Synthesis and Biological Evaluation of Novel Dehydroabietic Acid-Oxazolidinone Hybrids for Antitumor Properties.
Novel representatives of the important group of biologically-active, dehydroabietic acid-bearing oxazolidinone moiety were synthesized to explore more efficacious and less toxic antitumor agents. Structures of all the newly target molecules were confirmed by IR, ¹H-NMR, 13C-NMR, and HR-MS. The inhibitory activities of these compounds against different human cancer cell lines (MGC-803, CNE-2, SK-OV-3, NCI-H460) and human normal liver cell line LO2 were evaluated and compared with the commercial anticancer drug cisplatin, using standard MTT (methyl thiazolytetrazolium) assay in vitro. The pharmacological screening results revealed that most of the hybrids showed significantly improved antiproliferative activities over dehydroabietic acid and that some displayed better inhibitory activities compared to cisplatin. In particular, compound 4j exhibited promising cytotoxicity with IC50 values ranging from 3.82 to 17.76 µM against all the test cell lines and displayed very weak cytotoxicity (IC50 > 100 µM) on normal cells, showing good selectivity between normal and malignant cells. Furthermore, the action mechanism of the representative compound 4j was preliminarily investigated by Annexin-V/PI dual staining, Hoechst 33258 staining, which indicated that the compound can induce cell apoptosis in MGC-803 cells in a dose-dependent manner and arrest the cell cycle in G1 phase. Therefore, 4j may be further exploited as a novel pharmacophore model for the development of anticancer agents.


Protocol for efficient regulation of in vitro morphogenesis in einkorn (Triticum monococcum L.), a recalcitrant diploid wheat species.
Einkorn (Triticum monococcum L.) is A-genome diploid wheat that has a potential to become a useful model for understanding the biology and genomics in Triticeae. Unfortunately, the application of modern technologies such as genetic engineering, RNAi-based gene silencing and genome editing is not available for einkorn as there is no efficient in vitro tissue culture and plant regeneration system. In the present study an efficient and simple protocol for plant regeneration via direct or indirect somatic embryogenesis and organogenesis has been developed. Various auxins used as sole inductors in einkorn displayed low effect for morphogenesis (0-8%) and plant regeneration (1-2 shoots per explant). The addition of Daminozide, the inhibitor of biosynthesis of gibberellins, together with auxin significantly improved the formation of morphogenic structures, especially when Dicamba (51.4%) and Picloram (56.6%) were used for combination; furthermore, the simultaneous addition of cytokinin into induction medium significantly promoted in vitro performance. Among the tested cytokinins, the urea-type substances, such as TDZ and CPPU were more effective than the adenine type ones, BA and Zeatin, for the regulation of morphogenesis; especially, TDZ was more effective than CPPU for shoot formation (11.73 vs. 7.04 per regenerating callus). The highest morphogenic response of 90.2% with the production of more than 10 shoots per initial explant was observed when 3.0 mg/L Dicamba, 50.0 mg/L Daminozide and 0.25 mg/L TDZ were combined together. Along with the identification of appropriate induction medium, the optimal developmental stage for einkorn was found as partially transparent immature embryo in size of around 1.0 mm. Although in the present study the critical balance between plant growth regulators was established for einkorn only, we assume that further the proposed strategy could be successfully applied to other recalcitrant cereal species and genotypes.


Travel medicine physician adherence to guidelines for the emergency self treatment of malaria.
Few studies have examined emergency self treatment (EST) antimalarial prescribing patterns. 110 physician-members of the Travel Medicine Society of Ireland and British Global and Travel Health Association participated in this study. There was a trend towards the prescription of EST for travel to remote low-risk malaria areas; for long-term residents living in low-risk areas; and for frequent travellers to low-risk areas. This study provides insights into the use of EST in travellers' malaria.


Thoracic intramedullary epidermoid with paraplegia for 12 years.
A man presented with progressive motor and sensory loss in both lower limbs for 12 years with fecal and urinary incontinence MRI of dorsal spine showed an intramedullary mass in the dorsal cord at D5-D6 level which had a pearly white appearance on exploration. Complete excision was performed leading to good recovery in sensation, movements and sphincter control. Epidermoids should be considered in differential diagnosis of intramedullary tumours. Their removal leads to complete recovery.


Knowledge, attitudes and perceptions regarding human papillomavirus among university students in Hail, Saudi Arabia.
Human papillomavirus (HPV) is a well-known cause of cervical cancer. The prevalence of HPV, insufficient preventive services, inadequate treatment access, socioeconomic conditions, certain cultural causes and values and opinions regarding cervical cancer have been established as factors contributing to the occurrence of cervical cancer in various parts of the world. To determine university students' knowledge, attitudes and perceptions regarding HPV and its vaccine. The present cross-sectional study included students enrolled at the University of Hail, Saudi Arabia. Data were collected from January to May 2020 using a previously validated 26-item questionnaire. A total of 386 participants responded to the survey; the response rate was 80%. The majority of the respondents (63%) were male and 332 (86%) respondents were single among the overall study population. Most respondents were aged 21-25 years (75.6%), followed by 26-30 years (12.7%). In total, 130 (33.7%) respondents reported that they had heard of HPV before, while 174 (45.1%) reported that HPV infections are rare in Saudi Arabia. Furthermore, 102 (26.4%) respondents thought that HPV causes genital warts, while almost 29.5% believed that HPV infection is a sexually transmitted disease. Nearly 76.2% of the respondents did not believe that HPV infection can occur without symptoms. Moreover, 53.4% of the respondents stated that they did not know the health problems associated with HPV infection, while 148 (38.8%) stated that cervical cancer is a health problem associated with HPV infection. When asked about their understanding of the HPV vaccine, nearly 267 (62.2%) respondents believed that there is no vaccine for HPV, while 239 (61.9%) believed that the vaccine does not minimise the risk of cervical cancer. In addition, the respondents reported that they would be far more likely to get an HPV vaccine if recommended by their doctors [relative importance index (RII) = 0.745], followed by their friends (RII = 0.675). The present findings provide a clear understanding of university students' knowledge, perceptions and attitudes regarding HPV; this information can be used to raise awareness by developing an effective educational strategy. However, further research with a larger sample size is recommended; such efforts would also aid in the development of educational services for various age ranges.


[Myocardial inflammation and injury induced by coronary microembolization in rats: role of ERK1/2 signaling pathway].
To determine the role of extracellular signal-regulated kinases1/2 (ERK1/2) signaling pathway in regulating myocardial inflammation and cardiac function in a rat model of coronary microembolization (CME). The Sprague-Dawley rats were randomly divided into three groups: sham-operated group (n = 15), coronary microembolization group (n = 15) and PD98059 group (n = 15). CME model was established by injection of 42 microm microspheres 0.1 ml (3 x 10(4)/ml, 3000)into left ventricle while occluding the ascending aorta. At 30 minutes pre-operation, rats of PD98059 group were injected with PD98059 IV, a specific ERK1/2 inhibitor. Western blot and immunochemical analysis were used to determine the activation and distribution of ERK1/2. Echocardiography was employed to evaluate cardiac functions. The hematoxylin-eosin staining was used to assay myocardial inflammation. Expression of TNF-alpha and MIF mRNA was determined by RT-PCR analysis and activity of NF-kappaB assessed by electrophoretic mobility shift assay. In comparison with sham-operated group, CME increased phosphorylation of ERK1/2 (0.92 +/- 0.10 vs 0.61 +/- 0.04), local myocardial inflammatory cells (455 +/- 16 vs 47 +/- 7), expression of TNF-alpha mRNA (0.94 +/- 0.04 vs 0.60 +/- 0.09) and MIF mRNA(1.30 +/- 0.44 vs 0.63 +/- 0.25) and activity of NF-kappaB (541 +/- 25 vs 311 +/- 65) in myocardium(all P < 0.05). All of these dramatically induced cardiac dysfunction [LVEF (73 +/- 3)% vs (83 +/- 4)%, P < 0.05]. To compare with CME group, treatment of specific ERK1/2 inhibitor PD98059 blocked the activation of ERK1/2 (0.48 +/- 0.11 vs 0.92 +/- 0.10, P < 0.05), decreased inflammatory cells (401 +/- 12 vs 455 +/- 16, P < 0.05), decreased expression of TNF-alpha mRNA (0.42 +/- 0.06 vs 0.94 +/- 0.04, P < 0.05) and suppressed activity of NF-kappaB (105 +/- 14 vs 541 +/- 25, P < 0.05). Most importantly, PD98059 treatment ameliorated cardiac functions dramatically [LVEF (76 +/- 4)% vs (73 +/- 3)%, P < 0.05]. However there was no significant change in the expression of MIF mRNA (1.17 +/- 0.37 vs 1.30 +/- 0.44, P > 0.05). The present study demonstrates a novel role of ERK1/2 signaling pathway in promoting myocardial inflammation in CME. And ERK1/2 may be a novel drug target for CME therapy.


Ground and excited states of NH4: Electron propagator and quantum defect analysis.
Vertical excitation energies of the Rydberg radical NH4 are inferred from ab initio electron propagator calculations on the electron affinities of NH4+. The adiabatic ionization energy of NH4 is evaluated with coupled-cluster calculations. These predictions provide optimal parameters for the molecular-adapted quantum defect orbital method, which is used to determine Einstein emission coefficients and radiative lifetimes. Comparisons with spectroscopic data and previous calculations are discussed.


Retrospective evaluation of 4 methods for outcome prediction in overt disseminated intravascular coagulation in dogs (2009-2014): 804 cases.
The clinical diagnosis of disseminated intravascular coagulation (DIC) in dogs is challenging. It was hypothesized that dogs with laboratory abnormalities consistent with overt DIC have increased mortality and hence survival could be used to evaluate the performance of DIC scoring systems. Four DIC scoring systems were compared in clinically ill dogs: The International Society of Thrombosis and Haemostasis (ISTH) score; a previously published veterinary DIC score; a system using in-house reference intervals (RIs) for coagulation assays; and the published veterinary DIC score modified by use of in-house RI values. Retrospective cohort study. University teaching hospital. Eight hundred four client-owned dogs with underlying disorders associated with DIC. None. Medical records were reviewed to identify dogs for which a coagulation panel consisting of coagulation times, D-dimer concentration, antithrombin activity, fibrinogen concentration, and platelet count had been analyzed. Four methods for overt DIC scoring were then applied, and the ability of these scores to predict mortality was evaluated. Use of institution RIs for diagnosis of overt DIC provided the most accurate prognostic assessment. A score based on abnormalities in 3 of 6 parameters to identify overt DIC was 72.7% sensitive and 80.9% specific for mortality and was accurate in 78.4% of cases. The mortality rate of dogs diagnosed with overt DIC via this method was 62.5%, compared to 12.9% in the dogs not in overt DIC, a relative risk of nonsurvival of 4.84 (95% confidence interval 3.80-6.16). In dogs at-risk for DIC, an in-house RI scoring system accurately predicted mortality. With further prospective validation, this system holds promise as a diagnostic tool for consistent characterization of overt DIC in clinical studies and clinical practice.


The role of n-3 PUFA-derived fatty acid derivatives and their oxygenated metabolites in the modulation of inflammation.
Notwithstanding the ongoing debate on their full potential in health and disease, there is general consensus that n-3 PUFAs play important physiological roles. Increasing dietary n-3 PUFA intake results in increased DHA and EPA content in cell membranes as well as an increase in n-3 derived oxylipin and -endocannabinoid concentrations, like fatty acid amides and glycerol-esters. These shifts are believed to (partly) explain the pharmacological and anti-inflammatory effects of n-3 PUFAs. Recent studies discovered that n-3 PUFA-derived endocannabinoids can be further metabolized by the oxidative enzymes CYP-450, LOX and COX, similar to the n-6 derived endocannabinoids. Interestingly, these oxidized n-3 PUFA derived endocannabinoids of eicosapentaenoyl ethanolamide (EPEA) and docosahexaenoyl ethanolamide (DHEA) have higher anti-inflammatory and anti-proliferative potential than their precursors. In this review, an overview of recently discovered n-3 PUFA derived endocannabinoids and their metabolites is provided. In addition, the use of chemical probes will be presented as a promising technique to study the n-3 PUFA and n-3 PUFA metabolism within the field of lipid biochemistry.


Privacy and security issues in teleradiology.
Teleradiology is now well established within healthcare in the USA, but ethico-legal concepts surrounding this innovation remain unclear. New legislation, the Health Insurance Portability and Accountability Act, as well as ethical guidelines and common law demonstrate the importance being placed on security of electronic data and the protection of patients' personal data. Radiologists need to be aware of the security, privacy, and confidentiality issues which relate to teleradiology, so that they can safeguard not only their own interests but also the best interests of their patients.


Perceptions of critical and emergency department nurses regarding changes in their professional role.
Objective Preliminary investigation of the way Greek critical and emergency department nurses conceptualize changes in their professional role. Method A qualitative focus-group methodology was applied. Following purposeful sampling and informed consent of participants. Results Participated eight individuals. The need for enhancement of nurses' participation in decision-making in order for an actual change in their professional role to be achieved was the central theme of participants' narratives. Perceived advancements in professional role performance regarded: evidence-based practice; technology; education, knowledge; clinical skills; research; heightened nurse-physician collaboration. Perceived reasons why these advancements failed to enhance nurses' professional role were lack of meritocracy; competitive relationships; lack of support among nurses; insufficient managerial support; budget limitations. Conclusion Despite advancements in clinical practice, participants did not deem that their professional role was enhanced significantly, as participation in decision-making and control over practice remain limited. Interventions targeted to enhance nurses' participation in clinical decision-making, and overall professional autonomy are recommended.


[Management and treatment of headache in the pain clinic].
Nerve block therapy is one of the non-pharmacological methods in headache treatment. Most pain clinics in Japan use nerve block therapy to treat pain together with pharmacological methods. Sensory nerve blocks such as the trigger point block, occipital nerve block, trigeminal nerve block, C-2, 3 spinal nerve block, etc., are effective for headache pain. One of the characteristic treatments of headache in the pain clinic in Japan is the stellate ganglion block(SGB). Although it has not been fully clarified why SGB is effective in treating headache, stabilization of the abnormal sympathetic nerve function, suppression of inflammation of vascular wall etc., are thought to be related to the effectiveness of SGB. Nerve block therapy is effective for the treatment of headache patients and offers us an important therapeutic option for treatment of headache pain.


High-Frequency Ultrasound: Description of Sacral Tissue Characteristics in Healthy Adults.
The purpose of this study was to describe selected sacral tissue characteristics in a convenience sample of healthy volunteer subjects. Descriptive. Fifty healthy volunteers in a clinical learning center in a school of nursing. Sacral scans were obtained using a 20-MHz ultrasound scanning system in 3 positions: prone and 60° and 90° side-lying from the back. The images were analyzed by software in the ultrasound program using quantitative parameters of dermal thickness and density (dermal median intensity and derived number of low-echogenic pixels to total pixels [LEP:TP] ratio). In general, average values were as follows: dermal thickness between 2.32 and 2.65 mm; median pixel intensity between 102 and 112; and the LEP:TP ratio between 0.39 and 0.56. There were significant differences in sacral tissue characteristics between measures of thickness and dermal density (median intensity and LEP:TP ratio) by subject side-lying position (60° and 90°) versus prone position, with all P values less than .0001. Overall, the ranges were consistent across measures of thickness and dermal density except for systematic differences between side-lying and prone positions. When comparing thickness, median intensity, or LEP:TP ratio, it is important to report subject position. To best recognize tissue inflammation indicative of pressure injuries before surface changes are seen, it is useful to understand healthy high-frequency ultrasound sacral tissue characteristics. It is anticipated that quantitative assessment of dermal thickness, density, and LEP:TP ratio could help identify individuals with incipient pressure injury.


Helically Coiled Graphene Nanoribbons.
Graphene is a zero-gap, semiconducting 2D material that exhibits outstanding charge-transport properties. One way to open a band gap and make graphene useful as a semiconducting material is to confine the electron delocalization in one dimension through the preparation of graphene nanoribbons (GNR). Although several methods have been reported so far, solution-phase, bottom-up synthesis is the most promising in terms of structural precision and large-scale production. Herein, we report the synthesis of a well-defined, helically coiled GNR from a polychlorinated poly(m-phenylene) through a regioselective photochemical cyclodehydrochlorination (CDHC) reaction. The structure of the helical GNR was confirmed by 1 H NMR, FT-IR, XPS, TEM, and Raman spectroscopy. This Riemann surface-like GNR has a band gap of 2.15 eV and is highly emissive in the visible region, both in solution and the solid state.


Comparing laboratory surveillance with the notifiable diseases surveillance system in South Africa.
The aim of this study was to compare laboratory surveillance with the notifiable diseases surveillance system (NDSS) in South Africa. Data on three tracer notifiable diseases - measles, meningococcal meningitis, and typhoid - were compared to assess data quality, stability, representativeness, sensitivity and positive predictive value (PPV), using the Wilcoxon and Chi-square tests, at the 5% significance level. For all three diseases, fewer cases were notified than confirmed in the laboratory. Completeness for the laboratory system was higher for measles (63% vs. 47%, p<0.001) and meningococcal meningitis (63% vs. 57%, p<0.001), but not for typhoid (60% vs. 63%, p=0.082). Stability was higher for the laboratory (all 100%) compared to notified measles (24%, p<0.001), meningococcal meningitis (74%, p<0.001), and typhoid (36%, p<0.001). Representativeness was also higher for the laboratory (all 100%) than for notified measles (67%, p=0.058), meningococcal meningitis (56%, p=0.023), and typhoid (44%, p=0.009). The sensitivity of the NDSS was 50%, 98%, and 93%, and the PPV was 20%, 57%, and 81% for measles, meningococcal meningitis, and typhoid, respectively. Compared to laboratory surveillance, the NDSS performed poorly on most system attributes. Revitalization of the NDSS in South Africa is recommended to address the completeness, stability, and representativeness of the system.


Comparison of quantitative measurements of four manufacturer's metal artifact reduction techniques for CT imaging with a self-made acrylic phantom.
Metal artifact reduction (MAR) techniques can improve metal artifacts of computed tomography (CT) images. This work focused on conducting a quantitative analysis to compare the effectiveness of four commercial MAR techniques on three types of metal implants (hip implant, spinal implant, and dental filling) with a self-made acrylic phantom. A cylindrical phantom was made from acrylic with a groove in the middle, and then three types of metal implants were placed in the groove. The phantom was scanned by four CT scanners and four commercialized MAR techniques were used to analyze the images. The techniques used were single-energy metal artifact reduction (SEMAR, Canon), smart metal artifact reduction software (Smart-MAR, GE), iterative metal artifact reduction (IMAR, Siemens), and metal artifact reduction for orthopedic implants (OMAR, Philips). Quantitative analysis methods included objective and subjective analysis. The expected value of SEMAR, Smart-MAR, IMAR, and OMAR were 36.6, 37.8, 5.0, and 2.3, respectively. SEMAR and Smart-MAR achieved optimal results. This study successfully evaluated the effects of four commercial MAR techniques on three types of metal implants in a phantom. All MAR techniques effectively reduced metal artifacts, but the effect was not significant with dental fillings due to high-density material.


[T-lymphocyte precursors--the target cells of thymocyte growth factor].
The cortisol-resistant PNA+SC- --1+Thy--1+-thymocytes are the target cells for the thymocyte growth factor (THGF), which is produced by the lines of transformed precursors of T-lymphocytes (PTL). These cells have the same properties and markers as the intrathymic PTL. The bone marrow cells do not proliferate in response to THGF but acquire that ability after the influence of thymic hormones, which induce the maturation of PTL. Thus, THGF is the autocrine growth factor of intrathymic PTL.


Ameliorative effects of 3,4-oxo-isopropylidene-shikimic acid on experimental colitis and their mechanisms in rats.
The aim of the present study was to investigate the therapeutic effect and mechanism of 3,4-oxo-isopropylidene-shikimic acid (ISA) on 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced colitis in rats. (50, 100, 200 mg/kg) was administered for 14 days, 1 day after the induction of colitis by TNBS. The colonic injury and inflammation were assessed by macroscopic damage scores and myeloperoxidase (MPO) activity. Malondialdehyde (MDA) and nitric oxide (NO) levels, and superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities in plasma were measured with biochemical methods. Prostaglandin E2 (PGE2) level in colon was determined by radioimmunoassay. Expressions of inducible nitric oxide synthase (iNOS), cyclo-oxygenase-2 (COX-2), inhibitor kappa B-alpha (IκBα) and nuclear factor kappa B (NF-κB) p65 proteins in the colonic tissue were detected with immunohistochemistry. Enhanced colonic mucosal injury, inflammatory response and oxidative stress were observed in the animals clystered with TNBS, which was manifested as the significant increase in colon mucosal damage index, MPO activity, levels of MDA, NO and PGE2, as well as the expressions of iNOS, COX-2 and NF-κB p65 proteins in the colonic mucosa, and the significant decrease in expressions of IκBα proteins in the colonic mucosa. However, these parameters were found to be significantly ameliorated in rats treated with ISA at given doses, especially at 100 mg/kg and 200 mg/kg. Administration of ISA may have significant therapeutic effects on experimental colitis in rats, probably due to its mechanism of antioxidation, its inhibition of arachidonic acid metabolism and its modulation of the IκBα/NF-κB p65 expression.


Sex, body size, and boldness shape the seasonal foraging habitat selection in southern elephant seals.
Selecting foraging habitat is a fundamental behavior in the life of organisms as it directly links resource acquisition to fitness. Differences in habitat selection among individuals may arise from several intrinsic and extrinsic factors, and yet, their interaction has been given little attention in the study of wild populations. We combine sex, body size, and boldness to explain individual differences in the seasonal foraging habitat selection of southern elephant seals (Mirounga leonina) from the Kerguelen Archipelago. We hypothesize that habitat selection is linked to the trade-off between resource acquisition and risk, and that individuals differ in their position along this trade-off because of differences in reproductive strategies, life stages, and metabolic requirements. Before the post-molt foraging trip, we used a novel object approach test to quantify the boldness of 28 subadult and adult females and 42 subadult males and equipped them with data loggers to track their movements at sea. Subadult males selected neritic and oceanic habitats, whereas females mostly selected less productive oceanic habitats. Both sexes showed a seasonal shift from Antarctic habitats in the south in the summer to the free of ice subantarctic and subtropical habitats in the north in the winter. Males avoided oceanic habitats and selected more productive neritic and Antarctic habitats with body size mostly in the winter. Bolder males selected northern warmer waters in winter, while shyer ones selected the Kerguelen plateau and southern colder oceanic waters. Bolder females selected the Kerguelen plateau in the summer when prey profitability is assumed to be the highest. This study not only provides new insights into the spatiotemporal foraging ecology of elephant seals in relation to personality but also emphasizes the relevance of combining several intrinsic and extrinsic factors in understanding among-individual variation in space use essential in wildlife management and conservation.


Calibration errors of Goldmann tonometers in a tertiary eye care centre.
To evaluate the calibration errors of all Goldmann applanation tonometers used clinically in the Vancouver General Hospital/University of British Columbia (VGH/UBC) Eye Care Centre. All Goldmann tonometers used for patient care in the VGH/UBC Eye Care Centre were individually assessed for calibration errors. The tonometers were checked according to the Haag-Streit method using a standard calibration weight bar at 3 pressure levels (0, 20, 60 mm Hg). Calibration errors were classified into 3 categories: +/-0.5 mm Hg, +/-1.0 mm Hg, or +/-1.5 mm Hg or more. Ophthalmologists using tonometers with calibration errors > +/-1.0 mm Hg were notified, with the suggestion that the tonometers be returned to the manufacturer for recalibration. A total of 25 tonometers were evaluated. At the 20 mm Hg level, 17 (68%) fell within the manufacturer's recommended calibration range of +/-0.5 mm Hg, and 2 (8%) had errors of +/-1.0 mm Hg, resulting in 19 tonometers (76%) with errors of +/-1.0 mm Hg. Six tonometers (24%) were identified as having calibration errors greater than +/-1.0 mm Hg. Calibration error of +/-1.0 mm Hg or less is clinically acceptable. Seventy-six percent of the Goldmann applanation tonometers in the Eye Care Centre were in the acceptable calibration range. As the number of acceptably calibrated tonometers was high, despite the infrequency of recent calibration, we feel that monthly evaluation of Goldmann tonometers is suitable.


Establishment of relative and absolute configurations of phaeosphaeride A: total synthesis of ent-phaeosphaeride A.
The relative and absolute configurations of phaeosphaeride A have been established via the first total synthesis of ent-phaeosphaeride A. The three contiguous stereogenic centers were installed by Sharpless asymmetric dihydroxylation and a stereoselective intramolecular vinyl anion aldol reaction. This synthesis has altered the originally proposed structure of natural phaeosphaeride A.


Case studies on remediating memory deficits in brain-damaged individuals.
Two case reports illustrate the application of mnemonic techniques for the remediation of memory problems common to brain-damaged patients. A clinical paradigm for such work that includes general and specific assessment; laboratory evaluation of intervention strategies, and finally in-vitro application is described.


Antimicrobial activities and susceptibility testing considerations of ampicillin, cephalothin, cefaclor, and cefuroxime against invasive isolates of Haemophilus influenzae.
The activities of ampicillin, cefaclor, cephalothin, and cefuroxime against invasive clinical isolates of Haemophilus infleunzae were studied to determine the correlation between resistance and beta-lactamase production. Approaches to in vitro susceptibility testing of cephalosporins in the clinical laboratory were also assessed. Three hundred and eight isolates of H. influenzae were tested for ampicillin susceptibility, and those which required for inhibition greater than or equal to 1.0 micrograms/ml of ampicillin were tested for beta-lactamase production with a chromogenic cephalosporin. Twenty-two percent of isolates produced beta-lactamase and 85% were serotype b. All isolates considered resistant (MIC greater than or equal to 2.0 micrograms/ml) to ampicillin produced beta-lactamase. A single beta-lactamase-producing isolate was identified, but was inhibited by 1.0 microgram/ml of ampicillin, and a zone diameter of 20 mm was produced by disk diffusion testing. One hundred and ninety-seven isolates were tested for susceptibility to cefaclor, cefuroxime, and cephalothin. Chloramphenicol susceptibility testing by disk diffusion was also performed on these isolates. General agreement and interchangeable results were found among these three cephalosporins by both agar dilution and disk diffusion methods. We conclude that ampicillin-resistant H. influenzae not producing beta-lactamase is rare among these isolates of H. influenzae responsible for invasive disease. Susceptibility testing results of cephalothin, cefaclor, or cefuroxime appear to be interchangeable, although results of cephalothin testing would tend to underestimate the activities of cefaclor or cefuroxime.


Characteristic oscillatory brain networks for predicting patients with chronic migraine.
To determine specific resting-state network patterns underlying alterations in chronic migraine, we employed oscillatory connectivity and machine learning techniques to distinguish patients with chronic migraine from healthy controls and patients with other pain disorders. This cross-sectional study included 350 participants (70 healthy controls, 100 patients with chronic migraine, 40 patients with chronic migraine with comorbid fibromyalgia, 35 patients with fibromyalgia, 30 patients with chronic tension-type headache, and 75 patients with episodic migraine). We collected resting-state magnetoencephalographic data for analysis. Source-based oscillatory connectivity within each network, including the pain-related network, default mode network, sensorimotor network, visual network, and insula to default mode network, was examined to determine intrinsic connectivity across a frequency range of 1-40 Hz. Features were extracted to establish and validate classification models constructed using machine learning algorithms. The findings indicated that oscillatory connectivity revealed brain network abnormalities in patients with chronic migraine compared with healthy controls, and that oscillatory connectivity exhibited distinct patterns between various pain disorders. After the incorporation of network features, the best classification model demonstrated excellent performance in distinguishing patients with chronic migraine from healthy controls, achieving high accuracy on both training and testing datasets (accuracy > 92.6% and area under the curve > 0.93). Moreover, in validation tests, classification models exhibited high accuracy in discriminating patients with chronic migraine from all other groups of patients (accuracy > 75.7% and area under the curve > 0.8). In conclusion, oscillatory synchrony within the pain-related network and default mode network corresponded to altered neurophysiological processes in patients with chronic migraine. Thus, these networks can serve as pivotal signatures in the model for identifying patients with chronic migraine, providing reliable and generalisable results. This approach may facilitate the objective and individualised diagnosis of migraine.


DEVELOPMENTS IN VALUE FRAMEWORKS TO INFORM THE ALLOCATION OF HEALTHCARE RESOURCES.
In recent years, there has been a surge in the development of frameworks to assess the value of different types of health technologies to inform healthcare resource allocation. The reasons for, and the potential of, these value frameworks were discussed during the 2017 Health Technology Assessment International (HTAi) Policy Forum Meeting. This study reflects the discussion, drawing on presentations from invited experts and Policy Forum members, as well as a background paper. The reasons given for a proliferation of value frameworks included: rising healthcare costs; more complex health technology; perceived disconnect between price and value in some cases; changes in societal values; the need for inclusion of additional considerations, such as ethical issues; and greater empowerment of clinicians and patients in defining and using value frameworks. Many Policy Forum participants recommended learning from existing frameworks. Furthermore, there was a desire to agree on the core components of value frameworks, defining the additional value elements as necessary and considering how they might be measured and used in practice. Furthermore, adherence to the principles of transparency, predictability, broad stakeholder involvement, and accountability were widely supported, along with being forward looking, explicit, and consistent across decisions. Value frameworks continue to evolve with significant implications for global incentives for innovation and access to health technologies. There is a role for the HTA community to address some of the key areas discussed during the meeting, such as defining the core components for assessing the value of a health technology.


Intracortical facilitation within the migraine motor cortex depends on the stimulation intensity. A paired-pulse TMS study.
Connectivity within the primary motor cortex can be measured using the paired-pulse transcranial magnetic stimulation (TMS) paradigm. This evaluates the effect of a first conditioning stimulus on the motor evoked potential (MEP) elicited by a second test stimulus when different interstimulus intervals are used. Aim of the present study was to provide, in patients suffering from migraine without aura (MwoA), additional information on intracortical facilitation (ICF), short intracortical inhibition (SICI), and long intracortical inhibition (LICI), using different intensities of the test stimulus (TS). We enrolled 24 patients with episodic MwoA and 24 age- and sex-matched healthy volunteers. Both patients and controls were randomly assigned to two different experimental groups: the first group underwent evaluation of ICF, while in the second group we assessed SICI and LICI. All these measures were assessed by using three different suprathreshold intensities of the TS (110%, 130% and 150% of the resting motor threshold, RMT). Interstimulus intervals (ISIs) of 10 ms were used for testing ICF, while SICI and LICI were carried out by using 2 ms and 100 ms ISIs respectively. All migraine patients underwent the experimental protocol while in the interictal pain-free state. A main finding of the study was that an increased ICF could be seen in migraineurs as compared to the healthy subjects only by using a 110% intensity of the TS. Instead, no significant differences were observed between patients and controls as regards both measures of intracortical inhibition. We show that hyperresponsivity of the glutamatergic intracortical circuits can be detected in the migraine motor cortex only by applying a low suprathreshold intensity of stimulation. Our results strengthen the notion that, to be reliable, the assessment of cortical excitability in migraine should always include evaluation of the cortical response to different stimulation intensities.


Preattentive memory-based comparison of sound intensity.
Changes in the intensity of repeated, ignored sounds elicit the mismatch negativity (MMN) brain response which reflects preattentive detection of the change. It is generally assumed that the MMN in response to intensity changes reflects a memory-based comparison mechanism rather than being due to differential states of refractoriness of intensity-specific cortical neurons. In the present study, an experimental protocol consisting of 4 oddball blocks and 1 control block was used in order to separate memory-comparison-related effects from refractoriness-related ones. This design allowed an assessment of intensity MMN using physically identical stimuli with equal probability of occurrence in separate blocks, while avoiding contamination by refractoriness. Results were consistent with an MMN in response to intensity change that reflects genuine memory-based comparison.


Independent action of serine/threonine protein phosphatase in ovarian cancer plasma membrane and cytosol during gonadotropin-releasing hormone stimulation.
Reversible serine/threonine protein phosphorylation catalyzed by kinases and phosphatases 2A (PP2A) plays a crucial role in cellular growth and differentiation. We attempted to determine the subcellular location of PP2A in ovarian cancer cells and its regulation by gonadotropin-releasing hormone (GnRH), which is known to have anti-proliferative actions on ovarian cancers. Surgically removed ovarian cancers were screened for GnRH receptor expression prior to subcellular fractionations. PP2A activity was assessed by measuring the dephosphorylation of phosphopeptide highly selective for the PP2A in cytosol and membranes fractionated on a continuous sucrose density gradient. To assess GnRH effects, cloned cell lines were pretreated with or without a GnRH agonist. There were three peaks of PP2A activity, corresponding by marker enzyme analysis to the cytoplasm, plasma membrane and endoplasmic reticulum fractions. The kinetic analysis showed a different activity in cytosol and membrane; Km values for substrate of 185 microM and Vmax of 555 pmol/mg protein/30 min for cytosol, and 28 microM and 83 pmol/mg protein/30 min for plasma membrane, respectively. PP2A-specific inhibitor okadaic acid inhibited the cytosolic and membrane-associated activity by 50% when added at 2 nM and 50 nM (p<0.001). A 50% inhibitory effect of NaF was obtained at 0.5-1 mM for cytosol and 5 mM for membranes (p<0.001). In Caov-3 cells exposed GnRH, PP2A activity of plasma membrane increased by 1.3-fold (p<0.001) but that of cytosol was not affected. PP2A activity in the plasma membrane of ovarian cancer cells might be distinct from that present in the cytosol. The plasma membrane PP2A may be responsible for a portion of an increased ser/thr protein phosphorylation-dephosphorylation turnover that occurs during cell exposure to GnRH.


[A child with substantially itchy bumps on the back].
A 2-year-old boy showed itchy papules and wheals, which were diagnosed as papular urticaria. Papular urticaria are a hypersensitivity reaction after insect bites. The condition can relapse even without the presence of insects or new bites. Topical steroids or antihistamines diminish the symptoms in some cases.


Transition to Virtual Learning During the Coronavirus Disease-2019 Crisis in Iran: Opportunity Or Challenge?
COVID-19 is a respiratory disease that can spread from one person to person. This virus is a novel coronavirus that was first identified during an investigation into an outbreak in Wuhan, China. Iran's novel coronavirus cases reached 17,361 on 17 March, while death toll reached approximately 1,135. Its first death was officially announced on 20 February 2020 in Qom. The 2019 coronavirus pandemic has affected educational systems around the world, Also in Iran, and led to the closure of face to face courses in schools and universities. Therefore, virtual education can be seen as a turning point in education of these days in Iran.


Alopecia areata in infants and newborns.
Alopecia areata is a common cause of nonscarring hair loss in children and adults. In newborns and very young infants, however, it is thought to be extremely rare. In this article we describe five cases of alopecia areata in patients less than 6 months of age and briefly discuss the pertinent differential diagnosis of infants and newborns with both patchy and complete hair loss. We propose that alopecia areata may be more common in this age group than the literature suggests.


Prevalence of alpha-subunit hypersecretion in patients with pituitary tumors: clinically nonfunctioning and somatotroph adenomas.
Hypersecretion of the pituitary glycoprotein hormone alpha-subunit has been reported in pituitary adenomas, particularly in clinically nonfunctioning tumors and somatotroph adenomas. However, the prevalence of such hypersecretion has not been precisely defined. Using both a new highly sensitive and specific monoclonal antibody assay and a polyclonal antibody assay, serum levels of free alpha-subunit were compared in 63 unselected patients with these tumors, 19 patients with acromegaly, and 95 normal controls. In all patients the monoclonal assay detected a significantly greater number of subjects with elevated alpha-subunit levels than did the polyclonal assay (21 vs. 14; P less than 0.01). Fourteen of the 63 patients with clinically nonfunctioning tumors (22%) had elevated serum alpha-subunit levels in the monoclonal assay vs. 11 (17%) in the polyclonal assay. Among the 19 patients with acromegaly, the prevalence was 7 (37%) and 3 (16%) using the monoclonal and polyclonal assays, respectively. Twenty-eight (44%) of the patients with clinically nonfunctioning pituitary adenomas were female. Eleven (39%) of the women were under 45 yr old, as were 10 (29%) of the men. We conclude that the prevalence of free alpha-subunit hypersecretion in patients with clinically nonfunctioning and somatotroph adenomas may be higher than previously recognized, and that a sensitive and specific monoclonal antibody free alpha-subunit assay may provide a useful tumor marker in these patients. The prevalence of clinically nonfunctioning pituitary tumors among younger men and women may also have been previously under-estimated.


Renin-angiotensin system, blood pressure homeostasis and renal function in galactosamine-induced fulminant hepatic failure in the guinea pig.
Arterial blood pressure, renal function and plasma concentrations of renin and renin substrate (angiotensinogen) were investigated in guinea pigs subjected to galactosamine-induced (1 g/kg i.v.) liver cell necrosis. Blood pressure declined continuously by 50% during a follow-up period of 72 h which was associated with a decrease in diuresis and natriuresis to 36 and 31%, respectively. Simultaneously, plasma renin concentration increased 30-fold indicating marked reduction of renal perfusion, while plasma renin substrate concentration fell to 6% of the baseline level. There was microscopic evidence of oligemic circulatory renal damage characterized by acute proximal tubular necrosis with concomitant tubular dilatation. Short-term infusion of homologous renin substrate-enriched plasma, derived from nephrectomized animals, was followed by marked increase in mean arterial blood pressure from 34 +/- 9 to 77 +/- 7 mm Hg accompanied by marked diuresis and natriuresis. Renin substrate depletion following galactosamine-induced fulminant liver failure may represent impaired hepatic biosynthesis as well as increased renin substrate consumption due to excessive renin secretion. Angiotensinogen repletion has a beneficial effect on both renal function and blood pressure probably due to marked generation of the potent vasoconstrictor angiotensin II which consequently inhibits renin secretion. These observations strongly support the suggestion that the renin-angiotensin system is of major importance to cardiovascular homeostasis in acute liver failure.


Impact of Social Networking Sites on Children in Military Families.
Youth in military families experience a relatively unique set of stressors that can put them at risk for numerous psychological and behavior problems. Thus, there is a need to identify potential mechanisms by which children can gain resiliency against these stressors. One potential mechanism that has yet to be empirically studied with military youth is social networking sites (SNSs). SNSs have gained significant popularity among society, especially youth. Given the significance of these communication tools in youths' lives, it is important to analyze how SNS use may affect military youth and their ability to cope with common military life stressors. The current review examines the potential positive and negative consequences associated with SNS use in coping with three common stressors of youth in military families: parent deployment, frequent relocation, and having a family member with a psychological or physical disability. By drawing from SNS and military literature, we predict that SNS use can be a positive tool for helping children in military families to cope with stressors. However, certain SNS behaviors can potentially result in more negative outcomes. Recommendations for future research are also discussed.


Phonological Short-term Memory and its Relationship to Language in Williams Syndrome.
Williams syndrome (WS), a rare neurodevelopmental disorder of genetic origin, is characterised by a relative advantage of language over more serious deficits in other cognitive domains. In this study the relationship of phonological short-term memory to WS language, in particular vocabulary, was explored. Using Gathercole and Baddeley's Children's Test of Nonword Repetition (CNRep) (Gathercole & Baddeley, 1996), we examined the pattern of performance by WS participants on that task and compared it to performance on measures of receptive language, visuospatial ability, and digit span. In addition, a comparison was made of WS nonword repetition score with those of two groups of individually matched normally developing 5-year-olds, one on the basis of nonverbal test age and the other on the basis of verbal test age. As expected WS repetition scores showed an effect of nonword length but not of phonological complexity. Nonwords that were relatively wordlike were better repeated than nonwords that were less wordlike. CNRep scores were correlated with test ages on TROG, Ravens, and digit span but not with chronological age. Test age on the CNRep was at a similar level to that on TROG, Ravens, and digit span but significantly lower than on BPVS. The results lend support to the view that phonology in WS is a relative strength. In contrast, despite relatively good productive and receptive vocabulary, certain aspects of the processes of word learning in WS do not seem to develop beyond that of normal 4year-olds. The good vocabulary scores of older children and adults with WS may be simply due to their relatively good phonological short-term memory.


Black widow spider bite.
Latrodectus mactans has now invaded towns and cities. The spider's venom is a neurotoxin that causes little local reaction but produces pain and spasm in large skeletal muscle groups within 30 minutes to three hours after the bite. Severe envenomation may result in respiratory failure and coma. First aid is of no value. Muscle relaxants are useful in treatment, as is calcium gluconate. Antivenin is indicated for high-risk victims, such as those with hypertension and persons younger than 16 or older than 60 years of age.


Quantitative morphological assessment of erythroblastic differentiation induced, in vitro, in human K562 leukemic cells.
K562 human leukemia cell line undergoes in vitro terminal differentiation towards the erythroid pathway following treatments with appropriate chemical agents including aclacinomycin, fagaronine and hemin. These three drugs induced a different expression of phenotypic and functional characters associated with differentiation. The morphological characteristics of the differentiation sequences elicited by these agents were evaluated by image analysis using a SAMBA 200 cell image processor. Multivariate statistical analyses of morphological data revealed that only aclacinomycin was able to induce significant modifications of the morphological parameters similar to those observed during the maturation of normal bone-marrow erythroblastic cells. These data correlate with the higher inductive potency of aclacinomycin as compared to hemin or fagaronine and suggest that quantitative cytology may be a useful adjunct to conventional tests for the selection of new drugs with differentiating potential.


'Imi Hale: establishing an inheritance for Native Hawaiians on cancer awareness, research and training.
Native Hawaiians experience disproportionate rates of cancer incidence and mortality both nationally and in their homeland, Hawai'i. 'Imi Hale--the Native Hawaiian Cancer Awareness, Research, and Training Project, a five-year project funded by the National Cancer Institute, is aimed at reducing the burden of cancer among Native Hawaiians. The project's overall goal is to reduce cancer incidence and mortality among Native Hawaiians through the establishment of a sustainable infrastructure to 1) promote cancer awareness within Native Hawaiian communities, and 2) initiate cancer research, training, and control activities. A community-based project, 'Imi Hale emphasizes community participation, respect for cultural values, and the sharing of information, as we believe that a commitment to involve Native Hawaiians in all activities of the project will help assure that the community's awareness, training, and research priorities are addressed. In the first year of operation, cancer awareness activities included the development of culturally sensitive booklets on breast cancer and the provision of cancer education and screening for members of the Association of the Hawaiian Civic Clubs. Research and training activities included focus groups to explore the perceptions and experiences of cancer survivors, surveys to assess research priorities, the identification of Native Hawaiian researchers and the development of pilot research projects. The work of 'Imi Hale is guided by the hope that Native Hawaiians can reverse the negative effects of cancer and leave a powerful legacy and inheritance for future generations based on good health and well-being. 'Imi Hale means "to establish, as a dynasty; to acquire authority, power; to seek and establish an inheritance for one's children; and to form a friendship so close that one feels welcome in the house of the other." "By using our language for a name, we are invoking and honoring our ancestors, our culture, language and restoration as a nation."


The genetics of Crohn's disease and ulcerative colitis--status quo and beyond.
The two major subtypes of inflammatory bowel disease (IBD), ulcerative colitis (UC, MIM#191390) and Crohn's disease (CD, MIM#266600), are chronic relapsing-remitting inflammatory disorders affecting primarily the gastrointestinal tract. Prevalence rates in North America and Europe range from 21 to 246 per 100,000 for UC and 8 to 214 per 100,000 for CD. Although CD and UC share some clinical and pathological features, they can be distinguished by localization, endoscopic appearance, histology and behavior, which suggest differences in the underlying pathophysiology. The importance of genetic risk factors in disease etiology is high and has been documented more clearly for CD than for UC (relative sibling risks λ(s): 15-35 for CD, 6-9 for UC). The most recent and largest genetic association study for IBD, which employed genome-wide association data for over 75,000 patients and controls, established the association of 163 susceptibility loci with IBD. Although the disease variance explained by the 163 loci only amounts to 13.6% for CD and 7.5% for UC, the identified loci and the candidate genes within yielded valuable insights into the pathogenesis of IBD and the relevant disease pathways. We here review the current research on the genetics of IBD and provide insights into on current efforts as well as suggest topics for future research.


Rejection and redistribution of scattered radiation in scan equalization digital radiography (SEDR): simulation with spot images.
The anti-scatter grid has been widely used to reject scatter and increase the perceptibility of a low-contrast object in chest radiography; however, it also attenuated the primary x-rays, resulting in a substantial loss of information and an increased relative noise level in heavily attenuated regions. A more dose efficient approach to scatter rejection is the slot-scan imaging technique. Another problem in chest radiography is the low transmitted x-ray intensity in heavily attenuating regions. It results in a higher relative noise level, thus limiting the contrast sensitivity. A solution to this problem is through the exposure equalization technique, with which the incident x-ray intensity is regionally modulated to compensate for the differences of x-ray attenuation due to the anatomic variation. We are in the process of implementing the scan equalization digital radiography (SEDR) technique, which combines the advantages of slot-scan imaging and exposure equalization. However, associated with the use of exposure equalization is a redistribution of scattered radiation at the detector, which may impact on the benefit of using exposure equalization in conjunction with the slot-scan imaging geometry. In order to understand the scatter properties and their impact in SEDR, we have used spot collimated digital radiographic images to synthesize simulated SEDR images with which scatter components, primary signals, and scatter-to-primary ratios (SPRs) were measured. It was shown that the anti-scatter grid rejected approximately 70% and 80% of scattered radiation in lightly and heavily attenuated regions, respectively, while the slot-scan method can reject as high as 95% (with 1 cm slot width) of scattered radiation without attenuation of the primary x-rays. Using a simple model for scatter effects, we have also estimated and compared the contrast-to-noise ratio degradation factors (CNRDFs, i.e., the fraction by which CNR is reduced). It was found that for quantum limited situations, the slot-scan technique has resulted in a substantial improvement of the image quality, as indicated by higher estimated CNRDFs (less scatter). An estimated improvement of 40%-50% in the lungs, 50%-90% in the mediastinum, and 60%-110% in the subdiaphragm was achieved with the slot-scan over the anti-scatter grid method. Compared to slot-scan imaging, SEDR resulted in higher SPRs in the lungs and lower SPRs in the mediastinum. In the subdiaphragmatic regions, the SPRs remain about the same. This corresponds to lower CNRDFs in the lungs, higher CNRDFs in the mediastinum, and about the same CNRDFs in the subdiaphragmatic regions. It was shown that although SEDR has resulted in minimum improvement over slot-scan imaging in reducing the SPRs, it could improve the contrast sensitivity by raising the primary signal levels in heavily attenuating regions. This advantage needs to be further investigated in our continuing study of the SEDR technique.


Laptop computer induced erythema ab igne: a new presentation of an old disease.
Erythema ab igne is a condition characterized by skin changes due to chronic exposure to moderate temperature. We describe a female patient with continuous use of a laptop computer on exposed legs for 6 months and consequent development of reticulated hyperpigmentation at the area. Histopathological examination revealed epidermal atrophy, collagen fragmentation, and vacuolar changes in the basal layer, among other signs. We consider this case to be a modern cause of erythema ab igne.


Using the Mixed Rasch Model to analyze data from the beliefs and attitudes about memory survey.
In this study, we used the Mixed Rasch Model (MRM) to analyze data from the Beliefs and Attitudes About Memory Survey (BAMS; Brown, Garry, Silver, and Loftus, 1997). We used the original 5-point BAMS data to investigate the functioning of the "Neutral" category via threshold analysis under a 2-class MRM solution. The "Neutral" category was identified as not eliciting the model expected responses and observations in the "Neutral" category were subsequently treated as missing data. For the BAMS data without the "Neutral" category, exploratory MRM analyses specifying up to 5 latent classes were conducted to evaluate data-model fit using the consistent Akaike information criterion (CAIC). For each of three BAMS subscales, a two latent class solution was identified as fitting the mixed Rasch rating scale model the best. Results regarding threshold analysis, person parameters, and item fit based on the final models are presented and discussed as well as the implications of this study.


Frequent detection and immunophenotyping of prostate-derived cell clusters in the peripheral blood of prostate cancer patients.
Recent scientific studies have failed to determine parameters for the assessment of prostate cancer aggressiveness. The present study deals with the detection of blood-borne cancer cells based on polymerase chain reaction (PCR) and cell enrichment methods. The contradictory results reported in the literature have called into question the clinical usefulness of this diagnostic method in the preoperative staging of clinically localized prostate cancer. We established a combined method of density gradient centrifugation and immunomagnetic separation using epithelium-specific antibodies, i.e. cytokeratins, to isolate prostate-derived circulating cells from the peripheral blood of patients with prostate cancer. Isolated cells were characterized by DNA staining and immunocytochemistry using antibodies for the detection of prostate-specific antigen (PSA), proliferation-associated proteins (MIB-1, H1 and H3) and apoptosis-associated proteins (M30, c-FasR). We applied these methods to 68 prostate cancer patients and were able to isolate cell clusters in 98%. Immunophenotypic and morphological characterization of PSA-positive prostate-derived cell clusters found in the peripheral blood of prostate cancer patients showed two main populations: 1) in 35% of the investigated prostate cancer patients we detected rounded cell aggregates of probable cancer cells expressing proliferation-associated proteins and lacking apoptosis-associated protein expression; 2) in all cases there was a high frequency of circulating dysmorphic cell clusters positive for apoptosis-associated protein expression. Our results demonstrate the existence of at least two different types of blood-borne prostate-derived circulating cell clusters. Of these, only the less frequent, round, small cell clusters harbor features that are probably necessary for the cells to survive for metastatic spread.


Sexual and reproductive health service utilisation of adolescents and young people from migrant and refugee backgrounds in high-income settings: a qualitative evidence synthesis (QES).
Young people with migrant or refugee backgrounds from low- and middle-income countries settle in high-income countries and tend to underutilise sexual and reproductive health (SRH) services. This review aimed to explore perceptions and experiences of SRH services and the factors that shape their use among migrant youth. It focuses on qualitative studies that examine SRH service use among young migrants living in high-income countries. Seven peer-review databases and web-based grey literature were searched using pre-determined search criteria. The review includes 16 articles that met the inclusion criteria. The qualitative evidence synthesis (QES) method was used to synthesise findings. Thematic analysis resulted in five main themes and 11 sub-themes. Findings suggest that despite diversity of countries of origin and host countries, there were considerable similarities in their perceptions of and experiences with SRH services. Some young migrants reported experiences of discrimination by service providers. Cost of care was a deterrent to SRH service use in countries without universal healthcare coverage. Lack of information about SRH services, concerns about confidentiality, community stigma around sexually transmitted infections and premarital sex were key barriers to SRH service use. Health systems should integrate flexible service delivery options to address access barriers of SRH service use in young migrants. Engagement with parents and communities can help to destigmatise sexual health problems, including STIs. Host countries need to equip young migrants with the knowledge required to make informed SRH decisions and access relevant SRH services and resources.


The Neuropsychiatric Inventory--NPI. Validation of the Danish version.
Assessment of neuropsychiatric symptoms in dementia has great clinical importance. The aim of the study was validation of the Danish version of the NPI, using assessments of 72 demented and 29 non-demented of age 65+ years and their caregivers at three visits. The NPI was administered by the same psychiatric nurse interviewing the same caregiver. At visits 1 and 3, a psychogeriatrician assessed the participant using the ICD-10, the Geriatric Deterioration Scale (GDS) and the Clinical Global Impression (CGI) as well as the NPI in a visual analogue scale (VAS) version. These scores were blindly converted into scores equalling the frequency and severity of the NPI by one of the investigators. Data analysis comprised inter-rater reliabilities (intra-class coefficients, ICC); NPI scores and corresponding VAS scores were compared using Spearman's correlation coefficients. NPI scores at visits 1 and 2 were used to assess the test-retest reliabilities. The scalability of the NPI was assessed with Mokken and Loevinger coefficients. The ICC for all the NPI domains and the GDS (>0.80) were perfect, the ICC for the NPI-VAS (0.68-0.95) and the CGI (0.69) was satisfactory to perfect. Correlations between NPI and NPI-VAS were high; only two domains had coefficients below 0.60: depression and agitation/aggression. NPI-total scores increase with increasing severity of dementia. The NPI did not fulfil the scalability assessed by the Mokken and Loevinger coefficients. The NPI Danish version is valid and reliable in assessing neuropsychiatric symptoms in dementia but not fully scalable. The use of single item scores and not total sum score is recommended.


Screening for distant metastases in patients with head and neck cancer: is chest computed tomography sufficient?
The detection of distant metastases during screening influences the choice of treatment in patients with head and neck squamous cell carcinoma. A previous study in the authors' institution showed that chest computed tomography (CT) scan was the most important screening technique. Different clinical risk factors in patients with head and neck squamous cell carcinoma for the development of distant metastases were identified. Retrospective cohort study. To evaluate the authors' diagnostic strategy, the accuracy of screening for distant metastases with chest CT in 109 consecutive patients with head and neck squamous cell carcinoma with risk factors between 1997 and 2000 was retrospectively analyzed. Preoperative screening with CT revealed 20 patients (18%) with lung metastases and 1 liver metastasis. Despite negative screening with chest CT, 9 (11%) patients developed distant metastases within 12 months during follow-up. Sensitivity of the chest CT was 73%; the specificity was 80%. Although chest CT frequently detects distant metastases, there seems to be a need for a more sensitive and whole-body screening technique.


Insulin absorption and subcutaneous blood flow in normal subjects during insulin-induced hypoglycemia.
We studied the effects of insulin-induced hypoglycemia on the absorption of 10 U 125I-labeled soluble human insulin injected sc in the thigh in 10 normal subjects. The disappearance of 125I from the injection site was followed by external gamma-counting. Subcutaneous blood flow (ATBF) was measured concomitantly with the 133Xe washout technique. The plasma glucose nadir [mean, 2.0 +/- 0.1 (+/- SE) mmol/L] occurred at 33 +/- 3 min and resulted in maximal arterial plasma epinephrine concentrations of approximately 6 nmol/L. From 30 min before to 60 min after the glucose nadir the [125I]insulin absorption rate was depressed compared to that during normoglycemia. The first order disappearance rate constants were reduced by approximately 50% (P less than 0.01) during the first 30-min interval after the glucose nadir. During the same period ATBF increased by 100% (P less than 0.05). The results suggest that in normal subjects the absorption of soluble insulin from a sc depot is depressed in connection with hypoglycemia, despite considerably elevated ATBF.


Reliability and validity of late vertex-evoked response audiometry.
In order to evaluate the current visual scoring technique in the late vertex-evoked response audiometry (ERA), the detectability of the response, errors in judgment, consistency between scorers and test-retest reliability were studied in adults and young children in waking and sleeping states. In waking adults, ERA proved to be a quite reliable and valid method for testing hearing objectively. On the contrary, a marked inconsistency was found in the appearance of the response in children during sleep. From a clinical standpoint, ERA in waking adults and sleeping children should be regarded as two substantially different methods.


Oxidation of copper nanoparticles in water: mechanistic insights revealed by oxygen uptake and spectroscopic methods.
Oxidation of aqueous ∼8 nm unprotected copper nanoparticles takes place under air in approximately 2 hours at 30 °C to give Cu(2+) as a final product through an intermediate Cu(+) species. At 5 °C the process is about 5 times slower; similarly, vitamin C, which plays a sacrificial role, also slows down the oxidation, while CuNP catalyses the oxidation. In this work, we present a detailed analysis of the oxidation mechanism of colloidal CuNP inferred through spectroscopic methods (UV-visible and EPR) combined with oxygen uptake measurements, with emphasis on factors affecting the oxidative process.


Conversion of methamphetamine to N-methyl-methamphetamine in formalin solutions.
Embalming is common, and yet it can create problems for the forensic scientist if a drug has been the cause of death and if this drug is also reactive toward the embalming fluid. Previous studies have focused on the amines such as nortriptyline, desipramine, and fenfluramine. In the presence of formalin, a typical component of embalming fluid, these compounds can be rapidly converted to their methylated derivatives amitriptyline, imipramine, and N-methyl-fenfluramine, respectively. We have begun a larger project designed to determine the reactivity and reactions of a wide range of drugs with formalin and have extended it to amphetamines. We report here our results from methamphetamine, which is converted into its N-methyl derivative in the presence of formalin. The rate of conversion is dependent upon pH and formalin concentration with the greatest conversion occurring under basic conditions and the highest formalin concentration. Up to 100% conversion in 24 h was observed under certain conditions. When studied in human tissue exposed to methamphetamine and treated with formalin, again, conversion to N-methyl-methamphetamine was readily apparent as early as 30 min after exposure to formalin. Finally, we note that the reactions of methamphetamine with formalin studied here are probably general and should be considered when performing postmortem/postembalming forensic analysis.


Feasibility and outcome of reproducible clinical interpretation of high-dimensional molecular data: a comparison of two molecular tumor boards.
Structured and harmonized implementation of molecular tumor boards (MTB) for the clinical interpretation of molecular data presents a current challenge for precision oncology. Heterogeneity in the interpretation of molecular data was shown for patients even with a limited number of molecular alterations. Integration of high-dimensional molecular data, including RNA- (RNA-Seq) and whole-exome sequencing (WES), is expected to further complicate clinical application. To analyze challenges for MTB harmonization based on complex molecular datasets, we retrospectively compared clinical interpretation of WES and RNA-Seq data by two independent molecular tumor boards. High-dimensional molecular cancer profiling including WES and RNA-Seq was performed for patients with advanced solid tumors, no available standard therapy, ECOG performance status of 0-1, and available fresh-frozen tissue within the DKTK-MASTER Program from 2016 to 2018. Identical molecular profiling data of 40 patients were independently discussed by two molecular tumor boards (MTB) after prior annotation by specialized physicians, following independent, but similar workflows. Identified biomarkers and resulting treatment options were compared between the MTBs and patients were followed up clinically. A median of 309 molecular aberrations from WES and RNA-Seq (n = 38) and 82 molecular aberrations from WES only (n = 3) were considered for clinical interpretation for 40 patients (one patient sequenced twice). A median of 3 and 2 targeted treatment options were identified per patient, respectively. Most treatment options were identified for receptor tyrosine kinase, PARP, and mTOR inhibitors, as well as immunotherapy. The mean overlap coefficient between both MTB was 66%. Highest agreement rates were observed with the interpretation of single nucleotide variants, clinical evidence levels 1 and 2, and monotherapy whereas the interpretation of gene expression changes, preclinical evidence levels 3 and 4, and combination therapy yielded lower agreement rates. Patients receiving treatment following concordant MTB recommendations had significantly longer overall survival than patients receiving treatment following discrepant recommendations or physician's choice. Reproducible clinical interpretation of high-dimensional molecular data is feasible and agreement rates are encouraging, when compared to previous reports. The interpretation of molecular aberrations beyond single nucleotide variants and preclinically validated biomarkers as well as combination therapies were identified as additional difficulties for ongoing harmonization efforts.


[A micromanipulator for the microscope photometer].
A micromanipulator is described to be designed for micro-operations on cells and for various cytological investigations using microelectrodes especially when cell scanning with inserted microinstrument is required. The baseplate of positioners is a light plate located on the microscope stage immediately. Thus, it is possible to do the following operations: to move the object in the field of vision of the microscope simultaneously with the inserted instrument; to insert several microinstruments into one cell; to make photometry of the cell with the inserted instrument by the scanning method. The positioners bear mechanical micromanipulator which ensures the moving of the instrument in three coordinates (8 mm lengthwise, 3 mm crosswise, and 4 mm in upright position). The micromanipulator can be employed with any type of biological microscopes and makes it possible to use objectives of high magnification (up to 100x). A little weight of the instrument (1 kg) makes it convenient to be used in the expedition.


Antrodia camphorata polysaccharides exhibit anti-hepatitis B virus effects.
Polysaccharides were extracted from fruiting bodies and cultured mycelia from five Antrodia camphorata strains. Polysaccharide profiles of the five strains, as determined by high-performance anion-exchange chromatography, showed varying yields and composition of neutral sugars. A. camphorata fruiting bodies also had different polysaccharide patterns compared to the cultured mycelium. Analysis of 26-day-old mycelia showed that the neutral sugars galactose, glucose, mannose, and galactosamine were predominant. All mycelia polysaccharide preparations exhibited anti-hepatitis B virus activity. Polysaccharides from strain B86 at a concentration of 50 microg ml(-1) showed the highest level of anti-hepatitis B surface antigen effect, which was higher than alpha-interferon at a dosage of 1000 U ml(-1). Only strains B86 and 35398 had substantial anti-hepatitis B e antigen activities. None of the polysaccharides exhibited cytotoxic effects.


Identification and characterization of Bimgamma, a novel proapoptotic BH3-only splice variant of Bim.
BH3 (Bcl-2 homology 3)-only proteins of the Bcl-2 family play an essential role in apoptosis. In this study, a novel human BH3-only protein, Bcl-2-interacting mediator (Bim)gamma, was identified during our study of regulation of prostate cancer cell death by Bcl-2 family proteins. Bimgamma shares the highest amino acid sequence homology to BimEL and BimL, two proapoptotic BH3-only Bcl-2 proteins derived from alternative mRNA splicing. Genomic studies indicate that Bimgamma is a novel splice variant of Bim and is generated as a result of the retention of a 126-bp intron of the bim gene. Bimgamma mRNA displays a tissue-specific expression pattern distinct from those of the other Bim isoforms. Subcellular fractionation studies indicate that Bimgamma is localized both in intracellular membranes and cytosol. Interestingly, Bimgamma mRNA, similar to the BimEL protein, is up-regulated in the majority of the prostate cancer cell lines studied, whereas several other proapoptotic Bcl-2 proteins, including Bax, Bak, and Bad, are down-regulated in prostate cancer cells. Functional studies indicate that Bimgamma inhibits clonal growth in prostate cancer cells and promotes apoptosis, which is inhibited by overexpressing Bcl-2. Because both Bimgamma and BimEL are proapoptotic BH3-only proteins and both are up-regulated in prostate cancer cells, they may play a unique role in prostate cancer development.


Patient and family attitudes toward schizophrenia treatment.
Patient and family member attitudes toward illness, psychopharmacologic and nonpharmacologic treatments in schizophrenia, as well as their attitudes toward psychiatric research are reviewed here. The authors' recent work investigating patient and family member attitudes toward illness, medication, and a new method of receiving medication via surgical implants is also presented. The authors highlight the importance of understanding patient attitudes so that individual treatment plans and new treatments for schizophrenia can be facilitated. The important contribution of family members in caring for their loved ones is also emphasized. Patient participation in biomedical research is also discussed in the context of guiding the treatment of schizophrenia.


[Second year nursing students' identity crisis. "Assessment of objectives"].
Nursing students, guided by aspirations, begin training with an idealized representation of the profession, and the experiences they will encounter during their studies will vary progressively. Nursing training is based initially on a pedagogical system alternating between the classroom and the work place, exposing the student to a variety of situations. This process of work experience during the three years of study is marked by a crisis period during the second year. This involves an identity crisis resulting in a change of objectives. The analysis indicates that this is structural. The beginning of the second year is characterised by the student's confrontation with the theoretical and practical applications of the course. It is the result of a year's experience and instruction, which puts into question the student's vision, beliefs, and the orientation towards a new conception of himself/herself and of the world. The realisation of an incongruity, this reality check, is followed by a feeling of deception. This conflict, common in the second year, must be recognised in order to avoid further compromise to the identity's transformation. As soon as the student finds himself/herself committed to a training program that does not contribute to the realisation of his/her objectives, the feeling of being thrown off balance in relation to his/her point of reference increases, and the end result will be absenteeism or opposition. The handling of this identity crisis, as well as the motivational procedure, implies a modification in the quality of the instructor and in our way of thinking and acting. Are we adequately prepared to manage this crisis? Do we have access to the theories needed to resolve this cognitive conflict?


[arg-13 is implicated in mitochondrial ornithine transport in Neurospora crassa].
arg-13 is a leaky mutation involved in arginine metabolism. A tight selection is developed using similar amount of lysine and ornithine replacing other nitrogen source in minimal medium. This selection strongly inhibits the growth of arg-13 under stringent sorbose/glucose condition but allows arg-13 to grow under spot test conditions. As ornithine is build up through mitochondrial ornithine biosynthesis and transport from cytoplasm to mitochondria, arg-13 is combined in genetic crosses with arg-4 which blocks mitochondrial ornithine synthesis. Under spot test conditions, double mutant arg-4, arg-13 is able to use ornithine as sole nitrogen source and arginine biosynthesis precursor, but subject to strong lysine and canavanine inhibition. While the usage of ornithine in arg-4 single mutant with intact ornithine transport function is only slightly inhibited by lysine. All available data suggest arg-13 plays a major role in mitochondrial ornithine transport. The strain carrying the mutation at the arg-13 locus allows inefficient mitochondrial ornithine trafficking, possibly mediated by another distinct basic amino acid carrier.


National trends in off-label use of atypical antipsychotics in children and adolescents in the United States.
The objectives of the study were as follows: to examine the national trend of pediatric atypical antipsychotic (AAP) use in the United States; to identify primary mental disorders associated with AAPs; to estimate the strength of independent associations between patient/provider characteristics and AAP use. Data are from the National Ambulatory Medical Care Survey and the National Hospital Ambulatory Medical Care Survey. First, average AAP prescription rates among 4 and 18-year-old patients between 1993 and 2010 were estimated. Second, data from 2007 to 2010 were combined and analyzed to identify primary mental disorders related to AAP prescription. Third, a multivariate logistic regression model was developed having the presence of AAP prescription as the dependent variable and patient/provider characteristics as explanatory variables. Adjusted odds ratios (AORs) with associated 95% confidence intervals (CIs) were estimated. Outpatient visits including an AAP prescription among 4 to 18-year-old patients significantly increased between 1993 and 2010 in the United States, and over 65% of those visits did not have diagnoses for US Food and Drug Administration-approved AAP indications. During 2007 to 2010, the most common mental disorder was attention-deficit hyperactivity disorder, accounting for 24% of total pediatric AAP visits. Among visits with attention-deficit hyperactivity disorder diagnosis, those with Medicaid as payer (AOR 1.66, 95% CI 1.01-2.75), comorbid mental disorders (e.g., psychoses AOR 3.34, 95% CI 1.35-8.26), and multiple prescriptions (4 or more prescriptions AOR 4.48, 95% CI 2.08-9.64) were more likely to have an AAP prescription. The off-label use of AAPs in children and adolescents is prevalent in the United States. Our study raises questions about the potential misuse of AAPs in the population.


In-situ electro-generation and activation of hydrogen peroxide using a CuFeNLDH-CNTs modified graphite cathode for degradation of cefazolin.
The modified multifunctional electrodes for electro-Fenton (EF) process are suggested to be promising cathodes for in situ electro-generation and activation of H2O2 to produce hydroxyl radicals (•OH). However, heterogeneous EF process still faces the challenges of limited catalytic activity and releasing of massive amounts of transition metals to the solution after removal of organic pollutants. The main aim of the present investigation was to prepare a cathode containing carbon nanotubes (CNTs) and CuFe nano-layered double hydroxide (NLDH) for degradation and mineralization of cefazolin antibiotic through electro-Fenton process. Structural and electrochemical analyses demonstrated that CuFeNLDH-CNTs nanocomposite was successfully incorporated on the surface of graphite cathode. Due to the increased formation of •OH in the reactor, the incorporation of CNTs into NLDH matrix with a catalyst loading of 0.1 g substantially improved the degradation efficiency of cefazolin (89.9%) in comparison with CNTs-coated (28.7%) and bare graphite cathode (22.8%) within 100 min. In the presence of 15 mM of ethanol, the degradation efficiency of cefazolin was remarkably decreased to 43.7% by the process, indicating the major role of •OH in the destruction of target molecules. Acidic conditions favored the degradation efficiency of cefazolin by the modified EF process. Mineralization efficiency of the bio-refractory compound was obtained to be 70.1% in terms of chemical oxygen demand (COD) analysis after 300 min. The gas chromatography-mass spectroscopy (GC-MS) analysis was also implemented to identify the intermediate byproducts generated during the degradation of cefazolin in the CuFeNLDH-CNTs/EF reactor.


Low-dose oral hydroxychloroquine led to impaired vision in a child with renal failure: Case report and literature review.
Hydroxychloroquine (HCQ) has received much attention in the treatment of coronavirus disease 2019 recently. However, it can cause irreversible vision loss. Few cases have been reported in pediatric patient with HCQ-related adverse reactions. Appropriate administration and early disease recognition are important for reducing the adverse drug reactions of HCQ. We report a case of a 14-year-old Chinese girl who sought treatment for rapidly decreasing vision in the left eye over 3 days. The simulation results of the population pharmacokinetic model of HCQ revealed that the plasma concentration of HCQ abnormally increased before the visual acuity of the eye decreased. She was diagnosed as HCQ related drug adverse reaction. The daily dose of HCQ for this patient was adjusted from 100 mg/d to 50 mg/d. Follow-up for 6 months showed no more vision loss recurrence. However, the existing decreased visual acuity of the eye did not recover either. Although decreased visual acuity is an infrequent symptom, ophthalmologists should be aware of the possibility of HCQ concentration enrichment and consider minimizing HCQ use when a child with renal hypofunction seeks treatment for shortsightedness.


Fluoroquinolones and the risk of aortopathy: A systematic review and meta-analysis.
To investigate the association between fluoroquinolones use and development of aortopathy. A systematic review and meta-analysis was conducted following PRISMA and MOOSE guidelines for reporting systematic reviews of observational studies. Multiple databases were searched and two authors independently screened studies for eligibility. Newcastle Ottawa scale was used to assessed the quality of included studies. Primary outcome of interest was development of aortic aneurysm or dissection among fluoroquinolones users in comparison to non-users. An inverse variance model meta-analysis was used to pool odds ratio or hazards ratio from included studies to calculate the overall effect estimate. Pre specified subgroups analyses were also conducted to explore sources of heterogeneity. Three observational studies that enrolled 941,639 subjects met the inclusion criteria and were included in the final analysis. All studies were of a good methodological quality. Current use of fluoroquinolones, defined as within 60 days from development of the primary outcome, was associated with significantly elevated risk of developing aortic aneurysm and/or dissection in comparison to controls, (OR = 2.04; 95% CI [1.67, 2.48]). There was only a mild degree of between study heterogeneity, I2 = 33%. The association remains robust among all subgroups analyses. Our findings indicate that current fluoroquinolone use was significantly associated with increased risk of aortic aneurysm and dissection. Health care providers need to be aware of this serious association and use fluoroquinolones judiciously in order to minimize the risk of the serious sequela of aortopathy.


Evaluation of response to stereotactic body radiation therapy for nonsmall cell lung cancer: PET response criteria in solid tumors versus response evaluation criteria in solid tumors.
Recommendations for surveillance after stereotactic body radiation therapy (SBRT) for early-stage nonsmall cell lung cancer (NSCLC) are not well defined. Recently, PET response criteria in solid tumors (PERCIST) have been proposed as a new standardized method to assess radiotherapeutic response both quantitatively and metabolically. The aim of this study was to evaluate therapeutic response following SBRT in early-stage NSCLC patients by comparing PERCIST with the currently widely used RECIST. Forty-nine patients with early-stage NSCLC who had been prescribed SBRT were studied. Responses of lesion were evaluated using CT and 18F-FDG PET according to the RECIST and PERCIST methods. PET-CT scans were obtained before SBRT and 3-6 months after SBRT. Associations between overall survival (OS) and clinicopathologic results (histology, tumor location, tumor size, lymphatic invasion, clinical stage, and radiotherapeutic responses in RECIST and PERCIST) were statistically analyzed. The median patient follow-up was 30 months. Thirteen patients had stage IA, 9 stage IB, 10 stage IIA, and 17 stage IIB biopsy-proven NSCLC. Three-year OS was 79.6%. CT scans indicated three regional recurrences. PET-CT/chest indicated three regional recurrences and distant metastasis. Significant differences were observed in response classification between RECIST and PERCIST (Wilcoxon signed-rank test, P = 0.0041). Univariate analysis showed that clinical stage, RECIST, and PERCIST were significant factors associated with OS, whereas by multivariate analysis PERCIST was the only predictor of OS. SMD, PMD/PMR, and CMR in PERCIST criteria were indicative of a 9.900-fold increase in the risk of OS in early NSCLC patients [risk ratio, 9.900 (95% CI, 1.040-21.591); P = 0.001]. RECIST based on the anatomic size reduction rate did not demonstrate the correlation between radiotherapeutic response and prognosis in patients with early-stage NSCLC receiving SBRT. However, PERCIST was shown as the strongest independent predictor of outcomes. PERCIST might be considered more suitable for the evaluation of NSCLC tumor response to SBRT than RECIST.


Saccharomyces boulardii decreases inflammation and intestinal colonization by Candida albicans in a mouse model of chemically-induced colitis.
The present study was designed to investigate the effects of Saccharomyces boulardii on inflammation and intestinal colonization by Candida albicans in a BALB/c mouse model of colitis that had been induced by dextran-sulfate-sodium (DSS). Colonization with C. albicans was established by oral gavage with a 200 microL suspension of 10(7) yeast cells. A 1.5% solution of DSS was administered in drinking water 1 h after C. albicans oral challenge, while 10(7) cells of S. boulardii was inoculated daily by oral gavage for 1 week. Faeces were collected daily for 2 weeks. Seven groups of mice consisting of those that were administered either C. albicans or S. boulardii or both were sacrificed after 14 days and samples of the colon were taken for histological scoring and real-time PCR (RT-PCR) analysis of inflammatory cytokines and toll-like receptors (TLRs). Compared to control animals that did not receive DSS, the number of C. albicans colonies recovered from faeces was significantly greater in mice receiving DSS. In contrast, the colony forming units (CFUs) of C. albicans were greatly reduced in mice receiving S. boulardii. The administration of this yeast decreased the severity of DSS-induced clinical scores and histological inflammation. At the mRNA expression level, an increase in TLR2 and TLR4 resulting from the presence of S. boulardii was associated with a reduction in the inflammatory cytokines TNFalpha and INFgamma. In mice receiving DSS and C. albicans, TLR4 was over-expressed by stimulation with both yeasts, but TLR2 and TNFalpha, which were increased by the administration of C. albicans alone, were decreased in the presence of S. boulardii. These results indicate that S. boulardii decreased inflammation and C. albicans colonization in this BALB/c mouse model of colitis.


CPAP Devices for Emergency Prehospital Use: A Bench Study.
CPAP is frequently used in prehospital and emergency settings. An air-flow output minimum of 60 L/min and a constant positive pressure are 2 important features for a successful CPAP device. Unlike hospital CPAP devices, which require electricity, CPAP devices for ambulance use need only an oxygen source to function. The aim of the study was to evaluate and compare on a bench model the performance of 3 orofacial mask devices (Ventumask, EasyVent, and Boussignac CPAP system) and 2 helmets (Ventukit and EVE Coulisse) used to apply CPAP in the prehospital setting. A static test evaluated air-flow output, positive pressure applied, and FIO2 delivered by each device. A dynamic test assessed airway pressure stability during simulated ventilation. Efficiency of devices was compared based on oxygen flow needed to generate a minimum air flow of 60 L/min at each CPAP setting. The EasyVent and EVE Coulisse devices delivered significantly higher mean air-flow outputs compared with the Ventumask and Ventukit under all CPAP conditions tested. The Boussignac CPAP system never reached an air-flow output of 60 L/min. The EasyVent had significantly lower pressure excursion than the Ventumask at all CPAP levels, and the EVE Coulisse had lower pressure excursion than the Ventukit at 5, 15, and 20 cm H2O, whereas at 10 cm H2O, no significant difference was observed between the 2 devices. Estimated oxygen consumption was lower for the EasyVent and EVE Coulisse compared with the Ventumask and Ventukit. Air-flow output, pressure applied, FIO2 delivered, device oxygen consumption, and ability to maintain air flow at 60 L/min differed significantly among the CPAP devices tested. Only the EasyVent and EVE Coulisse achieved the required minimum level of air-flow output needed to ensure an effective therapy under all CPAP conditions.


Monostotic fibrous dysplasia of the clivus: image-guided endoscopic endonasal transsphenoidal surgery.
Fibrous dysplasia is a non-heritable, congenital disease involving the bones. Its diagnosis relies on image examination and pathology. Treatment is usually conservative, but in cases of cranial nerve impingement or extension to the condyles, surgery should be considered. In this paper, we describe a singular case of monostotic fibrous dysplasia of the clivus in a child. A 14-year-old boy presented with chronic headache and diplopia. A neurological examination revealed palsy of the right VIth cranial nerve. The radiological findings were consistent with fibrous dysplasia, with a hypointense and isointense clival lesion on T (1)- and T (2)-weighted images, respectively. Surgical treatment was indicated by cranial nerve impairment. An endoscopic endonasal approach with an image-guided system was used. The patient was discharged four days after surgery and his diplopia improved postoperatively. A variety of surgical approaches have been used in the treatment of midline extra-axial cranial base tumors. Fibrous dysplasia of the clivus without expansion to the condylus can be removed with a transsphenoidal endonasal endoscopic approach. Preoperative imaging reveals the individual patient's anatomy and improves the intraoperative orientation. Image-guided transsphenoidal endoscopic surgery is recommended for its safety and minimal invasiveness.


T Helper Lymphocyte and Mast Cell Immunohistochemical Pattern in Nonceliac Gluten Sensitivity.
Nonceliac gluten sensitivity (NCGS) is a gluten-related emerging condition. Since few data about NCGS histopathology is available, we assessed the markers of lymphocyte and innate immunity activation. We retrieved duodenal biopsy samples of patients with NCGS diagnosis according to the Salerno criteria. We selected specimens of positive (seropositive celiac disease/Marsh 1-2 stage) and negative (normal microscopic picture) controls. Immunohistochemistry for CD3 (intraepithelial lymphocytes-IELs), CD4 (T helper lymphocytes), CD8 (T cytotoxic lymphocytes), and CD1a/CD117 (Langerhans/mast cells) was performed. ANOVA plus Bonferroni's tests were used for statistical analysis. Twenty NCGS, 16 celiac disease, and 16 negative controls were selected. CD3 in NCGS were higher than negative controls and lower than celiac disease (18.5 ± 6.4, 11.9 ± 2.8, and 40.8 ± 8.1 IELs/100 enterocytes; p < 0.001). CD4 were lower in NCGS than controls and celiac disease (31.0 ± 22.1, 72.5 ± 29.5, and 103.7 ± 15.7 cells/mm2; p < 0.001). CD8 in NCGS were similar to negative controls, but lower than celiac disease (14.0 ± 7.4 and 34.0 ± 7.1 IELs/100 enterocytes, p < 0.001). CD117 were higher in NCGS than celiac disease and negative controls (145.8 ± 49.9, 121.3 ± 13.1, and 113.5 ± 23.4 cells/mm2; p = 0.009). The combination of CD4 and CD117, as well as IEL characterization, may be useful to support a clinical diagnosis of NCGS.


Lighting up cells: labelling proteins with fluorophores.
During the past decade, rapid improvements have been made in the tools available for labelling proteins within cells, which has increased our ability to unravel the finer details of cellular events. One significant reason for these advances has been the development of fluorescent proteins that can be incorporated into proteins by genetic fusion to produce a fluorescent label. In addition, new techniques have made it possible to label proteins with small organic fluorophores and semiconductor nanocrystals.


Development of a porcine small intestinal cDNA micro-array: characterization and functional analysis of the response to enterotoxigenic E. coli.
The intestine is a complex and dynamic ecosystem, in which nutrients, exogenous compounds and micro-flora interact, and its condition is influenced by the complex interaction between these factors and host genetic elements. Furthermore, interactions of immune cells with the other components of the intestinal mucosa are essential in the defense against pathogens. The outcomes of these complex interactions determine resistance to infectious diseases. The development of genomic tools and techniques allows for analysis of multiple and complex host responses. We have constructed a porcine small intestinal micro-array, based on cDNA from jejunal mucosal scrapings. Material from two developmental distinct stages (4- and 12-week-old pigs) was used in order to assure a reasonably broad representation of mucosal transcripts. The micro-array consists of 3468 cDNAs spotted in quadruplicate. Comparison of the 4-week-old versus 12-week-old pigs revealed a differential expression in at least 300 spots. Furthermore, we report the early gene expression response of pig small intestine jejunal mucosa to infection with enterotoxigenic E. coli (ETEC) using the small intestinal segment perfusion (SISP) technique. A response pattern was found in which a marker for innate defense dominated, demonstrating the strength of this applied technology. Further analysis of these response patterns will contribute to a better understanding of enteric health and disease in pigs. The great similarity between pig and human suggest results from these continuing studies should be applicable for both agricultural and human biomedical purposes.


Cytomegalovirus-Driven Adaptive-Like Natural Killer Cell Expansions Are Unaffected by Concurrent Chronic Hepatitis Virus Infections.
Adaptive-like expansions of natural killer (NK) cell subsets are known to occur in response to human cytomegalovirus (CMV) infection. These expansions are typically made up of NKG2C+ NK cells with particular killer-cell immunoglobulin-like receptor (KIR) expression patterns. Such NK cell expansion patterns are also seen in patients with viral hepatitis infection. Yet, it is not known if the viral hepatitis infection promotes the appearance of such expansions or if effects are solely attributed to underlying CMV infection. In sizeable cohorts of CMV seropositive hepatitis B virus (HBV), hepatitis C virus (HCV), and hepatitis delta virus (HDV) infected patients, we analyzed NK cells for expression of NKG2A, NKG2C, CD57, and inhibitory KIRs to assess the appearance of NK cell expansions characteristic of what has been seen in CMV seropositive healthy individuals. Adaptive-like NK cell expansions observed in viral hepatitis patients were strongly associated with CMV seropositivity. The number of subjects with these expansions did not differ between CMV seropositive viral hepatitis patients and corresponding healthy controls. Hence, we conclude that adaptive-like NK cell expansions observed in HBV, HCV, and/or HDV infected individuals are not caused by the chronic hepatitis infections per se, but rather are a consequence of underlying CMV infection.