoms induced by rotation stimulation in mice model. Menthol showed a prophylactic effect on rotation-induced MS by reducing striatal and brainstem dopamine levels, DRD2 mRNA, and protein expression. Menthol could be used as an herbal alternative to antidopaminergics to minimize the associated adverse effects.


A "How-To" Guide for Designing Judgment Bias Studies to Assess Captive Animal Welfare.
Robust methods to assess nonhuman animal emotion are essential for ensuring good welfare in captivity. Cognitive bias measures such as the judgment bias task have recently emerged as promising tools to assess animal emotion. The simple design and objective response measures make judgment bias tasks suitable for use across species and contexts. In reviewing 64 studies published to date, it emerged that (a) judgment biases have been measured in a number of mammals and birds and an invertebrate; (b) no study has tested judgment bias in any species of fish, amphibian, or reptile; and (c) no study has yet investigated judgment bias in a zoo or aquarium. This article proposes that judgment bias measures are highly suitable for use with these understudied taxa and can provide new insight into welfare in endangered species housed in zoos and aquariums, where poor welfare impacts breeding success and, ultimately, species survival. The article includes a "how-to" guide to designing judgment bias tests with recommendations for working with currently neglected "exotics" including fishes, amphibians, and reptiles.


Endocarditis associated with Escherichia coli in a sea lion (Zalophus californianus).
Endocarditis associated with Escherichia coli was diagnosed in a 2-year-old male California sea lion (Zalophus californianus). The diagnosis was based on light microscopic examination and bacterial isolation from the valvular lesion. This is the first case of bacterial endocarditis reported in a sea lion.


Design and Evaluation of CPR Emergency Equipment for Non-Professionals.
Sudden cardiac death is a sudden and highly fatal condition. Implementing high-quality emergency cardiopulmonary resuscitation (CPR) early on is an effective rescue method for this disease. However, the rescue steps of CPR are complicated and difficult to remember, and the quantitative indicators are difficult to control, which leads to a poor quality of CPR emergency actions outside the hospital setting. Therefore, we have developed CPR emergency equipment with a multisensory feedback function, aiming to guide rescuers in performing CPR through visual, auditory, and tactile interaction. This equipment consists of three components: first aid clothing, an audio-visual integrated terminal, and a vital sign detector. These three components are based on a micro-power WiFi-Mesh network, enabling the long-term wireless transmission of the multisensor data. To evaluate the impact of the multisensory feedback CPR emergency equipment on nonprofessionals, we conducted a controlled experiment involving 32 nonmedical subjects. Each subject was assigned to either the experimental group, which used the equipment, or the control group, which did not. The main evaluation criteria were the chest compression (CC) depth, the CC rate, the precise depth of the CC ratio (5-6 cm), and the precise rate of the CC ratio -(100-120 times/min). The results indicated that the average CC depth in the experimental group was 51.5 ± 1.3 mm, which was significantly better than that of the control group (50.2 ± 2.2 mm, p = 0.012). Moreover, the average CC rate in the experimental group (110.1 ± 6.2 times/min) was significantly higher than that of the control group (100.4 ± 6.6 times/min) (p < 0.001). Compared to the control group (66.37%), the experimental group showed a higher proportion of precise CC depth (82.11%), which is closer to the standard CPR rate of 100%. In addition, the CC ratio of the precise rate was 93.75% in the experimental group, which was significantly better than that of 56.52% in the control group (p = 0.024). Following the experiment, the revised System Availability Scale (SUS) was utilized to evaluate the equipment's usability. The average total SUS score was 78.594, indicating that the equipment's acceptability range was evaluated as 'acceptable', and the overall adjective rating was 'good'. In conclusion, the multisensory feedback CPR emergency equipment significantly enhances the CC performance (CC depth, CC rate, the precise depth of CC ratio, the precise rate of CC ratio) of nonprofessionals during CPR, and the majority of participants perceive the equipment as being easy to use.


[Preparing patients with chronic pulmonary disease for air travel].
Flying is the most important way of travelling in the continually growing international tourism. Number of passengers and those with preexisting diseases, mainly with cardiopulmonary problems, is increasing over years. One of the main tasks of the pre-travel advice is to assess tolerance to hypoxia of the traveler, and specify the necessity, as well as the type and volume of supplementary oxygen therapy. It is indispensable to know the cabin-environment and impact of that on the travelers' health. Travel medicine specialist has to be aware of the examinations which provide information for the appropriate decision on the fit-to-fly condition of the patient. The physician who prepares the patient with chronic obstructive pulmonary disease for repatriation by regular flight and the escorting doctor have to be fully aware of the possibilities, modalities, advantages and contraindications of the on-board oxygen supply and therapy. In this review, the authors give a summary of literature data, outline the tools of in-flight oxygen therapy as well as discuss possibilities for the preflight assessment of patients' condition including blood gas parameters required for safe air travel, as recommended in international medical literature. The preparation process for repatriation of patients with chronic obstructive pulmonary disease is also discussed.


Chlorpromazine bioavailability from a topical gel formulation in volunteers.
Symptom management medications are often compounded into topical gel formulations providing an alternative route of administration for hospice and palliative care patients. Though commonly used, transdermal absorption and bioavailability studies of these gel products are lacking. Chlorpromazine was studied because it is FDA approved for treatment of nausea and vomiting and is used off-label for treatment of agitation and delirium. The objective of this study is to determine the transdermal absorption of chlorpromazine PLO gel in healthy adults. Twenty-five milligrams of chlorpromazine in PLO gel was applied to 10 subjects' wrists and 100 mg was applied to 1 subject's wrist. Blood draws were completed preapplication and 1, 2, and 4 hours postapplication. This single-center unblinded study recruited healthy adults between 18 and 70 years of age. Participants were not pregnant, did not have an allergy to any component of the study medication, and were not taking a phenothiazine medication. Chlorpromazine was undetected in any of the 11 subjects' blood samples. There is an assumption of equivalent medication absorption in healthy patients and palliative care or hospice patients. Rapid relief of symptoms at end of life is essential. Chlorpromazine in PLO gel may not be an effective treatment option since blood levels were undetectable at 1, 2, and 4 hours after topical application.


Multicenter trials need to use the same assay for hepatitis C virus viral load determination.
This study, involving 20 laboratories and using currently available assays for hepatitis C virus RNA quantification, demonstrated that differences in viral load values are due not to interlaboratory variations but rather to the nature of the assay itself. This underlines the importance of using the same assay in multicenter studies or when monitoring antiviral therapy.


[Occlusion of central venous port catheters after simultaneous 24 h infusions of 5-FU and calcium-folinic acid in patients with gastrointestinal cancer].
Folinic acid-modulated 5-FU regimens are standard elements in several chemotherapy combinations like FOLFIRI, FOLFOX or AIO-regimen in the palliative treatment of patients with gastrointestinal cancer. When the simultaneous mixed infusion of 5-FU and calcium-folinic acid (Leucovorin) was authorized by the BfArM in 2002, we introduced this application regimen in the treatment of our cancer patients. 19 patients (AIO-regimen [5], FOLFIRI [12] and FOLFOX [2]) received a simultaneously mixed infusion of calcium-folinic acid and 5-FU over 24 hours with a total of 110 applications. 5-FU doses varied between 2000 and 2600 mg/m2, calcium-folinic acid was given with 500 mg/m2, infusion rate was 10 ml/hour using a 24 h pump. Central venous catheters employed included single Barth-Port in 18 cases, 1 patient had a Viggon-Port. In 3 out of the 19 patients catheter occlusion was noticed after 8-10 weekly applications of the mixed infusion. Heparine and subsequently urokinase were not successful in reversing the obstruction. All three catheters had to be explanted. Catheter tips in all cases showed a yellow cristalline precipitation. The crystallographic analysis exhibited calcium carbonate (CaCO3) in its polymorphic form (calcite). Thus, we confirmed calcite formation causing catheter occlusion as a frequent complication during a continuous 24 h-infusion of mixed high dose 5-FU and calcium-folinic acid. This reaction could not be avoided by increasing infusion volume and the application flow rate. As a result of our findings, recommending using calcium-folinic acid mixed with 5-FU has been withdrawn in the meantime.


Western European responses to physician oversupply. Lessons for the United States.
The supply and specialty distribution of physicians in Belgium, West Germany, the Netherlands, and the United Kingdom were compared with those in the United States. The numbers of physicians per 10,000 population in 1980 was 24 (Belgium), 22.9 (West Germany), 19.1 (United States), 19.0 (the Netherlands), and 16.2 (United Kingdom). Projections for 1990 were 34 (Belgium), 32.6 (West Germany), 24.3 (United States), and 17.1 (United Kingdom). The United States and the United Kingdom produce about half as many physicians per population but have a much higher proportion (26%) of foreign physicians. The United States has a much higher ratio of specialists to generalists. Official recognition of physician oversupply exists in Belgium, which is restricting specialty training, and the Netherlands, which is reducing both medical school intake and specialty training, but not yet in West Germany. The European experience suggests that the United States' most pressing health manpower problem is an oversupply of specialists.


Transgenic Canola Oil Improved Blood Omega-3 Profiles: A Randomized, Placebo-Controlled Trial in Healthy Adults.
Long-chain omega-3 polyunsaturated fatty acids (LC-ω3 PUFA), including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), play key roles in physiological functions and disease prevention. The nutrient gap in meeting LC-ω3 intake recommendations in the U.S. and globally can be addressed by alternative sources of LC-ω3. This randomized, placebo-controlled, seamless phase I/II study evaluated the pharmacokinetics, safety, and efficacy of a transgenic LC-ω3-rich canola oil in healthy adults. Participants (n = 33/group) were randomized to receive low-, mid-, or high-dose of the LC-ω3-rich oil (providing 285, 570, or 1,140 mg LC-ω3 PUFA, respectively) or placebo (corn oil). After one dose, plasma ω3 (primary outcome) levels were assessed over a 72 h pharmacokinetic period. Whole blood and red blood cells (RBC) ω3 and serum cardiovascular biomarkers were assessed during a 16-week continuation period with daily supplementation. Compared to low-dose and placebo, high-dose group showed greater DHA AUC0-72h and C max . A linear response was observed for DHA and EPA AUC0-72h . Compared to placebo, high- and mid-dose groups showed increased whole blood DHA, EPA, α-linolenic acids (ALA) (high-dose only), omega-3 score, and omega-3 index after 4 weeks, and increased DHA and EPA in RBC after 16 weeks (P < 0.05). No changes in cardiovascular biomarkers were seen. Overall, this LC-ω3-rich oil demonstrated good DHA bioavailability and significantly improved short and long-term blood LC-ω3 profiles. Sixteen weeks of daily supplementation of the LC-ω3-rich oil was safe and well-tolerated.


[Antiinflammatory treatment in patients with chronic back pain].
Non-steroidal anti-inflammatory drugs (NSAIDs) are part of the treatment of patients with chronic nonspecific back pain (CBP). An analysis of the reasons for the absence of NSAIDs administration or cancellation of previously iniciated NSAIDs in patients with CBP was the goal of this study. We analyzed the peculiarities of treatment of CBP in 250 patients at baseline and after 1 and 2 years. The features of drug therapy, the reasons for therapy cancellation were evaluated. 52 (20.8%) of patients with CBP were not treated with NSAIDs, 38 (15.2%) recieved NSAIDs in 4 and > days per week, 44 (17.6%) - 3 and < days a week, 62 (24.8%) took NSAID in 7-14 day 2-5 times per year, 54 (21.6%) - in on-demand mode. Absence of NSAIDs administration in CBP was associated with older age, the presence of comorbidites, with non-alcoholic fatty liver disease and obesity. The cancelletion of previously initiated NSAID was equally associated with the resolution of pain and with the failure to respond to therapy, with the presence of obesity and with the intake of nonselective NSAIDs. Continuation of the initiated effective anti-inflammatory therapy was associated with the use of coxibs, complex treatment with the use of neirobion, with the presence of normal body weight, and with the achievement of a decrease in the severity of the pain syndrome even in the absence of its complete resolution. Increased adherence to treatment with NSAIDs in CBP patients can be achieved by increasing of its effectiveness through the use of NSAIDs (especially coxibs) with B group vitamins (B1, B6, B12), by normalizing of BMI and effectively controlling liver function.


Medulloblastoma in a patient successfully treated for immature teratoma of the ovary.
We report a case of medulloblastoma as a secondary malignancy in a patient treated for immature teratoma of the ovary (ITO). ITO is a rare but curable tumor of the ovary using combination chemotherapy. There is a great deal of interest in the long-term effects of chemotherapy in these patients. Once regarded as fatal not many series of patients with ITO have been reported with the long follow up as in the present case. This case may start a debate on the susceptibility of central nervous system tumors following chemotherapy in patients with ITO.


Biomorphometric analysis of ilio-sacro-iliacal corridors for an intra-osseous implant to fix posterior pelvic ring fractures.
It is hypothesized that ilio-sacro-iliacal corridors for a new envisioned pelvic ring implant (trans-sacral nail with two iliacal bolts = ISI-nail: ilio-sacro-iliacal nail) exists on the level of S1- or S2-vertebra in each patient. The corridors of 84 healthy human pelves (42x ♂; 42x ♀, 18-85 years) were measured in high resolution CT scans using the Merlin Diagnostic Workcenter Software. Trans-sacral corridors (≥ 9 mm diameter) on the level of S1 and S2 were found in 62% and 54% of pelves with a mean length [mm ± SD] of 164 ± 12.9 and 142 ± 10.2. Corresponding iliac corridors were present in all specimens in caudally tilted axial planes of 37.8 ± 0.67° and 53.7 ± 0.94° in relation to the operating table plane and divergent angulations of 69.0 ± 0.49° and 70.1 ± 0.32° in relation to the sagittal midline plane. Sacral dysmorphism, with compensatory larger S2 corridors were prevalent in 24% of pelves; ilio-sacro-iliacal osseous corridors for the envisioned implant were found in 88% of pelves on the level of S1 or S2. In the remaining 12% with too narrow corridors for any trans-sacral implant (screws, bars, ISI nail) alternative fixation methods have to be considered. Expected advantages of the envisioned ISI nail compared to available fixation devices are discussed.


[Treatment of a septic patient with acquired haemophilia].
Acquired haemophilia is a rare bleeding diathesis caused by auto-immune depletion of factor VIII. It is characterised by spontaneous haemorrhagic syndrome, which can be fatal sometimes. A 71 year-old man presents in a dysimmunitary context (rheumatoid arthritis complicates by an acquired haemophilia) a septicemia with a methicillin resistant staphylococcus aureus. At the time of the hospitalization, the patient is febrile (39 degrees C). The activated partial thromboplastin time is very much increased, the level of factor VIII is lowered by 7% and the title of the inhibitor to factor VIII amounts to 140 Bethesda unities. An haematoma of the right root thigh is also noted. In that case, the concomitant presence of septicemia makes difficult the use of immunosuppressive therapy usually recommended to decrease auto-antibody's level. For the management of the septicemia, an adapted antibiotherapy (vancomycin then teicoplanin) is organized to J1. To control haemorrhagic risk, immunoglobulins are prescribed from d12 to d16, without immediate results. Then prednisone is introduced. We observe a very fast decrease of the anticoagulant circulating title with a neat improvement of the clinical state, allowing so to realize a draining puncture of the psoas. This invasive investigation required the use of prothrombinic complex concentrates ((Feiba) in the dose of 80 UI/kg two to three times a day). Biopsy does not show infection source. The infection delayed the prescription of immunosuppressive therapy and the surgery. Use of corticoids, following 5 days of intravenous polyvalent immunoglobulin, was the good choice. After 7 weeks of hospitalization the patient has recovered a normal haemostasis results, and a good general state.


Home-visit nurses' attitudes for providing effective assistance to clients with schizophrenia.
There were two objectives of this study. The first was to identify the attitudes of home-visit nurses towards clients with schizophrenia that lead to the provisions of effective care and positive client outcomes for clients with schizophrenia. The second was to develop a framework to understand how nurses acquire nursing attitudes that lead to such provisions. Seven expert home-visit nurses who had successfully prevented rehospitalization of clients with schizophrenia for more than 2 years were interviewed. In the semistructured interviews, the nurses described their experiences in assisting one or two clients. Data were analyzed qualitatively. The central theme was having equal footing with the client. An effective nursing attitude was acquired through recognizing one's own preconceptions of clients with schizophrenia through two steps: encountering unexpected client behaviours and becoming aware of one's problematic care. For these clients, it was essential that the nurses reflect on their preconceptions towards clients with schizophrenia and alter these preconceptions by working with the clients and believing in their innate ability to live in the community. The findings suggest that the field of mental health home-visit nursing might benefit from adding these educational components in order to cultivate effective nursing attitudes for assisting clients with schizophrenia.


Selective Depletion of Adult GFAP-Expressing Tanycytes Leads to Hypogonadotropic Hypogonadism in Males.
In adult mammals, neural stem cells are localized in three neurogenic regions, the subventricular zone of the lateral ventricle (SVZ), the subgranular zone of the dentate gyrus of the hippocampus (SGZ) and the hypothalamus. In the SVZ and the SGZ, neural stem/progenitor cells (NSPCs) express the glial fibrillary acidic protein (GFAP) and selective depletion of these NSPCs drastically decreases cell proliferation in vitro and in vivo. In the hypothalamus, GFAP is expressed by α-tanycytes, which are specialized radial glia-like cells in the wall of the third ventricle also recognized as NSPCs. To explore the role of these hypothalamic GFAP-positive tanycytes, we used transgenic mice expressing herpes simplex virus thymidine kinase (HSV-Tk) under the control of the mouse Gfap promoter and a 4-week intracerebroventricular infusion of the antiviral agent ganciclovir (GCV) which kills dividing cells expressing Tk. While GCV significantly reduced the number and growth of hypothalamus-derived neurospheres from adult transgenic mice in vitro, it causes hypogonadotropic hypogonadism in vivo. The selective death of dividing tanycytes expressing GFAP indeed results in a marked decrease in testosterone levels and testicular weight, as well as vacuolization of the seminiferous tubules and loss of spermatogenesis. Additionally, GCV-treated GFAP-Tk mice show impaired sexual behavior, but no alteration in food intake or body weight. Our results also show that the selective depletion of GFAP-expressing tanycytes leads to a sharp decrease in the number of gonadotropin-releasing hormone (GnRH)-immunoreactive neurons and a blunted LH secretion. Overall, our data show that GFAP-expressing tanycytes play a central role in the regulation of male reproductive function.


Functional variation of SHP-2 promoter is associated with preterm birth and delayed myelination and motor development in preterm infants.
Src homology 2 domain-containing protein tyrosine phosphatase 2 (SHP-2) is a cytoplasmic tyrosine phosphatase that is highly expressed in hematopoietic cells and in the CNS and exerts opposite effects on signal transduction by exerting a neuroprotective or proapoptotic effect. Several mutations of SHP-2 have been found in children with myeloproliferative disorders or malignant leukemia, and some of these can affect brain development. In the present study, we aimed to identify and functionally characterize genetic variations in SHP-2 in 72 preterm and 58 full-term infants and to evaluate the effect of the variations on neurodevelopment in preterm infants. Twelve genetic variations were identified. Among them, two variations in the SHP-2 promoter, g.-317C > T and g.-273G > A, were found to significantly increase promoter activity, and the frequency of g.-273G > A was higher in preterm infants than in full-term infants. Two transcription factors, NF-κB and GABPα, were found to be involved in the transcriptional regulation of SHP-2 by the two above-mentioned variations. In particular, we found that g.-273G > A was significantly associated with delayed myelination and poor motor development in preterm infants. Our results suggest that a functional promoter variation in SHP-2 is associated with spontaneous preterm birth itself as well as white matter myelination and neurodevelopment.


Mucosal squamous cell carcinoma of the esophagus: a clinicopathologic study of 30 cases.
A clinicopathologic study was carried out on 30 patients with mucosal esophageal cancer (MEC). The depth of cancer invasion was subdivided histologically into three categories: m1 = carcinoma in situ (intraepithelial carcinoma) or carcinoma with questionable invasion beyond the basal membrane; m2 = cancer invasion confined to the lamina propria, and m3 = cancer reaching to or infiltrating into the muscularis mucosae. Lymph node metastases and lymphatic invasion were found only in the tumors reaching or infiltrating the muscularis mucosae (m3). The maximum histologic vertical extent of the tumors was more than 1 mm in 4 of 5 patients with lymph node metastasis or lymphatic invasion. None of the patients died of recurrent esophageal disease, and 3 of the 6 patients who had a second primary tumor died of this other malignancy. It is critical to distinguish between m1, m2 and m3 tumors to plan a treatment strategy, including an endoscopic mucosal resection.


Murine coronavirus delays expression of a subset of interferon-stimulated genes.
The importance of the type I interferon (IFN-I) system in limiting coronavirus replication and dissemination has been unequivocally demonstrated by rapid lethality following infection of mice lacking the alpha/beta IFN (IFN-alpha/beta) receptor with mouse hepatitis virus (MHV), a murine coronavirus. Interestingly, MHV has a cell-type-dependent ability to resist the antiviral effects of IFN-alpha/beta. In primary bone-marrow-derived macrophages and mouse embryonic fibroblasts, MHV replication was significantly reduced by the IFN-alpha/beta-induced antiviral state, whereas IFN treatment of cell lines (L2 and 293T) has only minor effects on replication (K. M. Rose and S. R. Weiss, Viruses 1:689-712, 2009). Replication of other RNA viruses, including Theiler's murine encephalitis virus (TMEV), vesicular stomatitis virus (VSV), Sindbis virus, Newcastle disease virus (NDV), and Sendai virus (SeV), was significantly inhibited in L2 cells treated with IFN-alpha/beta, and MHV had the ability to rescue only SeV replication. We present evidence that MHV infection can delay interferon-stimulated gene (ISG) induction mediated by both SeV and IFN-beta but only when MHV infection precedes SeV or IFN-beta exposure. Curiously, we observed no block in the well-defined IFN-beta signaling pathway that leads to STAT1-STAT2 phosphorylation and translocation to the nucleus in cultures infected with MHV. This observation suggests that MHV must inhibit an alternative IFN-induced pathway that is essential for early induction of ISGs. The ability of MHV to delay SeV-mediated ISG production may partially involve limiting the ability of IFN regulatory factor 3 (IRF-3) to function as a transcription factor. Transcription from an IRF-3-responsive promoter was partially inhibited by MHV; however, IRF-3 was transported to the nucleus and bound DNA in MHV-infected cells superinfected with SeV.


Leptospirosis Infection Misdiagnosed as COVID-19: A Rare Case Report.
Leptospirosis is an acute, febrile, systemic, and zoonotic infectious disease characterized by widespread vasculitis caused by Leptospira interrogans from the leptospira family. It can be in the form of asymptomatic infection; it can also progress with severe symptomatic forms characterized by multiorgan involvement such as aseptic meningitis as well as liver and kidney failure. Leptospirosis is transmitted to humans through water, soil, and food contaminated with the urine of infected mice or other mammals. COVID-19 is a newly detected coronavirus that causes pneumonia. The disease has led to a pandemic all over the world. In this case report, we aimed to draw attention to leptospirosis infection in the presence of a case who was followed up with the differential diagnosis of COVID-19 and diagnosed with leptospirosis during the COVID-19 pandemic. Leptospirosis is one of the diagnoses that should be kept in mind in especially developing countries in patients presenting with findings that may be confused with COVID-19 during the pandemic period.


3-Hydroxyterphenyllin, a natural fungal metabolite, induces apoptosis and S phase arrest in human ovarian carcinoma cells.
In the present study, we evaluated 3-Hydroxyter-phenyllin (3-HT) as a potential anticancer agent using the human ovarian cancer cells A2780/CP70 and OVCAR-3, and normal human epithelial ovarian cells IOSE-364 as an in vitro model. 3-HT suppressed proliferation and caused cytotoxicity against A2780/CP70 and OVCAR-3 cells, while it exhibited lower cytotoxicity in IOSE-364 cells. Subsequently, we found that 3-HT induced S phase arrest and apoptosis in a dose-independent manner. Further investigation revealed that S phase arrest was related with DNA damage which mediated the ATM/p53/Chk2 pathway. Downregulation of cyclin D1, cyclin A2, cyclin E1, CDK2, CDK4 and Cdc25C, and the upregulation of Cdc25A and cyclin B1 led to the accumulation of cells in S phase. The apoptotic effect was confirmed by Hoechst 33342 staining, depolarization of mitochondrial membrane potential and activation of cleaved caspase-3 and PARP1. Additional results revealed both intrinsic and extrinsic apoptotic pathways were involved. The intrinsic apoptotic pathway was activated through decreasing the protein levels of Bcl2, Bcl-xL and procaspase-9 and increasing the protein level of Puma. The induction of DR5 and DR4 indicated that the extrinsic apoptotic pathway was also activated. Induction of ROS and activation of ERK were observed in ovarian cancer cells. We therefore concluded that 3-HT possessed anti-proliferative effect on A2780/CP70 and OVCAR-3 cells, induced S phase arrest and caused apoptosis. Taken together, we propose that 3-HT shows promise as a therapeutic candidate for treating ovarian cancer.


Research Progress of Perfluoroalkyl Substances in Edible Oil-A Review.
Perfluoroalkyl substances (PFASs) have been widely used in different types of consumer and industrial applications such as surfactants, household cleaning products, textiles, carpets, cosmetics, firefighting foams, and food packaging because of their good stability and special physicochemical properties of hydrophobicity, oleophobicity, high temperature resistance, etc. Meanwhile, PFASs are considered an emerging organic pollutant due to their persistence and potential toxicity to human health. PFASs occur in edible oil, an important component of the global diet, mainly in three ways: raw material contamination, process contamination, and migration from oil contact materials. Thus, the occurrence of PFAS in edible oils has drawn more and more attention in recent years. In this work, the pertinent literature of the last two decades from the Web of Science database was researched. This review systematically addressed the potential sources, the contamination levels, and the progress of the determination of PFASs in edible oil. It aims to provide a relatively whole profile of PFASs in edible oil, render assistance to minimise human exposure to PFASs, and standardise the detection methods of perfluoroalkyl substances in edible oil.


Effects of low-dose corticosteroids on the bone mineral density of patients with rheumatoid arthritis: a meta-analysis.
: The effects of long-term high-dose corticosteroids on bone mineral density (BMD) are clear, but the effects of low-dose corticosteroids in patients with rheumatoid arthritis (RA) remain controversial. The aim of this study was to assess the effects of low-dose corticosteroids on BMD in patients with RA. : The authors surveyed randomized controlled studies that examined the effects of low-dose corticosteroids on BMD in patients with RA using MEDLINE and the Cochrane Controlled Trials Register and by performing manual searches. Data were collected on BMD (end-of-period or change-from-baseline) after longest recorded treatment durations. Meta-analysis was performed using a random effects model; outcomes are presented as standardized mean differences (SMDs). : Seven studies were included in this meta-analysis, which included 7 studies on lumbar BMD meta-analysis and 6 studies on femur BMD meta-analysis. Corticosteroids resulted in a moderate worsening in lumbar BMD compared with controls (SMD = -0.483; 95% confidence interval [CI], -0.815 to -0.151, P = 0.004), whereas the femoral BMD differences were not siginificant (SMD = -0.224; 95% CI, -0.663 to 0.215, P = 0.318). Subgroup analysis of BMD data performed on a change-from-baseline basis showed that corticosteroids had a clear effect on both lumbar and femoral BMDs (SMD = -0.354; 95% CI, -0.620 to -0.088, P = 0.009; SMD = -0.488; 95% CI, -0.911 to -0.065, P = 0.024, respectively). : This meta-analysis shows BMD loss after low-dose corticosteroid treatment in patients with RA. These findings have practical implications for the long-term management of patients with RA on low-dose corticosteroids.


Comparison of speech perception skills in young and old listeners.
A companion paper (Yanz. 1984, Ear Hear. 5, 64-71) has described an approach to the quantification of speech perception using measures derived from the theory of signal detection (TSD). The present experiment uses this approach to compare speech perception in young and old listeners in terms of the traditional word recognition score (%C), the ability to assess the accuracy of one's own identifications [P(A)], and the decision criterion used in that assessment (B). Monosyllables were presented in a background of broadband noise at two signal-to-noise ratios (S/N), 0 dB and 5 dB. Subjects recorded their identification of each test item and then rated their confidence in that identification on a six-point scale. Results indicated that in this particular task, neither %C nor B differed between the two age groups, but both quantities varied with S/N. P(A) was the same for the two groups at S/N = 0 dB but differed at S/N = 5 dB. The young group showed significant improvement in P(A) from the 0-dB to the 5-dB S/N condition, while old subjects showed no change. These results suggest that young subjects are more able than older subjects to adapt to and take advantage of an improvement in the acoustic environment.


Small things matter: Implications of APP intracellular domain AICD nuclear signaling in the progression and pathogenesis of Alzheimer's disease.
Alzheimer's disease (AD) is the most common neurodegenerative disease with tens of millions of people affected worldwide. The pathogenesis is still poorly understood and various therapeutical approaches targeting the amyloid β (Aβ) peptide, a product of the amyloidogenic cleavage of the amyloid precursor protein (APP), failed. Moreover, a couple of studies critically questioned the relevance of Aβ in the pathogenesis of AD. Thus, new ideas need to be studied and one highly interesting hypothesis is the APP mediated signal transduction to the nucleus. As a consequence nuclear -potentially toxic- structures emerge, which were recently found to a high extent in human AD tissue and thus, may contribute to neurodegeneration. Relevant for the signaling machinery are modifications at the very C-terminal end of the precursor protein, the APP intracellular domain (AICD). In this review we update the knowledge on mechanisms on AICD referring to our 2008 article: The amyloid precursor protein intracellular domain (AICD) as modulator of gene expression, apoptosis, and cytoskeletal dynamics-Relevance for Alzheimer's disease (T. Muller, et al., 2008). We summarize how AICD is generated and degraded, we describe its intramolecular motifs, translational modifications, and how those as well as APP dimerization influence AICD generation and function. Moreover, we resume the AICD interactome and elucidate AICDs involvement in nuclear signaling, transcriptional regulation, cell death, DNA repair and cell cycle re-entry and we give insights in its physiological function. Results are summarized in the comprehensive poster "The world of AICD".


Kinetic changes of melatonin release in rat pineal perifusions at different circadian stages. Effects of corticosteroids.
The kinetic characteristics of melatonin release were documented in perifused pineal glands removed from rats sacrificed at six circadian stages (light/dark = 12:12): three during the light phase, i.e. 3, 7 and 11 hours after light onset (HALO), and three during the dark phase, i.e. 15, 19 and 23 HALO. Whatever the circadian stage, the melatonin release decreased during the first 3-4 h and then remained fairly constant and roughly similar up to 8 h of perifusion. However, the kinetics of the release in the first 3 h differed in perifusions of pineal glands removed during the light (progressive decline during 3 h) as compared to perifusions of pineal glands removed during the dark (sharp decline during the first hour and then a progressive decline until reaching a constant level after 3 h). As the effects of steroid administration on melatonin secretion are a matter of controversy, we also studied the direct effects and their circadian stage dependence, if any, of corticosterone, deoxycorticosterone and dexamethasone on melatonin secretion by pineal glands removed 7 HALO (about the middle of the light phase) and 19 HALO (about the middle of the dark phase). High concentrations of corticosterone (0.8 x 10(-3) mol/l) and dexamethasone (0.4 x 10(-3) mol/l) resulted in a significant (p < 0.001) inhibitory effect on melatonin production (about a 50% and a 30% decrease, respectively) whatever the circadian stage, whereas lower concentrations (10(-4)-10(-5) mol/l) of both steroids did not affect melatonin production.(ABSTRACT TRUNCATED AT 250 WORDS)


Effect of Cell Sheet Manipulation Techniques on the Expression of Collagen Type II and Stress Fiber Formation in Human Chondrocyte Sheets.
Cell sheet technology is applied to human articular chondrocytes to construct a tissue-like structure as an alternative treatment for cartilage defect. The effect of a gelatin manipulator, as a cell sheet transfer system, on the quality of the chondrocyte sheets was investigated. The changes of important chondrogenic markers and stress fibers, resulting from the cell sheet manipulation, were also studied. The chondrocyte cell sheets were constructed with patient-derived chondrocytes using a temperature-responsive polymer and a gelatin manipulator as a transfer carrier. The properties of the cell sheets, including sizes, expression levels of collagen type II and I, and the localization of the stress fibers, were assessed and compared with those of the cell sheets harvested without the gelatin manipulator. Using the gelatin manipulator, the original size of the chondrocyte cell sheets was retained with abundant stress fibers, but with a decrease in the expression of collagen type II. Without the gelatin manipulator, although the cell shrinkage occurred, the cell sheet with suppressed stress fiber formation showed significantly higher levels of collagen type II. These results support our observations that stress fiber formation in chondrocyte cell sheets affected the production of chondrogenic markers. These densely packed tissue-like structures possessed a good chondrogenic activity, indicating their potential for use in autologous chondrocyte implantation to treat cartilage defects.


Inhibition of SPHK1 suppresses phorbol 12-myristate 13-acetate-induced metastatic phenotype in colorectal cancer HT-29 cells.
Expression of sphingosine kinase 1 (SPHK1) plays a role in colorectal cancer progression. This study aimed to demonstrate the mechanism of human colorectal cancer cell metastatic phenotype through SPHK1 knockdown. Human colorectal cancer HT-29 cells were stimulated by phorbol 12-myristate 13-acetate (PMA) with or without SPHK1 siRNA transfection. Tumor cell phenotypic changes were analyzed by using invasion, motility, cell viability, and apoptosis assays. Gene expressions were assessed using Western blot. PMA induced a metastatic phenotype in colorectal cancer cells, as indicated by cell viability, migration and invasion capacity, and ERK1/2 phosphorylation, whereas SPHK1 siRNA transfection suppressed the metastatic phenotype of tumor cells and antagonized PMA's effects. SPHK1 knockdown also inhibited secretion of MMP-2 and MMP-9 into the tumor cell conditioned medium. Suppression of SPHK1 expression suppresses the PMA-induced metastatic phenotype via ERK1/2 phosphorylation in human colorectal cancer cells.