Diagnostic Validity of Gastric Aspirate Culture in Nontuberculous Mycobacterial Pulmonary Disease.
Rationale: Although gastric aspirate culture is used for diagnosing pulmonary tuberculosis, its usefulness in diagnosing pulmonary infections of nontuberculous mycobacteria (NTM) is unknown.Objectives: To investigate the diagnostic validity of gastric aspirate culture for acid-fast bacilli in NTM pulmonary disease (NTM-PD).Methods: Gastric aspirates were collected from patients with suspected NTM-PD at the Osaka Toneyama Medical Center between December 2006 and February 2018. Patients with a final diagnosis of pulmonary tuberculosis, an observation period of less than 6 months, or fewer than three conducted sputum cultures were excluded from the study. NTM-PD was diagnosed as per American Thoracic Society/Infectious Diseases Society of America (ATS/IDSA) criteria. We retrospectively examined the diagnostic validity of gastric aspirate culture in Mycobacterium avium complex (MAC)-PD and M. kansasii-PD by comparing culture results with final diagnoses. This was done first for all patients, and subsequently for patients with negative results for early sputum cultures. In addition, we compared the time required for an NTM-PD diagnosis based on gastric aspiration with that based on ATS/IDSA criteria.Results: Among 475 total patients, 119 (25.1%) had positive NTM gastric aspirate cultures and 154 (32.4%) fulfilled the ATS/IDSA criteria for NTM-PD. The sensitivity, specificity, positive predictive value (PPV), and negative predictive values (NPVs) of gastric aspiration were 63.9%, 95.8%, 83.5%, and 88.8% in MAC-PD and 82.4%, 99.6%, 87.5%, and 99.3% in M. kansasii-PD, respectively. Sensitivity, specificity, PPV, and NPV of gastric aspirate cultures of the 378 patients who were undiagnosed based on sputum culture within 120 days were 34.0%, 95.5%, 51.6%, and 91.1% for MAC-PD and 75.0%, 99.5%, 60.0%, and 99.7% for M. kansasii-PD, respectively. Furthermore, gastric aspirate cultures tested in addition to bronchoscopy yielded incremental sensitivity of 8.7% (95.7% vs. 87.0%) and an NPV of 1.3% (99.3% vs. 98.0%) in MAC-PD. In patients with NTM-PD with NTM-positive gastric aspirate cultures, the period between gastric aspirate collection and the positive culture result was shorter than the time between gastric aspirate collection and NTM-PD diagnosis (6 [9-36] d vs. 25 [12-69] d, median [interquartile range], P < 0.0001].Conclusions: In settings where acid-fast bacilli pulmonary diseases are suspected, gastric aspirate culture may be helpful for diagnosing MAC-PD and M. kansasii-PD.


Treosulfan (dihydroxybusulphan) in the management of ovarian carcinoma.
Of 36 patients with ovarian carcinoma treated with treosulfan (dihydroxybusulphan) 30-5 per cent had a complete response for a mean of 19-0 months and 33-3 per cent had a partial response. Treosulfan may have a role in the management of ascites associated with ovarian neoplasm.


Histamine in the insect nervous system: distribution, synthesis and metabolism.
The distribution of histamine in the nervous systems of the locust, the cockroach, and the sphinx moth was mapped and the capacity of locust nervous tissue to synthesise and metabolise histamine was assessed. In all three species the highest levels of histamine were present in the retina and in the lamina neuropil of the optic lobe. Lower levels of histamine were detectable throughout the nervous system. In the locust the retina was shown to synthesise considerable quantities of histamine. The optic lobe and metathoracic ganglion synthesised smaller, though significant, amounts of histamine. Metabolic inactivation of histamine in locust nervous tissue was shown to occur primarily via oxidation to imidazole-4-acetic acid and via N-acetylation to N-acetyl histamine. Whereas the retina and the optic lobe formed the two metabolic products in approximately equal proportions, the metathoracic ganglion produced almost three times as much N-acetyl histamine as imidazole-4-acetic acid.


Chloroplast behaviour and interactions with other organelles in Arabidopsis thaliana pavement cells.
Chloroplasts are a characteristic feature of green plants. Mesophyll cells possess the majority of chloroplasts and it is widely believed that, with the exception of guard cells, the epidermal layer in most higher plants does not contain chloroplasts. However, recent observations on Arabidopsis thaliana have shown a population of chloroplasts in pavement cells that are smaller than mesophyll chloroplasts and have a high stroma to grana ratio. Here, using stable transgenic lines expressing fluorescent proteins targeted to the plastid stroma, plasma membrane, endoplasmic reticulum, tonoplast, nucleus, mitochondria, peroxisomes, F-actin and microtubules, we characterize the spatiotemporal relationships between the pavement cell chloroplasts (PCCs) and their subcellular environment. Observations on the PCCs suggest a source-sink relationship between the epidermal and the mesophyll layers, and experiments with the Arabidopsis mutants glabra2 (gl2) and immutans (im), which show altered epidermal plastid development, underscored their developmental plasticity. Our findings lay down the foundation for further investigations aimed at understanding the precise role and contributions of PCCs in plant interactions with the environment.


[The effect of estrogens in the etiopathogenesis of endometrial adenocarcinoma].
Recent data suggesting that oestrogens also encourage the onset of adenocarcinoma of the endometrium in man are reviewed. Emphasis is placed on the fact that this is most likely to occur when prolonged oestrogeni stimulation is not suitably opposed by progesterone. It is felt that the latter, or its synthetic homologues, should be employed in all long-standing cases of exogenous or endogenous hyperoestrogenism.


Oscillatory loading of a viscoelastic adhesive contact.
The cycle of loading and unloading of a spherically-tipped probe against an adhesive, viscoelastic plane specimen is studied by numerical integration of the relations between crack speed and apparent surface energy previously found for a linear 3-element viscoelastic solid with a Maugis-Dugdale law of force across the crack. It is found that even when the rate of loading is so slow that the loading and unloading curves almost coincide, suggesting purely elastic behaviour, the pull-off force can be appreciably greater than the elastic (JKR) value. When the normal force is modulated with a small amplitude sinusoidal variation during unloading--in order to find the contact stiffness--the contact radius barely changes, and the stiffness is close to that for a rigid flat punch instead of having the expected JKR value.


Treatment of articulatory dysfunction in Parkinson's disease using repetitive transcranial magnetic stimulation.
Neuroimaging has demonstrated that improved speech outcomes in Parkinson's Disease (PD) subsequent to behavioural treatment approaches are associated with increased activity in the motor and pre-motor cortex. High-frequency repetitive transcranial magnetic stimulation (rTMS) is capable of modulating cortical activity and has been reported to have significant benefit to general motor function in PD. It is possible that high-frequency rTMS may also have beneficial outcomes on speech production in PD. High-frequency (5 Hz) rTMS was applied to 10 active stimulation and 10 sham placebo patients for 10 min/day (3000 pulses), for 10 days and speech outcome measures and lingual kinematic parameters recorded at baseline and 1 week, 2 and 12 months post-stimulation. The findings demonstrated positive treatment-related changes observed in the active rTMS group when compared to the sham placebo control group at 2 and 12 months post-stimulation in speech intelligibility, communication efficiency ratio, maximum velocity of tongue movements and distance of tongue movements. The results support the use of high-frequency rTMS as a therapeutic tool for the treatment of articulatory dysfunction in PD.


Synthesis, Antiviral and Cytotoxic Activities of 2-(2-Phenyl carboxylic acid)-3-Phenylquinazolin -4(3H)-one Derivatives.
A series of novel 2,3-disubstitutedquinazolin-4(3H)-ones have been synthesized by condensation of 2-substituted benzo[1,3]oxazine-4-ones and anthranilic acid. Synthesized compounds were evaluated for in vitro antiviral activity against HIV, HSV and vaccinia viruses. 5-Bromo-2-(6-bromo-4-oxo-2-phenyl-4H-quinazolin-3-yl)-benzoic acid (MBR2) exhibited distinct antiviral activity against Herpes simplex and vaccinia viruses.


Dietary fibre fractions in cereal foods measured by a new integrated AOAC method.
The reliable determination of soluble, insoluble and total dietary fibre in baked goods and cereal flours is an important issue for research, nutritional labelling and marketing. We compared total dietary fibre (TDF) contents of selected cereal based foods determined by AOAC Method 991.43 and the new AOAC Method 2009.01. Fifteen bread and bakery products were included in the study. Our results showed that TDF values of cereal products determined by AOAC Method 2009.01 were always significantly higher than those determined by AOAC Method 991.43. This was explained by the inclusion of low molecular weight soluble fibre fractions and resistant starch fractions in the TDF measurement by AOAC 2009.01. This documents that nutritional labelling of cereal products poses the challenge how to update TDF data in nutrient databases in a reasonable time with an acceptable expenditure.


Even distribution of 133Xe bolus inhaled at residual volume in healthy subjects.
We selected from among 46 healthy students (22 to 31-yr-old) 7 subjects (group A) in whom the normalized height of phase IV (height of phase IV/phase IIIx100), after inhaling a bolus of He at RV, was very small (10%). We compared them with 6 subjects (group B) selected on the basis of a tall phase IV (78%, A vs. P P less than 0.005). Age and height were comparable, but weight was lower (P less than 0.05) and RV/TLC ratio (but not other spirographic indices) was larger (P less than 0.025) in group A. The average amplitude of cardiac oscillations was 4 times higher in group B (P less than 0.005). He closing volume, but not closing capacity was less in group A (P less than 0.05). A bolus of 133Xe inhaled at RV was nearly uniformly distributed in group A while producing a large vertical gradient in group B. The difference between groups A and B may reflect a difference in the mechanical properties of the chest wall leading to a less complete empting of the lung in the former group.


Antipredator vigilance in birds: modelling the 'edge' effect.
Many animals spend a large proportion of their time either foraging for food or watching out for predators (antipredator vigilance). There have been many theoretical and empirical studies investigating the trade-off between these two activities, especially in birds. Previous models of antipredator vigilance assume that all birds within the group spend the same amount of time feeding. However, many empirical studies have shown that individuals on the edge of flocks are more vigilant. Here we describe a vigilance model which investigates the effect of position on the birds' strategies by dividing the feeding area into an inner and outer region. The model examines how various parameters such as food availability and predation risk affect the strategies of individual birds according to whether they are in the inner or outer region. Our model predicts that birds in the outer group are always more vigilant than those in the inner region. Birds in the centre receive a higher payoff in each of the wide range of scenarios that we have considered, and so our model also indicates why dominant birds would choose to feed in the centre of the group; a prediction in accord with several empirical studies.


Breastfeeding experiences and perspectives on support among Chinese mothers separated from their hospitalized preterm infants: a qualitative study.
Chinese mothers of preterm infants often face obstacles to breastfeeding and commonly experience prolonged maternal-infant separation when their high-risk infants are hospitalized in a Neonatal Intensive Care Unit (NICU). This separation hinders mother-infant attachment and the establishment of breastfeeding. Currently, little is known about Chinese mothers' experiences breastfeeding their preterm infants, or their support needs. The aim of this study was to develop an understanding of mothers' experiences breastfeeding a hospitalized preterm infant and the support needed to establish a milk supply during the period separation from their infants. A qualitative descriptive study was conducted in Beijing in 2017. A total of 11 Chinese mothers were individually interviewed while separated from their infants. The interviews were audio-recorded and transcribed verbatim. A thematic analysis involving a seven-step protocol identified key themes. Mothers of preterm infants reported physically and mentally challenging breastfeeding experiences during the period they were separated from their babies. They viewed expressing breast milk as integral to their maternal role, even though some found expressing breastmilk exhausting. With little professional support available, the mothers depended upon nonprofessionals to establish breastfeeding. The study identified the difficulties mothers experienced establishing a milk supply while separated from their preterm infants, and the importance of access to health professional support.


Eating less the logical thing to do? Vulnerability to malnutrition with advancing age: A qualitative study.
The aim of this qualitative inquiry was to explore older New Zealanders perspectives and experiences of food and nutrition intake, to gain insights to factors that influence vulnerability to malnutrition risk at older age. Participants represented an ethnically diverse group of nutritionally vulnerable older adults (five malnourished and nine at risk), with most participants identifying as having an illness severity of moderate or severe. Thematic content analysis was performed using an integrated approach and took into account participants' nutritional status as determined using the Mini Nutritional Assessment-Short Form. Six key themes emerged. Almost all participants reported they had reduced their food intake and felt that eating less, was the 'logical' thing to do as they were now undertaking less physical activity. They described eating as a chore; they ate because they 'had to keep going', but hardly ever felt hungry (low appetite); they had lost interest in eating, and no longer found food fanciful. Being in the company of others encouraged eating except in stressful situations such as caring for an ill spouse. They had a preference for foods they had grown up with but could no longer readily access or needed to avoid some foods because of coexisting conditions or illnesses, food intolerance and chewing difficulties. Finally, participants tried to eat foods best for their health. The notion of healthy eating as consuming "more vegetables" was widely held, with some participants explaining this meant "less fat and less sugar". Overall, the low food intake reported by these participants appears shaped by a myriad of sociocultural and health related factors. The findings can be used as a foundation to develop strategies for preventing vulnerability to malnutrition with advancing age.


Prospective assessment of risk of bacteremia with colonoscopy and polypectomy.
A prospective assessment was made of the frequency of positive blood cultures in patients undergoing colonoscopy with or without polypectomy. A total of 270 patients underwent 280 colonoscopies, of these, there were 105 patients that had 111 polypectomies. Blood cultures were taken prior to and within 15 min following each procedure. Six of 280 (2.1%) preprocedural blood cultures were positive. Seven of 169 (4%) blood cultures were positive within 15 min of insertion of the colonoscope in the colonoscopy only group. Eight of 223 (3.6%) blood cultures were positive within 10 min of the polypectomy. There was no clinical evidence of sepsis during the 24 hr following these procedures. In order to determine appropriate postprocedural sampling intervals, we induced a Staphylococcus epidermidis bacteremia with a mean of 1.16 X 10(6) colony forming units/ml on 10 occasions in seven dogs. Within 30 min of inoculation, we were able to detect only one colony forming unit/ml. The rate of positive blood cultures during colonoscopy alone and following polypectomy during colonoscopy is comparable to other gastrointestinal endoscopy procedures. The most optimal time to collect blood cultures in order to detect transient bacteremia is as soon after the procedure as is feasibly possible.


Forskolin and phosphodiesterase inhibitors stimulate rat granulosa cell differentiation.
The effect of forskolin (an adenyl cyclase activator) and 1-methyl-3-isobutylxanthine (MIX, a phosphodiesterase inhibitor) on granulosa cell steroidogenesis and LH receptor formation was studied in vitro. Granulosa cells from immature hypophysectomized, estrogen-treated rats were cultured for 2-3 days in androstenedione-supplemented media in the absence or presence of FSH or forskolin (10(-7)-10(-4) M). Some cultures were also treated with forskolin with or without MIX (0.125-1.0 mM) or theophylline (1.25-10 mM). Forskolin (3 X 10(-6)-10(-4) M) stimulated the production of estrogen, progesterone, 20 alpha-hydroxypregn-4-en-3-one (20 alpha-OH-P) and cAMP in a dose-related manner to levels similar to or higher than that elicited by FSH alone. Similarly, forskolin and FSH both increased LH/hCG receptor content in cultured granulosa cells, although forskolin was only 50% as effective as FSH. Treatment with MIX alone increased basal levels of cAMP, accompanied by elevations of estrogen and progestin biosynthesis without affecting LH/hCG receptor content. In contrast, theophylline treatment only increased cAMP and progestin accumulation. Furthermore, MIX potentiated the stimulatory effects of forskolin and FSH on cAMP and progestin production. In contrast, MIX inhibited FSH- and forskolin-stimulated estrogen production. Thus, activation of adenyl cyclase and inhibition of cAMP breakdown in the cultured rat granulosa cells enhance steroidogenesis and LH receptor formation, reinforcing the concept that cAMP is a (but may not be the only) second messenger in the hormonal regulation of granulosa cell differentiation.


Malnutrition and pregnancy wastage in Zambia.
An analysis of recent nutritional status and dietary surveys in Zambia reveal a widespread prevalence of malnutrition. Pregnant women suffer from serious protein inadequacy. Variations in the nutritional status of the population is shown to vary with respect to different ecological conditions and to the level of socio-economic development within each province. Because of the interdependence between the nutritional health of the mother and the outcome of pregnancy, there is reason to believe that the prevailing malnutrition among pregnant women may be responsible, not only for lower birth weight and congenital malformations, but also, for increased maternal and perinatal mortality and morbidity in Zambia. Long-term solutions lie in the integration of nutrition concerns into sectoral development strategies; a commitment to reduce existing income disparities between the rural and urban areas; and innovative attempts to improve the efficiency of rural health institutions in the country.


Estimating total daily energy requirements in community-dwelling older adults: validity of previous predictive equations and modeling of a new approach.
Accurate estimation of energy requirements is crucial for health maintenance and prevention of malnutrition in older adults. This study aimed to assess the accuracy of predictive equations for estimating energy requirements in older adults and to test the validity of new predictive equations for this age group. This is a cross-sectional study including 38 Brazilian community-dwelling older adults aged 60-84 years, who had their total energy expenditure measured by doubly labeled water (TEEDLW). The energy expenditure was compared to the Institute of Medicine (Dietary Reference Intake (DRI)) and Vinken et al. previous predictive equations and three predictive models developed in a modeling sample. The agreement was assessed using intra-class correlation coefficient, Bland-Altman plots, and Lin's concordance correlation. Accuracy was evaluated considering ±10% of the ratio between estimated and measured energy expenditure. The mean (standard deviation) TEEDLW was 2656.7 (405.6) kcal/day for men and 2168.9 (376.9) for women. Vinken et al. and both DRI equations presented moderate to good degree of agreement, while the developed models vary from fair to very good agreement in comparison to DLW. The accuracy rate was the same for both DRI equations and Vinken et al. equation (60.53%). The new equations developed in this study had accuracy in predicting TEE for Brazilian older adults varying from 43.11% to 73.68%. The results corroborate the use of previous predictive equations for estimating energy requirements in Brazilian older adults. Further studies have the potential to explore the use of the developed models to assess energy needs in this population.


Spinal muscular atrophy: natural history and orthopaedic treatment of scoliosis.
To study the natural history of scoliosis in spinal muscular atrophy (SMA), 63 spinal radiographs of affected patients who attended the Muscle Clinic of Rizzoli Orthopaedic Institute between 1974 and 1988 were reviewed. All but one of the intermediate SMA patients, and all of the mild SMA patients who stopped walking had a scoliosis that ranged from 10 degrees to 165 degrees. Out of the 19 mild SMA patients still able to walk, 12 had a scoliosis ranging from 10 degrees to 45 degrees. Mean age at the onset of scoliosis was 4 years 4 months in intermediate SMA, and 9 years 10 months in mild SMA. Data on characteristics of the scoliotic curve are reported. The effectiveness of orthopaedic treatment in the prevention of scoliosis is discussed.


Pericentric inversion (Inv) 9 variant-reproductive risk factor or benign finding?
To report the unbalanced chromosome rearrangement rate and overall aneuploidy rate in day 5/6 embryos from a series of patients who underwent in vitro fertilization (IVF) with preimplantation genetic testing for structural rearrangements (PGT-SR) for the pericentric inversion 9 variant, inv(9)(p11q13) or inv(9)(p12q13), with concurrent 24 chromosome preimplantation genetic testing for aneuploidy (PGT-A). This was a retrospective cohort analysis. IVF cycles and embryo biopsies were performed by referring clinics. Fifty-two trophectoderm biopsy samples from seven couples were sent to a single lab for PGT-SR for an inversion 9 variant with concurrent 24 chromosome PGT-A using single-nucleotide polymorphism (SNP) microarrays with bioinformatics. The unbalanced rearrangement rate for this embryo cohort was 0/52 (0.0%); mean maternal age per embryo was 33.3 years (range 21-39 years). The overall euploid rate was 61.5% and aneuploidy rate was 38.5%. Chromosome 9 pericentric inversions did not result in unbalanced structural rearrangements in day 5/6 embryo samples, supporting that this population variant is not associated with increased reproductive risks.


Applying open-source software to laboratory data management.
The rise of new experimental techniques, such as high-throughput combinatorial methods, and the availability of large data sets by means of the Internet have greatly increased the amount of data that must be managed by relatively small projects. Scientific data management systems developed for large projects are often not available, suitable, nor affordable for projects with lesser resources. Increasing numbers of open-source frameworks have made available numerous options for smaller facilities to build for themselves effective and robust data management solutions. We will present considerations of these options and a case study.


Immunosuppressive 30-kDa protein in urine of pregnant women and patients with trophoblastic diseases.
Urine samples obtained from normal pregnant women and patients with trophoblastic diseases contain 30-kDa protein that suppresses phytohemagglutinin-induced T cell proliferation. The immunosuppressive protein was measured by a newly developed radioimmunoassay. The 30-kDa protein was demonstrated in almost all urine samples examined, fluid from hydatid vesicles and chorionic extracts, but not in any serum samples except at low levels in some sera from patients with choriocarcinoma. During pregnancy, the level of urinary 30-kDa protein was higher in the first (1625.5 +/- 1212.0 ng/ml, mean +/- S.D.) and second (1457.4 +/- 1332.4 ng/ml) trimesters than in the third trimester (460.6 +/- 419.0 ng/ml). The urinary 30-kDa protein/hCG ratios in patients with choriocarcinoma (8.3 +/- 10.9) were significantly higher than those in patients with hydatidiform mole (0.67 +/- 1.00, P < 0.01) and in all trimesters than those of normal pregnant women (0.54 +/- 0.44 in first trimester, P < 0.05; 0.63 +/- 0.46 in the second trimester, P < 0.05; 0.24 +/- 0.17 in the third trimester, P < 0.01). There is no significant difference between the ratios in hydatidiform mole and normal pregnancy. These findings and the fast disappearance of the 30-kDa protein from the circulation suggest that the 30-kDa protein plays a part in proliferation of trophoblastic cells in, or their invasion into the host by locally suppressing the immune reaction of the host and that the increase in the urinary 30-kDa protein level, in cases of choriocarcinoma, may be due to the malignant transformation of trophoblastic cells resulting in their rapid invasion.


[Arterial pressure responses to stretch and contraction of the gastrocnemius during stepwise interruption of its connections to the body].
In anesthetized cats, the pressoreaction of arterial pressure to stretch with weight of 3--4 kg and to contraction of the m. gastrocnemius due to direct 6--10--threshold electrical stimulation 50/sec, occurred due to reflex from the muscle receptors in 92--93%. 80--82% of the reaction was due to the afferents of the ischiatic nerve, and 11--12% to the afferents of vascular plexus. 7--8% were due to the blood outflow from the muscle and was unrelated to the stimulation.


Plasma nitrite as an indicator of cerebral ischemia during extracranial/intracranial bypass surgery in moyamoya patients.
Nitric oxide (NO) plays a key role in ischemia and shows potential as a biomarker for ischemia. We measured mixed venous nitrite (NO2-) as a proxy for NO, during controlled cerebral ischemia in patients with moyamoya disease (MMD) during direct extracranial/intracranial (EC/IC) bypass surgery with temporary occlusion of the M4 branch of the middle cerebral artery (MCA) to permit anastomosis with the superficial temporal artery (STA). This small, focal ischemic event is not reliably detected using cerebral oximetry, somatosensory evoked potentials (SSEPs) or electroencephalography (EEG). We enrolled nine adult MMD patients (n=8 female, n=1 male) undergoing direct EC/IC bypass surgery. Nitrite was measured at least one hour prior to MCA occlusion, and before, during and after anastomosis. Cortical function was monitored using either multi-lead EEG and SSEPs, or frontal EEG activity. Mixed venous NO2- was significantly elevated (p<0.05) within 12 min following arterial occlusion vs. baseline. An M4 branch of the MCA was cross clamped for a median duration of 18 (IQR = 5) minutes during anastomosis. One patient with elevated NO2- showed a transient neurologic deficit that resolved 3 days post-operatively. Mixed venous NO2- was significantly elevated shortly following cerebral artery occlusion vs. baseline in a majority of the study subjects, suggesting that NO2- is a potential biomarker for ischemia. Since all patients received identical burst suppression anesthesia and vasopressors, the fact that NO2- was not elevated during cross-clamp in all patients supports the conclusion that the NO2- elevation is likely due to ischemia.


Five Japanese cases of antidesmoglein 1 antibody-positive and antidesmoglein 3 antibody-negative pemphigus with oral lesions.
Oral mucosal lesions develop in pemphigus vulgaris, but not in pemphigus foliaceus. This clinical phenomenon is explained by the 'desmoglein (Dsg) compensation theory'. Dsg3 and Dsg1 are major autoantigens for pemphigus vulgaris and pemphigus foliaceus, respectively. Dsg3 is overexpressed and Dsg1 is weakly expressed on the oral mucosa. Thus, on the oral mucosa, suppression of Dsg3 function by anti-Dsg3 autoantibodies is not compensated by weakly expressed Dsg1 in pemphigus vulgaris, while suppression of Dsg1 function by anti-Dsg1 autoantibodies is perfectly compensated by richly expressed Dsg3 in pemphigus foliaceus. We present five Japanese patients with pemphigus who deviate from this theory, i.e. all patients showed oral lesions (three also had cutaneous lesions) and reacted only with Dsg1, but not with Dsg3, by enzyme-linked immunosorbent assay. To confirm whether the unique clinical phenotypes in our patients were due to a different immunological profile from that in classical pemphigus, we examined the reactivity of the patient sera by immunoprecipitation-immunoblotting analysis using five Dsg1/Dsg2 domain-swapped molecules. The sera of two patients who had only oral lesions tended to react with the extracellular (EC) 5 domain of Dsg1, the domain that is considered nonpathogenic in classical pemphigus foliaceus. Sera of three patients with mucocutaneous lesions reacted with EC1 domain or with both EC1 and EC2 domains of Dsg1, like classical pemphigus foliaceus. These results indicate that antigenic diversity of anti-Dsg1 antibodies in these patients may cause the unique oral mucosal and cutaneous lesions, although further studies are required to elucidate the pathomechanisms.


Repeatability of refraction and corrected visual acuity in keratoconus. The CLEK Study Group. Collaborative Longitudinal Evaluation of Keratoconus.
The purpose of the test-retest phase of the Collaborative Longitudinal Evaluation of Keratoconus (CLEK) Study was to determine the repeatability of the various parts of the CLEK Study protocol. This paper presents the test-retest parameters of the refraction protocol. We examined 138 CLEK Study-eligible patients on two occasions (median, 90 days; range, 22 to 268 days). All patients underwent subjective refraction on two occasions, and contact lens over-refractions were performed either over the patient's habitual rigid contact lenses or over a trial rigid contact lens equal in base curve to the steep keratometric reading in nonrigid contact lens wearers. Mean interoccasion differences +/- SD were -0.32 +/- 2.91 D and -0.17 +/- 1.39 D for subjective refraction sphere and cylinder power, respectively, and the mean absolute difference for subjective refraction cylinder axis was 18.1 +/- 20.2 degrees. The mean interoccasion difference +/- SD for high-contrast visual acuity with subjective refraction was 0.38 +/- 10.9 letters correct. Mean interoccasion differences +/- SD were -0.11 +/- 0.81 D and 0.02 +/- 0.67 D for contact lens over-refraction sphere and cylinder power, respectively, and the mean absolute difference for contact lens over-refraction cylinder axis was 11.6 +/- 9.9 degrees. The mean interoccasion difference +/- SD for visual acuity with contact lens over-refraction was 0.50 +/- 5.2 letters correct and 0.71 +/- 6.9 letters correct for high- and low-contrast visual acuity, respectively. The repeatability of subjective refraction in keratoconus patients is good but somewhat lower than that found in nondiseased eyes. Only 36% of our repeat measures of sphere power from subjective refraction fell within 0.50 D of each other, compared with more than 90% in studies of normal eyes.


The effect of selected immunostimulants on hemocytes of the false black widow Steatoda grossa (Theridiidae) spiders under chronic exposition to cadmium.
The aim of this study was to analyze whether, and to what extent, long-term exposure to cadmium, administered in sublethal concentrations by the oral route, caused changes in the immune potential of hemocytes in adult female Steatoda grossa spiders. We used artificial and natural immunostimulants, namely phorbol 12-myristate 13-acetate (PMA) and bacterial cell suspension based on Gram-positive (G+, Staphylococcus aureus) and Gram-negative (G-, Pseudomonas fluorescens) bacteria, to compare the status of hemocytes in nonstimulated individuals and those subjected to immunostimulation. After cadmium exposure, the percentage of small nongranular hemocytes in response to G+ cell suspension and PMA mitogen was decreased. Furthermore, in the cadmium-intoxicated spiders the percentage of plasmatocytes after immunostimulation remained lower compared to the complementary control group. Exposure to cadmium also induced several degenerative changes, including typical apoptotic and necrotic changes, in the analyzed types of cells. Immunostimulation by PMA mitogen and G+ bacterial suspension resulted in an increase in the number of cisterns in the rough endoplasmic reticulum of granulocytes, in both the control group and cadmium-treated individuals. These changes were accompanied with a low level of metallothioneins in hemolymph. Chronic cadmium exposure may significantly weaken the immune defense system of spiders during infections.


Nanomedicine Strategies for Targeting Tumor Stroma.
The tumor stroma, or the microenvironment surrounding solid tumors, can significantly impact the effectiveness of cancer therapies. The tumor microenvironment is characterized by high interstitial pressure, a consequence of leaky vasculature, and dense stroma created by excessive deposition of various macromolecules such as collagen, fibronectin, and hyaluronic acid (HA). In addition, non-cancerous cells such as cancer-associated fibroblasts (CAFs) and the extracellular matrix (ECM) itself can promote tumor growth. In recent years, there has been increased interest in combining standard cancer treatments with stromal-targeting strategies or stromal modulators to improve therapeutic outcomes. Furthermore, the use of nanomedicine, which can improve the delivery and retention of drugs in the tumor, has been proposed to target the stroma. This review focuses on how different stromal components contribute to tumor progression and impede chemotherapeutic delivery. Additionally, this review highlights recent advancements in nanomedicine-based stromal modulation and discusses potential future directions for developing more effective stroma-targeted cancer therapies.


Quality of life among Syrian patients with war-related lower limb amputation at the Military Hospital in Lattakia.
To describe the quality of life(QOL) of Syrian people with lower limb amputation after the war. A cross-sectional study conducted at the Military Hospital in Lattakia, from May to August 2019. A convenience sample of 65 adult males who had previously undergone amputation of a lower limb was included in this study. Participants' data were collected including age, marital status, employment, time since amputation, level of amputation, type of amputation and the use of assistive devices. The QOL was measured using the World Health Organization Quality of Life Brief Version (WHO QOL-BREF). Data analysis was done by using SPSS version 20. Forty (61.5%) of subjects were between age of 40-60. Below knee and unilateral lower-limb amputees formed the highest number 52 (80.0%) and 51 (78.5%) respectively. The mean scores of environment, physical health, psychological, and social relationships domains of QOL were 15.86, 15.18, 14.66, and 6.64, respectively. There were statistically significant differences in various domains of QOL between groups with different status of employment, financial support, amputated lower limb, duration since amputation, and cause of amputation (P < 0.05). There is a need to pay attention to experiences and the quality of life among Syrian patients with war-related amputation.


High sensitivity and specificity in proposed clinical diagnostic criteria for anti-N-methyl-D-aspartate receptor encephalitis.
To determine the validity of the proposed clinical diagnostic criteria for anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis in paediatric patients. The diagnostic criteria for anti-NMDAR encephalitis proposed by Graus et al. (2016) use clinical features and conventional investigations to facilitate early immunotherapy before antibody status is available. The criteria are satisfied if patients develop four out of six symptom groups within 3 months, together with at least one abnormal investigation (electroencephalography/cerebrospinal fluid) and reasonable exclusion of other disorders. We evaluated the validity of the criteria using a retrospective cohort of paediatric patients with encephalitis. Twenty-nine patients with anti-NMDAR encephalitis and 74 comparison children with encephalitis were included. As expected, the percentage of patients with anti-NMDAR encephalitis who fulfilled the clinical criteria increased over time. During the hospital inpatient admission, most patients (26/29, 90%) with anti-NMDAR encephalitis fulfilled the criteria, significantly more than the comparison group (3/74, 4%) (p<0.001). The median time of fulfilling the criteria in patients with anti-NMDAR encephalitis was 2 weeks from first symptom onset (range 1-6). The sensitivity of the criteria was 90% (95% confidence interval 73-98) and the specificity was 96% (95% confidence interval 89-99). The proposed diagnostic criteria for anti-NMDAR encephalitis have good sensitivity and specificity. Incomplete criteria do not exclude the diagnosis. The proposed clinical diagnostic criteria for anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis by Graus et al. (2016) have high sensitivity and specificity in paediatric patients. The median time of fulfilling the criteria in patients with anti-NMDAR was 2 weeks from first symptom onset.


A chromia-based sorbent for the enrichment of phosphotyrosine.
Developing of new core@shell particles (CSPs) bearing metal oxides on their outer surfaces is of a great interest. Such hybrid systems have many benefits, i.e., low cost, operation simplicity, chemical stability and tunability along with simple recoverability and reusability that make them suitable as dispersive solid phase extraction (DSPE) sorbents for selecting/extracting different types of molecular structures. Accordingly, herein, novel chromia-based CSPs were successfully prepared and utilized as efficient DSPE for selective enrichment toward phosphotyrosine (pTyr). A modified version of Stöber method was used to prepare highly dispersed core particles that were further coated with the chromium oxide. The outer shell surface morphology and thickness of SiO2@Cr2O3-CSP system were characterized by scanning electron microscopy (SEM) and transmission electron microscopy (TEM), whereas the surface functionalities were determined using X-ray photoelectron spectroscopy (XPS), FT-IR spectroscopy and zeta potential. The prepared chromia sorbent showed a significant improvement in extracting a probe-analyte (pTyr) compared to the results obtained by titania-based counterparts. As well to this, a noticeable stability of the SiO2@Cr2O3-CSP sorbent was remarkably achieved which upon simple solvent-wash cycles, the studied sorbent can be regenerated/reused. Noticeably low-levels of LOD and LOQ (3.0 and 15 pg mL-1) were attained with good linearity (R2 of 0.9995), batch-to-batch reproducibility (RSD% ≤ 10) and run-to-run repeatability (RSD% ≤ 5.5).


Noninvasive Detection of Extracellular pH in Human Benign and Malignant Liver Tumors Using CEST MRI.
In this study, we aimed to use 3T magnetic resonance imaging (MRI), which is clinically available, to determine the extracellular pH (pHe) of liver tumors and prospectively evaluate the ability of chemical exchange saturation transfer (CEST) MRI to distinguish between benign and malignant liver tumors. Different radiofrequency irradiation schemes were assessed for ioversol-based pH measurements at 3T. CEST effects were quantified in vitro using the asymmetric magnetization transfer ratio (MTRasym) at 4.3 ppm from the corrected Z spectrum. Generalized ratiometric analysis was conducted by rationing resolved ioversol CEST effects at 4.3 ppm at a flip angle of 60 and 350°. Fifteen patients recently diagnosed with hepatic carcinoma and five patients diagnosed with hepatic hemangioma [1 male; mean age, 48.6 (range, 37-59) years] were assessed. By conducting dual-power CEST MRI, the pH of solutions was determined to be 6.0-7.2 at 3T in vitro. In vivo, ioversol signal intensities in the tumor region showed that the extracellular pH in hepatic carcinoma was acidic(mean ± standard deviation, 6.66 ± 0.19), whereas the extracellular pH was more physiologically neutral in hemangioma (mean ± standard deviation, 7.34 ± 0.09).The lesion size was similar between CEST pH MRI and T2-weighted imaging. dual-power CEST MRI can detect extracellular pH in human liver tumors and can provide molecular-level diagnostic tools for differentiating benign and malignant liver tumors at 3T.


Effect of temperature on post-wintering development and total lipid content of alfalfa leafcutting bees.
Temperature plays an important role in effective management of the alfalfa leafcutting bee [Megachile rotundata (F.); Megachilidae], the major commercial pollinator of seed alfalfa [Medicago sativa (L.); Fabaceae] in North America. To improve our understanding of threshold and optimum rearing temperatures of M. rotundata, we examined the effect of temperature on postwintering development by using a greater number of temperature treatments than applied in previous studies (19 versus eight or fewer) and analytical tools formulated to model nonlinear relationships between temperature and insect development rates. We also tested the hypothesis that rearing temperature influences adult body lipid content at emergence, which could affect adult survival, establishment and performance as a pollinator, and reproductive success. We found that the Lactin-2 and Briere-2 models provided the best fits to data and gave reasonable estimates of lower (16-18°C) and upper (36-39°C) developmental thresholds and optimum (33-34°C) rearing temperatures for maximizing development rate. Bees successfully emerged over a broad range of temperatures (22-35°C), but variation in development rate among individuals reared at the same temperature was lowest at 31-33°C. The optimum rearing temperature to maximize the proportion of body lipids in adults was 27-29°C. Our results are discussed in relation to previous findings and speak to the difficulties in designing practical rearing guidelines that simultaneously maximize development rate, survival, and adult condition, while synchronizing adult emergence with alfalfa bloom.


In vitro binding of the very potent and selective D-2 dopamine agonist, [3H]N-0437 to calf caudate membranes.
N-0437, a non-catecholic aminotetralin has recently been described as a very potent and selective dopamine D-2 agonist. In this study the in vitro binding of [3H]N-0437 (specific activity 80.6 Ci/mmol) to calf caudate membranes is described. It was found that [3H]N-0437 binds with a high affinity (KD = 0.17 nM) and a low proportion of non-specific binding. Moreover the binding was saturable with a high number of binding sites (Bmax = 703 +/- 28 fmol/mg protein) and reversible (dissociation half-time = 68 min). Pharmacological analysis of [3H]N-0437 binding showed that it was selective for dopamine receptors and that it was also stereoselective for D-2 receptors. Non-dopaminergic drugs were without exception very poor displacers. Taken together the results suggest that [3H]N-0437 labels dopamine D-2 receptors with a high selectivity in the calf brain, and thus, that it should be a useful tool in studies of central dopamine receptors.


The black-white suicide paradox: possible effects of misclassification.
This research addresses the paradox that the crude and age-adjusted suicide rates of United States blacks are less than half those of whites despite similar risks. Upper and lower limits for true suicide rates are estimated to assess the potential for differential suicide misclassification by race. Construction of these two rate scenarios respectively incorporate one or all of the three cause-of-death categories identified in the literature as most prone to obscure suicides: injury of undetermined intent and unintentional poisonings and drownings. The data source is the US Centers for Disease Control and Prevention's Web-based Injury Statistics Query and Reporting System, and the observation period is 1999-2002. We found that as in the official rates, the racial suicide gap persists within the lower and upper limit scenarios. However, there is marked shrinkage under the upper limit scenario. That scenario even generates rate crossovers for males ages 45-54 years and females ages 85 years and older. Suicide data appear relatively more deficient for black females than for black males. Racial data disparities are minimal for youth and young adults, and maximal for middle-aged males and the oldest and younger middle-aged females. Results strongly indicate greater susceptibility of medico-legal authorities to misclassify black suicides than white suicides. To demystify the racial suicide paradox, research is needed on medical histories and other biographical information that are accessible by the authorities in equivocal cases. To meet the standards of evidence-based medicine and public health, high-quality suicide data are an imperative for risk group delineation; risk factor identification; policy formulation; program planning, implementation, and evaluation; and ultimately, effective prevention.


The chloroplast trnT-trnF region in the seed plant lineage Gnetales.
The trnT-trnF region is located in the large single-copy region of the chloroplast genome. It consists of the trnL intron, a group I intron, and the trnT-trnL and trnL-trnF intergenic spacers. We analyzed the evolution of the region in the three genera of the gymnosperm lineage Gnetales (Gnetum, Welwitschia, and Ephedra), with especially dense sampling in Gnetum for which we sequenced 41 accessions, representing most of the 25-35 species. The trnL intron has a conserved secondary structure and contains elements that are homologous across land plants, while the spacers are so variable in length and composition that homology cannot be found even among the three genera. Palindromic sequences that form hairpin structures were detected in the trnL-trnF spacer, but neither spacer contained promoter elements for the tRNA genes. The absence of promoters, presence of hairpin structures in the trnL-trnF spacer, and high sequence variation in both spacers together suggest that trnT and trnF are independently transcribed. Our model for the expression and processing of the genes tRNA(Thr)(UGU), tRNA(Leu)(UAA), and tRNA(Phe) (GAA) therefore attributes the seemingly neutral evolution of the two spacers to their escape from functional constraints.


Lighting pattern and photoperiod affect the range use and feather cover of native laying hens under free range condition.
The study aimed to investigate the effects of lighting pattern and photoperiod on range use, feather cover and gait score of native laying hens. Six hundred and thirty 19-wks-old Beijing You Chicken (BYC) pullets were randomly allocated to 6 groups with 105 birds each, 3 replicates per group, reared in individually lit indoor pens with separate covered shed and outdoor areas. A 2 × 3 factorial experiment (2 lighting patterns: continuous and intermittent lighting; 3 photoperiods: 16 h, 14 h, 12 h) was arranged indoors, including 16L:8D (6:00-22:00) for group 1; 12L:2D:4L:6D (6:00-18:00,20:00-24:00) for group 2; 14L:10D (6:00-20:00) for group 3; 10L:2D:4L:8D (6:00-16:00,18:00-22:00) for group 4; 12L:12D (6:00-18:00) for group 5, and 8L:4D:4L:8D (6:00-14:00,18:00-22:00) for group 6, respectively. The number of hens in indoor pen, covered shed and outdoor area were counted at 8:00, 9:00, 10:00, 11:00, 12:00, 13:00, 14:00 for consecutive 3 sunny days at 34 wks and 36 wks of age, feather cover and gait score of the laying hens were assessed at the end of 36 wks. The results showed that daily average hen percentage was the highest in continuous 12 h group (63.67%), and the lowest in intermittent 14 h group (58.36%) in indoor pen (P < 0.05); the daily average hen percentage was the lowest in continuous 12 h group (16.05%), and the highest in intermittent 14h group (21.22%) in outdoor area (P < 0.05). Lighting pattern significantly affected hen percentage in indoor pen and outdoor area, the hen percentage in indoor pen was higher in continuous lighting groups than in intermittent lighting groups (62.09% vs. 59.23%) (P < 0.05), the hen percentage in outdoor area was lower in continuous lighting groups than in intermittent lighting groups (16.60% vs. 19.95%) (P < 0.05). Photoperiod had no effect on the hen percentage (P > 0.05), but time of day affected the hen percentage in different areas (P < 0.05). The feather cover score was higher in intermittent lighting groups than in continuous lighting groups (17.43 vs. 15.04, P < 0.05). The average hen percentage in indoor pen is strongly negatively correlated with the feather cover score (r = -0.880, P = 0.050), and the hen percentage in outdoor area is strongly positively correlated with the feather cover score in intermittent lighting condition (r = 0.811, P < 0.05). The present study suggested that more range use is beneficial for the feather cover and physical health of laying hens under free range condition, and intermittent lighting is more conducive to range use and feather cover of native laying hens, which may be related to its affecting hens' rhythmic activities, increasing adaptation to outdoor environment, and reducing the incidence of feather pecking and parasites.


[A patient-expert in patient education. The story of practice].
The notion of patient-expert has existed in France since the years 2000 and has been used by patients' associations, notably the Association François Aupetit (AFA). Patrick Helle, who suffers from a chronic inflammatory disease, holds a degree in therapeutic education. He organizes and hosts workshops on this topic, alone or in cooperation with healthcare professionals at three public hospitals. This patient-expert serves as a bridge between caregivers and patients, sharing his experience as a patient and transmitting experiential knowledge. He shares his story with us.


High resolution bright field electron microscopy of biological specimens.
Various parameters which affect the information content in bright field electron micrographs of biological specimens is discussed. Special attention is paid to the resolution of phase contrast imaging, specimen supports and radiation damage.


Streptococcus dentisani is a common inhabitant of the oral microbiota worldwide and is found at higher levels in caries-free individuals.
Streptococcus dentisani has been proposed as a promising probiotic against tooth decay, due to its ability to buffer acidic pH and to inhibit the growth of oral pathogens. However, it is unknown if this bacterial species has a global distribution. The current study aimed to establish the presence of S. dentisani in oral samples from different geographic locations by identifying the sequence of its 16S rRNA gene in available datasets from across the globe. In addition, an analytical and cross-sectional study was carried out to determine if the levels of this probiotic strain are higher in caries-free individuals compared to those with dental caries. Samples from various geographical sources demonstrated that S. dentisani is present in saliva and dental plaque from individuals of different continents. Typical S. dentisani levels in saliva ranged from 104 to 105 cells/ml and a total of 106-107 cells in dental plaque. Using real-time qPCR, S. dentisani was quantified from supragingival dental plaque of 25 caries-free and 29 caries-active individuals from a Mexican children population, where significantly higher proportions of S. dentisani were found in the caries-free group (p = 0.002). Finally, a negative correlation was found between caries levels (as measured by the dmft caries index) and the percentage of S. dentisani (p < 0.001). Thus, the current manuscript indicates that this species has a global distribution, can be found in saliva and dental plaque, and appears to be present in higher numbers in plaque samples from caries-free children.


Expression of basic fibroblast growth factor isoforms in postmitotic sympathetic neurons: synthesis, intracellular localization and involvement in karyokinesis.
Low and high molecular weight isoforms of the mitogen and multifunctional cytokine basic fibroblast growth factor (FGF-2) are up-regulated in neurons and glial cells in response to peripheral nerve lesion. While synthesis, regulation and functions of FGF-2 in non-neuronal cells are well established, the significance of neuronal FGF-2 remains to be investigated in the peripheral nervous system. Therefore, the expression, intracellular localization and possible effects of FGF-2 isoforms were analyzed in primary sympathetic neurons derived from the rat superior cervical ganglion. FGF-2 is detected in the nucleus and in perinuclear Golgi fields of early postnatal neurons which also express mRNA and protein for the FGF receptor type 1. Biolistic transfection of plasmids encoding FGF-2 isoforms fused to fluorescent proteins demonstrates nuclear targeting of 18 kDa FGF-2 and 23 kDa FGF-2 with prominent accumulation in the nucleolus of neurons. Neither overexpression nor treatment with FGF-2 isoforms promotes survival of sympathetic neurons deprived of nerve growth factor; however, neuronal transfection of the high molecular weight FGF-2 isoform in dissociated and slice cultures results in a bi- or multinuclear phenotype. The present study provides evidence for neuronal synthesis and targeting of FGF-2 to the nucleus and Golgi apparatus supporting a dual role of FGF-2 in the nucleus and secretory pathway of sympathetic neurons.


Immunological studies of hsv-infection of resistant and susceptible inbred strains of mice.
DBA/2 mice were found to be quite susceptible to infection with herpes simplex virus (HSV) while C57BL/6 mice and F1 hybrids between the 2 strains were relatively resistant. This difference was most marked after ip infection, but could also be demonstrated after intracerebral, intravenous or subcutaneous infection. In both strains the LD50 was considerably higher after ip infection than after iv infection, and a dose of X-irradiation was required to kill the mice by sc infection. A/J and BALB/c mice were equally susceptible after ip infection but differed significantly after iv infection. C57BL/6 were made susceptible to ip infection by immunosuppression with antilymphocyte serum or cyclophosphamide. LPS, when given simultaneously with HSV also markedly increased the susceptibility of C57BL/6 mice. Susceptible DBA/2 mice which surrvived a low dose of HSV ip were not immune but C57BL/6 mice surviving a high dose were immune against rechallenge. Both strains of mice could be protected by an apathogenic, tissue-culture-attenuated strain of HSV against infection with the virulent strain. They could also be protected by iv injection of a sublethal dose against a lethal ip infection.


A loading-dose infusion scheme for intravenous tocolysis with ritodrine: a pilot study.
A loading-dose infusion scheme for intravenous ritodrine therapy was tested in twelve patients with preterm labour. We started with a rather high (386 micrograms/min) infusion rate, but the moment tocolysis was reached this infusion rate was reduced to a level needed to maintain the plasma concentration then found. Plasma samples of ritodrine were taken the moment tocolysis was reached and in the steady state, and compared with each other and with expected and calculated plasma concentrations. In the dynamic loading phase we found a half-life for ritodrine of 1 h. This half-life of 1 h can be explained by cumulation of ritodrine in the central compartment and is therefore called cumulation t1/2. In developing an infusion scheme with a loading dose for ritodrine, this cumulation t1/2 of 1 h should be taken into account.


Risk of peri-operative complications in children receiving preoperative steroids.
Steroid use predisposes adult patients to increased perioperative complications including wound dehiscence and delayed wound healing. A similar large study investigating the perioperative impact of steroid use in pediatric patients has not been performed. The National Surgical Quality Improvement Project Pediatric Database was queried from 2012-2017 to identify patients who received steroid preoperatively. Patient demographics, comorbidities, surgical variables, and outcomes were compared between cohorts. Patients were propensity score matched and thirty-day adverse events were compared. Of 425,251 pediatric surgery patients, 9716 (2.3%) received preoperative steroids. Pediatric patients treated with steroids were older and had more comorbidities. After propensity score matching, the steroid population had a significantly higher rate of adverse events, including prolonged hospital stay (15.3% vs. 9.1%, p < 0.001), seizure (0.9% vs. 0.4%, p < 0.001), readmission (14.4% vs. 9.2%, p < 0.001), and death (2.2% vs. 1.1%, p < 0.001). Preoperative steroid use is independently associated with increased 30-day postoperative adverse events among pediatric patients. Given the significant impact of steroid use on surgical outcomes, the risks and benefits of steroid treatment in children receiving surgery should be carefully evaluated.


The mdm2 proto-oncogene sensitizes human medullary thyroid carcinoma cells to ionizing radiation.
We have analysed the radiation response of a human medullary thyroid carcinoma cell line (MTT), characterized by the absence of a functional p53 protein, and the consequences of MDM2 overexpression in this process. We show that the product of the mdm2 proto-oncogene is able to sensitize MTT cells to ionizing radiation. After radiation treatment, MTT cells display histograms consistent with a G2M arrest. MTT cells expressing MDM2 (MTT-mdm2) are unable to respond to DNA damage with G2M arrest, and display a high percentage of apoptosis. MTT-mdm2 cells show high levels of E2F-1 protein, suggesting that the induction of apoptosis observed upon MDM2 overexpression could be dependent on E2F-1. This observation is further supported with assays showing that E2F-1 binding to specific DNA sequences is enhanced in MTT-mdm2 cells. Likewise, transactivation of reporter constructs exclusively dependent on E2F-1 is also elevated after transfection with MDM2. This effect can be reverted by transient transfection with p19ARF. To link the expression of E2F-1 with the induction of apoptosis, we generated clonal cell lines overexpressing E2F-1. Transfection with E2F-1 results in a low number of outgrowing colonies with reduced proliferation rates, indicating that E2F-1 is deleterious for cell growth. This negative regulation correlates with an increase in the percentage of the cell population with DNA content below 2N, suggesting that E2F-1 promotes apoptosis. Finally, overexpression of E2F-1 sensitizes MTT cells to radiation exposure. We conclude that the effects observed by MDM2 overexpression could be mediated by E2F-1.


[Determination of antituberculous antibodies in the cerebrospinal fluid by an immunoenzyme assay method in patients with tuberculous meningitis].
Possibilities of using enzyme immunoassay to identify specific antibodies to M. tuberculosis in the cerebrospinal fluid of 44 patients with tuberculous meningitis and 81 cases with other diseases of the central nervous system were analysed. The assay sensitivity and specificity in an active period of tuberculous meningitis made up 100 and 97.5%, respectively. The findings permit one to recommend the enzyme immunoassay for an early diagnosis of tuberculous meningitis.


Directed evolution of a neutrophilic and mesophilic methanol dehydrogenase based on high-throughput and accurate measurement of formaldehyde.
Methanol is a promising one-carbon feedstock for biomanufacturing, which can be sustainably produced from carbon dioxide and natural gas. However, the efficiency of methanol bioconversion is limited by the poor catalytic properties of nicotinamide adenine dinucleotide (NAD+)-dependent methanol dehydrogenase (Mdh) that oxidizes methanol to formaldehyde. Herein, the neutrophilic and mesophilic NAD+-dependent Mdh from Bacillus stearothermophilus DSM 2334 (MdhBs) was subjected to directed evolution for enhancing the catalytic activity. The combination of formaldehyde biosensor and Nash assay allowed high-throughput and accurate measurement of formaldehyde and facilitated efficient selection of desired variants. MdhBs variants with up to 6.5-fold higher Kcat/KM value for methanol were screened from random mutation libraries. The T153 residue that is spatially proximal to the substrate binding pocket has significant influence on enzyme activity. The beneficial T153P mutation changes the interaction network of this residue and breaks the α-helix important for substrate binding into two short α-helices. Reconstructing the interaction network of T153 with surrounding residues may represent a promising strategy to further improve MdhBs, and this study provides an efficient strategy for directed evolution of Mdh.


Novel yolk-shell structure bismuth-rich bismuth molybdate microspheres for enhanced visible light photocatalysis.
The yolk-shell structure Bi(4-2x)Mo(x)O6 (x⩽1) microspheres were successfully synthesized via a simple solvothermal method. The morphology, structure and photocatalytic performances of the samples in the degradation of rhodamine B (RhB) and methyl orange (MO) were characterized by X-ray photoelectron spectroscopy, scanning electron microscopy, transmission electron microscopy, X-ray diffraction, UV-vis absorption spectroscopy and electrochemical impedance spectra, respectively. The results show that the yolk-shell structure Bi(2.38)Mo(0.81)O6 microspheres exhibit the best photocatalytic performance for the degradation of RhB and MO with a degradation rate of 99% and 72% under visible light irradiation.


Diffusion ordered NMR spectroscopy measurements as screening method of potential reactions of API and excipients in drug formulations.
In the development of new pharmaceutical formulations it is important to consider the possible interactions between the active pharmaceutical ingredient (API) and excipients which is a well-known problem. The objective of the work presented here was to investigate such reactions by means of diffusion ordered NMR spectroscopy (DOSY). The known reaction of 5-aminosalicylic acid (5-ASA) and the excipient citric acid was studied. Three reaction products have been verified by DOSY, 1H NMR and HPLC measurements. Despite a poor separation in the DOSY diagram, the reaction products could be assign due to the processing of thoughtful selected parts of the signals. The reaction of 5-ASA with formic acid and benzocaine with dibutyl phthalate was also studied by means of DOSY experiments.


Acinar cell carcinoma arising in the stomach: a case report with literature review.
Acinar cell carcinomas (ACCs) are uncommon malignant tumors of the exocrine pancreas, constituting 1% to 2% of all nonendocrine pancreatic neoplasms. Cases of acinar cell carcinoma developing in heterotopic pancreatic tissue are extremely rare. To the best of our knowledge, no cases of primary ACC developing in the stomach have been reported in the literature. We report the first case of a primary ACC arising in the stomach in an 86-year-old female who presented with a 5-cm gastric submucosal mass with superficial ulceration and a history of anemia. The neoplasm exhibited typical acinar morphology. Immunohistochemical studies demonstrated strong positive reactivity for antitrypsin and antichymotrypsin, and electron microscopy confirmed the presence of zymogen granules. A complete metastatic workup failed to identify any primary pancreatic tumor or other nonpancreatic tumor.


Restoring malaligned implants: clinical and technical perspectives.
Despite careful attention, implants occasionally are placed at less than ideal angles. A combination of techniques can be implemented in the laboratory to correct malalignment. The "thread-timed impression" technique to assist with these restorations is described.


PARP inhibitors: polypharmacology versus selective inhibition.
Inhibition of ADP-ribosyltransferases with diphtheria toxin homology (ARTD), widely known as the poly(ADP-ribose) polymerase (PARP) family, is a strategy under development for treatment of various conditions, including cancers and ischemia. Here, we give a brief summary of ARTD enzyme functions and the implications for their potential as therapeutic targets. We present an overview of the PARP inhibitors that have been used in clinical trials. Finally, we summarize recent insights from structural biology, and discuss the molecular aspects of PARP inhibitors in terms of broad-range versus selective inhibition of ARTD family enzymes.


Simple and Conditional Discrimination and Specific Reinforcement in Teaching Reading: An Intervention Package.
This study evaluated an intervention package combining simple and conditional discrimination training and specific reinforcement for each stimulus class in teaching reading of simple words to individuals with intellectual disabilities. In conditional discrimination training, participants matched printed words and pictures to the recorded sounds made by the pictured objects and animals. Fourteen children and adolescents with intellectual disabilities were assigned to an experimental and a control group. The two groups' performance did not differ in the pretest. The experimental group demonstrated equivalence class formation and read the words that participated in the equivalence classes, whereas the control group did not.


Control of vasopressin secretion in the newborn lamb.
The plasma sodium, osmolality, and arginine vasopressin (AVP) responses to phlebotomy, hypertonic saline, water loading and fluid restriction were studied in 2--49 day old lambs. Phlebotomy of 10 and 20% of the lamb's estimated blood volume produced 37- and 44-fold increments in plasma AVP, without a concomitant change in plasma sodium or osmolality. The infusion of 10 mEq/kg sodium chloride produced a 12% rise in plasma sodium concentration accompanied by a 7-fold rise in plasma AVP. Water loading with 100 ml/kg hypotonic fluid produced a significant fall in plasma sodium concentration (10.7%) and a decrease in plasma AVP. Eighteen hr of water deprivation evoked a 7-fold increase in AVP. These results indicate that the newborn lamb is capable of responding appropriately to known stimuli for AVP secretion. The stimulus response ratio (SRR): (formula: see text) of newborn lambs was nearly identical after hypertonic saline and water loading and was also quite similar to that of the adult ewe after a saline challenge. The SRR of water deprived lambs was greater than that after the other stimuli, presumably reflecting combined volume and osmolar stimuli. We conclude that the neurohypophysis and the volume receptor systems of the newborn lamb are capable of appropriate, mature AVP responsiveness during the first days of extrauterine life.


A common idiotope on human rheumatoid factors identified by a hybridoma antibody.
Human monoclonal and polyclonal anti-IgG autoantibodies [rheumatoid factors (RFs)] are composed primarily of kappa light chains, and may display cross-reactive idiotypes. However, the nature of the shared idiotope(s) has remained unclear. We have prepared a murine hybridoma antibody (17-109) that recognizes an idiotope present on 30% (3/10) of human IgM-RF paraproteins, and absent on immunoglobulins without RF activity. The idiotope was measurable on isolated, intact kappa light chains, but not on light-chain tryptic peptides, nor on isolated heavy chains. A comparison of the binding to 17-109 of five IgM-RF paraproteins, with known kappa chain amino acid sequences, suggested a relationship between the idiotope recognized by the hybridoma and the complementarity-determining regions. The serum of patients with rheumatoid arthritis contained idiotope positive material that bound specifically to a 17-109 immunoadsorbent column. Moreover, the 17-109 anti-idiotope antibody partially inhibited the binding to IgG of IgM-RF and IgA-RF in serum, but did not effect the binding to antigen of IgM and IgA anti-tetanus toxoid antibodies. These results suggest that a significant proportion of IgM-RF paraproteins share an idiotope located at or near the complementarity-determining regions of the kappa light chain. Human serum RFs include a kappa light chain family that is idiotopically related to the kappa chains on IgM-RF paraproteins.


Impact of pressure and temperature on CO2-brine-mica contact angles and CO2-brine interfacial tension: Implications for carbon geo-sequestration.
Precise characterization of wettability of CO2-brine-rock system and CO2-brine interfacial tension at reservoir conditions is essential as they influence capillary sealing efficiency of caprocks, which in turn, impacts the structural and residual trapping during CO2 geo-sequestration. In this context, we have experimentally measured advancing and receding contact angles for brine-CO2-mica system (surface roughness ∼12nm) at different pressures (0.1MPa, 5MPa, 7MPa, 10MPa, 15MPa, 20MPa), temperatures (308K, 323K, and 343K), and salinities (0wt%, 5wt%, 10wt%, 20wt% and 30wt% NaCl). For the same experimental matrix, CO2-brine interfacial tensions have also been measured using the pendant drop technique. The results indicate that both advancing and receding contact angles increase with pressure and salinity, but decrease with temperature. On the contrary, CO2-brine interfacial tension decrease with pressure and increase with temperature. At 20MPa and 308K, the advancing angle is measured to be ∼110°, indicating CO2-wetting. The results have been compared with various published literature data and probable factors responsible for deviations have been highlighted. Finally we demonstrate the implications of measured data by evaluating CO2 storage heights under various operating conditions. We conclude that for a given storage depth, reservoirs with lower pressures and high temperatures can store larger volumes and thus exhibit better sealing efficiency.


Synthesis and antisense properties of oligodeoxyribonucleotides containing C5-substituted arabinofuranosyluracil.
An oligodeoxyribonucleotide (ODN) containing three C5-substituted arabinofuranosyluracils was synthesized by the post-synthetic modification method from the ODN containing three C5-substituted 2,2'-anhydrouridines. The stability of the modified ODN/DNA duplex was lower than that of the corresponding normal duplex but that of the modified ODN/RNA duplex showed little change. The modified ODN could induce RNase H activity and was resistant against nuclease.


Effects of milnacipran, a 5-HT and noradrenaline reuptake inhibitor, on C-fibre-evoked field potentials in spinal long-term potentiation and neuropathic pain.
The analgesic action of 5-HT and noradrenaline reuptake inhibitors (SNRIs) on nociceptive synaptic transmission in the spinal cord is poorly understood. We investigated the effects of milnacipran, an SNRI, on C-fibre-evoked field potentials (FPs) in spinal long-term potentiation (LTP), a proposed synaptic mechanism of hypersensitivity, and on the FPs in a neuropathic pain model. C-fibre-evoked FPs by electrical stimulation of the sciatic nerve fibres were recorded in the spinal dorsal horn of anaesthetized adult rats, and LTP was induced by high-frequency stimulation of the sciatic nerve fibres. A rat model of neuropathic pain was produced by L5 spinal nerve ligation and transection. Milnacipran produced prolonged inhibition of C-fibre-evoked FPs when applied spinally after the establishment of LTP of C-fibre-evoked FPs in naïve animals. In the neuropathic pain model, spinal administration of milnacipran clearly reduced the basal C-fibre-evoked FPs. These inhibitory effects of milnacipran were blocked by spinal administration of methysergide, a 5-HT½ receptor antagonist, and yohimbine or idazoxan, α₂-adrenoceptor antagonists. However, spinal administration of milnacipran in naïve animals did not affect the basal C-fibre-evoked FPs and the induction of spinal LTP. Milnacipran inhibited C-fibre-mediated nociceptive synaptic transmission in the spinal dorsal horn after the establishment of spinal LTP and in the neuropathic pain model, by activating both spinal 5-hydroxytryptaminergic and noradrenergic systems. The condition-dependent inhibition of the C-fibre-mediated transmission by milnacipran could provide novel evidence regarding the analgesic mechanisms of SNRIs in chronic pain.


Protective effect of resveratrol against hydrogen peroxide-induced oxidative stress in bovine skeletal muscle cells.
The objective of this study was to investigate the protective effects and the underlying mechanisms of resveratrol (RES) against hydrogen peroxide (H2O2)-induced oxidative stress in bovine skeletal muscle cells (BMCs). Pretreatment of BMCs with RES prior to H2O2 exposure increased cell viability, attenuated reactive oxygen species, and stabilized the redox state. H2O2 exposure activated sirtuin type 1 (SIRT1) and nuclear factor E2-related factor 2 (NRF2)-mediated signaling pathways. Pretreatment with RES did not alter SIRT1-regulated genes but inhibited the upregulation of NRF2, whereas enhanced heme oxygenase 1 (HO-1) expression. Pretreatment with RES prior to H2O2 exposure failed to suppress NRF2 expression when NRF2 was knocked down by RNA interference. However, HO-1 expression still could be induced by RES. These results suggest that RES has benifical effects against oxidative stress. NRF2-mediated pathway play an important role, and HO-1 upregulation is the key process in RES regulation. RES may be used as a therapeutic agent for meat quality improvement in beef cattle.


Endobronchial metastases from prostatic carcinoma.
Prostatic carcinoma presenting with pulmonary symptoms is unusual. We describe the case of a 59-year-old man whose disseminated prostate cancer was diagnosed with bronchoscopy. To our knowledge, this represents the second reported case of prostate cancer that manifested with endobronchial symptoms. The importance of this entity and clinical and therapeutic aspects are also discussed.


Early childhood antibiotic utilization for infants discharged from the neonatal intensive care unit.
To determine antibiotic utilization for NICU infants, as compared to non-NICU infants, in the first 3 years after birth hospital discharge. Retrospective observational study using data from Medicaid Analytic Extract including 667 541 newborns discharged from 2007-2011. Associations between NICU admission and antibiotic prescription were assessed using regression models, adjusting for confounders, and stratified by gestational age and birth weight. 596 999 infants (89.4%) received ≥1 antibiotic, with a median of 4 prescriptions per 3 person-years (IQR 2-8). Prescribed antibiotics and associated indication were similar between groups. Compared to non-NICU infants (N = 586 227), NICU infants (N = 81 314) received more antibiotic prescriptions (adjusted incidence rate ratio 1.08, 95% confidence interval [CI] (1.08,1.08)). Similar results were observed in all NICU subgroups. Antibiotic utilization in early childhood was higher among infants discharged from NICUs compared to non-NICU infants.


Increased production of procoagulant activity (tissue factor) by human peripheral blood monocytes after Intralipid infusion.
Intralipid can produce functional and structural changes in the mononuclear phagocyte system. We have investigated the effect of Intralipid on the capacity of peripheral blood human monocytes to produce procoagulant activity when incubated in short term cultures. Twenty-three patients were studied before and after a single infusion of Intralipid 10%. Procoagulant activity was measured on isolated mononuclear cells after incubation (4 h at 37 degrees C) with and without endotoxin, using a one-stage clotting assay. Mononuclear cells obtained after Intralipid infusion produced significantly increased procoagulant activity as compared to their pre-infusion control samples (p < 0.005). Similar results were obtained when freshly collected whole blood was incubated with and without endotoxin (4 h at 37 degrees C) and procoagulant activity was measured on subsequently isolated mononuclear cells (p < 0.005). In all instances procoagulant activity was identified as tissue factor. Patients in the need of Intralipid are often at increased risk for thromboembolic complications and/or disseminated intravascular coagulation because of malignant disease, surgery or infection and there is evidence that the procoagulant activity of mononuclear phagocytes could play a major role in these processes. Our findings suggest that Intralipid might cause a further accentuation of the thrombotic tendency as a result of increased procoagulant activity.


Virtual 2D mapping of the viral proteome reveals host-specific modality distribution of molecular weight and isoelectric point.
A proteome-wide study of the virus kingdom based on 1.713 million protein sequences from 19,128 virus proteomes was conducted to construct an overall proteome map of the virus kingdom. Viral proteomes encode an average of 386.214 amino acids per protein with the variation in the number of protein-coding sequences being host-specific. The proteomes of viruses of fungi hosts (882.464) encoded the greatest number of amino acids, while the viral proteome of bacterial host (210.912) encoded the smallest number of amino acids. Viral proteomes were found to have a host-specific amino acid composition. Leu (8.556%) was the most abundant and Trp (1.274%) the least abundant amino acid in the collective proteome of viruses. Viruses were found to exhibit a host-dependent molecular weight and isoelectric point of encoded proteins. The isoelectric point (pI) of viral proteins was found in the acidic range, having an average pI of 6.89. However, the pI of viral proteins of algal (pI 7.08) and vertebrate (pI 7.09) hosts was in the basic range. The virtual 2D map of the viral proteome from different hosts exhibited host-dependent modalities. The virus proteome from algal hosts and archaea exhibited a bimodal distribution of molecular weight and pI, while the virus proteome of bacterial host exhibited a trimodal distribution, and the virus proteome of fungal, human, land plants, invertebrate, protozoa, and vertebrate hosts exhibited a unimodal distribution.


The effect of heavy metal ions on the rate of decomposition of N-ethyl-N-nitrosourea and other carcinogenic N-nitrosamides.
The decomposition of ethylnitrosourea (ENU) in aqueous solution is enhanced by Cu2+ ions. Ni2+ shows a similar, but less pronounced effect. The decomposition rate of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), a compound known to be relatively stable in aqueous solution, is strongly enhanced by the addition of Cu2+ and to a smaller extent also by Ni2+ ions. On the other hand the stability of N-methyl-N-nitrosourethane is not influenced by heavy meatal ions. The influence of Cu2+ ions on the decomposition rate of ENU is similar to that of OH-anions, influencing the reaction kinetics on a molar basis. The increase in decomposition rate of ENU by copper ions is not seen in the presence of blood serum or other complexing agents. The results are discussed in relation to the known enhancement in toxicity and carcinogenicity of ENU by heavy metal salts in animal experiments.


[Microbial colonization and various cleaning procedures for orthodontic appliances].
The cleaning of removable appliances was analysed in three groups: 1. cleaning with tooth-brush/toothpaste, 2. self-acting cleansing agent, 3. ultrasonic treatment. In the same patient group identical plates were fitted each for one month and cleaned by the different procedures. The microbial population and the cleansing effects were analysed by scanning electron microscopy. The findings shows clearly, that the toothbrush alone is unsatisfactory for achieving effective decontamination in the hygiene-critical areas of the plates. In contrast to this cleansing tablets and ultrasonic treatment were more effective in plaque-accumulating areas. None of the cleansing procedures effected complete decontamination of the removable appliances.


Analysis of first apheresis services in Ghana-Greater Accra Regional Hospital.
At the combined American Society for Apheresis (ASFA) annual meeting and World Apheresis Association (WAA) Congress in 2014, it was observed that there were significant disparities with regard to the access of apheresis services within and across developing countries, with only few of such facilities available in Africa; notably South Africa and Nigeria. In 2019, Bone Marrow Transplantation (BMT) Unit-Ghana, acquired an apheresis machine. By the collaboration between BMT-Ghana, the Greater Accra Regional Hospital (GARH) and the Ministry of Health (Ghana), apheresis services is now available in Ghana. The aim of this paper is to present an analysis of apheresis services so far in Ghana. A 12-month period from 2019 to 2021 was examined (less the period of the COVID-19 outbreak when the Unit was virtually at a standstill). The electronic database and hard copies of documented activities were analysed. Basic information on demographics and procedure types and counts was used. The retrospective study encompassed data of 43 patients. Two (2) patients came from the West Africa sub-region (Nigeria and Cameroon) with the rest from 6 out of the 14 regions of Ghana (Greater Accra, Western, Central, Eastern, Ashanti, Volta). The essential nature of the apheresis services being the first in Ghana, brought patients as far as 315 km from the hinterlands to the Unit. Ages ranged from 2-52 years with a mean of 16.3 ± 15.3 years. Slightly more females (n = 23, 53%) received services than males (n = 20, 47%). Eighty-six percent (n = 37, 86%) of the patients were sickle cell patients referred to the Unit. Red Blood Cell exchange (RBCx) accounted for 87% (n = 40), of the 46 procedure counts followed by Continuous Mononuclear Cell Collection (CMNC) (n = 4, 9%) and lastly, Therapeutic Plasma Exchange (TPE) (n = 2, 4%). Ghana can now be counted among African countries offering apheresis services and the GARH is acknowledged as the only hospital in the country with this facility, thus improving patient care significantly.


Long Non-coding RNA LOC285194 Promotes Epithelial Ovarian Cancer Progression via the Apoptosis Signaling Pathway.
To explore the molecular mechanism and clinical significance of a newly identified lncRNA LOC285194 in epithelial ovarian cancer (EOC). LOC285194 transcript levels were analyzed in EOC cells compared to normal cells. Small interfering RNAs were used to suppress LOC285194 expression. Levels of apoptosis-related proteins were determined by western blot. LOC285194 expression in ovarian cancer and non-tumor tissues were compared with clinicopathologic and survival data. Knockdown of LOC285194 decreased cell migration and proliferation, enhanced reactive oxygen species production and resulted in increased levels of proteins of the extrinsic apoptotic signaling pathway. LOC285194 expression level was higher in ovarian cancer tissues compared to control. Overall survival was significantly shorter in patients with high LOC285194 expression. Lymph node metastasis and high LOC285194 expression were significant prognostic factors of mortality (HR=4.614 and 5.880; p=0.026 and p=0.002, respectively). LOC285194 can promote the progression of EOC via an anti-apoptotic mechanism. It may serve as a novel biomarker for predicting prognosis of EOC.


Glycyrrhizin inhibits interleukin-8 production and nuclear factor-kappaB activity in lung epithelial cells, but not through glucocorticoid receptors.
This study was designed to examine the glucocorticoid-like inhibitory effect of glycyrrhizin (GL) on interleukin (IL)-8 production in A549 lung epithelial cells. GL, as well as dexamethasone (DEX) inhibited both tumor necrosis factor (TNF)-alpha- and IL-1beta-induced IL-8 production, mRNA expression, and promoter activity in A549 cells. Both GL and DEX inhibited transactivation of nuclear factor (NF)-kappaB, without inhibiting translocation of the NF-kappaB p65 subunit to the nucleus. However, the effect of GL was insensitive to RU486, a GR antagonist, and to GR knockdown by siRNA. Furthermore, only GL inhibited DNA binding of p65 to the IL-8 promoter region. These findings indicated that GL had a glucocorticoid-like inhibitory effect on IL-8 production via a mechanism that differs from that of glucocorticoids.


Evaluation of surface characterization and mechanical features of resin-matrix ceramics before and after different surface treatments.
Surface treatments (STs) required for micromechanical interlocking can lead to alterations in the surface characterization and mechanical features of the resin-matrix ceramics (RMCs), which may jeopardize the long-term outcome of an indirect restoration. However, evidence on this issue is lacking. The purpose of this in vitro study was to assess the influence of different STs on the surface roughness (SR), water contact angle (WCA), and flexural strength (FS) of RMCs. Two hundred rectangular plates (12×14×1 mm) were prepared from 5 different RMC ingots, including a polymer-infiltrated ceramic network (Vita Enamic [VE]), 2 resin nanoceramics (Lava Ultimate [LU], Grandio Blocks [GB]), a flexible nanoparticle-filled resin (GC Cerasmart [GC]), and a reinforced composite resin (Brilliant Crios [BC]). Plates of each RMC group were further divided into 4 subgroups according to the ST applied: Control, no treatment (C); airborne-particle abrasion with aluminum oxide particles (APA); 2W- and 3W-Er,Cr:YSGG laser irradiations (LI2W, LI3W) (n=10 per ST). The SR (Ra) of each plate was recorded with a contact profilometer. WCAs (θ) of distilled water on the plates were determined by using the sessile-drop method. The FS (MPa) of each plate was measured with a universal testing machine. Data acquired for SR, WCA, and FS were statistically analyzed (α=.05). Weibull statistics were also conducted to determine the reliability of each material. The 2-way ANOVA showed that SR, WCA, and FS values were significantly influenced not only by all tested variables but also by their interaction terms (P<.001). All STs significantly increased the SR values (P<.05). Maximum and minimum SR values were recorded in GC-LI3W (7.06 ±0.16) and GC-C (0.07 ±0.02) groups. After STs, WCA values significantly diminished (P<.05). Maximum and minimum WCA values were recorded in LU-C (61.74 ±2.45) and VE-APA (40.38 ±1.56) groups. All STs significantly reduced the FS values (P<.05). The upper and lower FS bounds were 140.7 ±17.07 and 60.66 ±6.31, respectively, set by VG-C and GC-APA. Weibull distribution indicated that the untreated groups presented the highest m values. Among the treated groups, BC-LI3W demonstrated superior reliability (m=14.04). APA for LU, LI2W for VG and BC, and LI3W for GC and VE can be preferred. Although APA increased the SR and provided more wettable surfaces, it caused considerable loss of FS. Therefore, LI can be recommended as a safer ST for RMCs.


A sequence-based computational approach to predicting PDZ domain-peptide interactions.
The PDZ domain is one of the most ubiquitous protein domains that is involved in coordinating signaling complex formation and protein networking by reversibly interacting with multiple binding partners. It has been linked to many devastating diseases such as avian influenza, Fraser syndrome, Usher syndrome and Dejerine-Sottas neuropathy. Understanding the selectivity of PDZ domains can help elucidate how defects in PDZ proteins and their binding partners lead to human diseases. Since experimental methods to determine the interaction specificity of the PDZ domains are expensive and labor intensive, an accurate computational method is thus needed. Our developed support vector machine-based predictor using dipeptide composition is shown to qualitatively predict PDZ domain-peptide interaction with a high accuracy rate. Furthermore, since most of the dipeptide compositions are redundant and irrelevant, we propose a new hybrid feature selection technique to select only a subset of these compositions for interaction prediction. The experimental results show that only approximately 25% of dipeptide features are needed and that our method improves the prediction results significantly. The selected dipeptide features are also analyzed and shown to play important roles in specificity patterns of PDZ domains. Our method is based only on primary sequence information, and it can be used for the research of drug target and drug design in identifying PDZ domain-ligand interactions. This article is part of a Special Issue entitled: Computational Proteomics, Systems Biology & Clinical Implications. Guest Editor: Yudong Cai.


Single-unit characteristics in the auditory midbrain of the immobilized grassfrog.
The anuran auditory midbrain of the grassfrog (Rana temporaria L.) was studied by a combined spectro-temporal analysis of sound preceding neural events. From the spectro-temporal sensitivities (STS) estimates of best frequencies (BF) and latencies (LT) were derived. Several types of STSs were observed: monomodal excitatory STSs comprised about half of the cases. Bimodal excitatory STSs, i.e. STSs with two discrete excitation regions, were observed in about 25%. Trimodal and broadly tuned STSs comprised about 5%. The remaining 20% of the STSs were characterized by inhibitory phenomena such as pure inhibition, sideband inhibition and post-activation inhibition. The distribution of best frequencies matches the frequency spectrum of the animal's vocalizations. A relative absence of monomodal units was noted in the mid frequency range. The distribution of latencies was bimodal over the range 7-108 ms. For each unit 6 functional parameters were determined; besides BF and LT these were: form of the STS (i.e. monomodality versus multimodality), spontaneous activity, binaural interaction, and firing mode (i.e. sustained versus transient) upon continuous noises stimulation. In addition, two structural parameters were considered: location in the torus and action potential waveform. Large correlations appeared between LT and action potential waveform, and between BF and binaural interaction type. Tonotopy was not found. A comparison was made between results from this study with a previous study on lightly anesthetized grassfrogs, using the same stimulus paradigms (D.J. Hermes et al. (1981): Hearing Res. 5, 147-178; D.J. Hermes et al. (1982): Hearing Res. 6, 103-126). Spontaneous activity, inhibitory phenomena and complex STSs were common using immobilization, whereas these have hardly been observed using anesthesia. Furthermore, interdependencies between the neural characteristics are substantially weaker for the immobilized preparation.


Purification and properties of cytochrome P-450 (P-450lun) catalyzing steroid 11 beta-hydroxylation in Curvularia lunata.
Addition of 11-deoxycortisol to the culture medium of Curvularia lunata induced the increase of cytochrome P-450 content and steroid 11 beta-hydroxylase activity. The enzyme in cell-free extract produces cortisol from 11-deoxycortisol in the presence of NADPH and O2. The enzyme was partially stabilized by glycerol, 11-deoxycortisol, GSH and PMSF. The hydroxylation activity was strongly inhibited by carbon monooxide and sulfhydryl reagents. Cytochrome P-450 located on the microsomal fraction was solubilized with Triton X-100 and sodium cholate and purified to apparent homogeneity by column chromatography. The purified cytochrome P-450 (P-450lun) has a molecular mass of 60 kDa and exhibits the absorption maximum at 392 nm in the spectrum of oxidized form in the presence of 11-deoxycortisol. The reduced CO difference spectrum has a maximal peak at 448 nm. 11 beta-Hydroxylation of 11-deoxycortisol was reconstituted by cytochrome P-450lun, C. lunata NADPH-cytochrome P-450 reductase and DLPC in the presence of NADPH and O2 with a turnover number of 207 nmol/min per nmol of cytochrome P-450. The reductase and DLPC could be partially replaced with the enzyme purified from yeast or pig testis microsome and lipids purified from C. lunata, respectively. P-450lun catalyzes bifunctionally 11 beta- and 14 alpha-hydroxylations of 11-deoxycortisol. Deoxycorticosterone, progesterone, androstenedione and testosterone are hydroxylated in the similar manner.


A cytochemical and immunofluorescence study of endocrine cells in the gut of the ascidian Styela clava.
Strong secretin-like immunofluorescence has been demonstrated in endocrine-like cells from the gastric epithelium of Styela. These cells also stain with lead haematoxylin and exhibit a brilliant formaldehyde-induced fluorescence, but do not show any other cytochemical features characteristics of the mammalian APUD series. Tests with antisera to glucagon, gastrin and somatostatin all proved negative. In the oesophagus tests with all four antisera proved negative. The significance of these results is discussed in relation to the phylogeny of vertebrate gastro-intestinal hormones.


Tufted capuchins (Cebus apella) attribute value to foods and tools during voluntary exchanges with humans.
This research examined exchange and value attribution in tufted capuchin monkeys ( Cebus apella). We presented subjects with opportunities to obtain various foods and a tool from an experimenter in exchange for the foods or tool in the subjects' possession. The times elapsed before the first chow biscuits were expelled and/or an exchange took place were recorded as the dependent measures. Laboratory chow biscuits, grapes, apples, and a metal bolt (a tool used to probe for syrup) were used as experimental stimuli. The subjects demonstrated the ability to recognize that exchanges could occur when an experimenter was present with a desirable food. Results indicate that subjects exhibited significant variation in their willingness to barter based upon the types of foods that were both in their possession and presented by the experimenter. Subjects more readily traded chow biscuits for fruit, and more readily traded apples for grapes than grapes for apples. During the exchange of tools and food, the subjects preferred the following in descending order when the probing apparatus was baited with sweet syrup: grapes, metal bolts, and chow biscuits. However when the apparatus was not baited, the values changed to the following in descending order: grapes, chow, and metal bolts. These results indicate that tufted capuchins recognize opportunities to exchange and engage in a simple barter system whereby low-valued foods are readily traded for more highly valued food. Furthermore, these capuchins demonstrate that their value for a tool changes depending upon its utility.


A survey analysis of knowledge levels of urologists about radiation safety and fluoroscopy use.
To evaluate the awareness of the use of fluoroscopy in endourological procedures, as well as the theoretical and practical applications of preventive measures. Between May 2018 and April 2019, a 26-question survey prepared using Google Docs was sent to urologists via email. Personal information, radiation training and behaviours related to radiation and fluoroscopy usage, and the use of protective equipment were queried. A total of 226 participants fully completed and returned the email survey. Of the 226 participants, 78 (34.5%) were academics, 44 (19.4%) were residents while 104 (46.1%) were experts. More than 60% of the participants stated that they participated in the operation requiring less than five fluoroscopy use per week. The majority of operations requiring fluoroscopy consisted of endourological procedures. The lead apron was used by 93% of the participants, but the use of protective glasses and gloves was very low (3.5%). The majority of academicians, experts and residents did not use dosimeters (76.9%, 82.7% and 81.8%, respectively). More than 50% of the participants did not have literature information about the harmful effects of radiation with the use of fluoroscopy. The most common complaints on the day of fluoroscopy were fatigue and headache. The lack of information regarding the radiation protection measures and harmful effects of radiation is common among urologists in Turkey. Therefore, systematic training programs on fluoroscopy use and radiation exposure should be provided during urology residency.


Development of high-utilization honeycomb-like α-Ni(OH)2 for asymmetric supercapacitors with excellent capacitance.
The low utilization rate of active materials has been a critical obstacle for the industrialization of ultracapacitors. In this study, a thin layer of cross-structured ultrathin α-Ni(OH)2 nanosheets was successfully grown in situ on the surface of a nickel foam as a high-conductivity framework by a vibratory water bath route under a low temperature (80 °C) and mild conditions. Combining the ultrathin α-Ni(OH)2 nanosheets and ultrashort electron transport, the strategy of a perfect intercalation structure of α-Ni(OH)2 and a thin layer of active material on a continuous conductive framework resulted in a high utilization rate of active material, which further achieved high specific capacitance of 213.55 F g-1 at 1 A g-1 in a two-electrode system and high capacitance retention from three to two electrode system (753.79 F g-1 at 1 A g-1 in the three-electrode system). Meanwhile, the device also achieved high energy density of 74.94 W h kg-1 at power density of 197.4 W kg-1 and still retained 24.87 W h kg-1 at power density of 3642 W kg-1.