Issues in reflection and debriefing: how nurse educators structure experiential activities.
Experiential learning is particularly useful in vocational education programs where theory needs to be linked to practice. Although experiential learning is often advocated in nursing education and the importance of debriefing and reflection is almost always espoused, the focus in the literature has tended to be on detailed descriptions of the action phase with little close analysis of how the reflective phase is facilitated. The Lewinian model described by Kolb [Experiential Learning. Experience as Source of Learning and Development, Prentice-Hall, New Jersey, 1984] and the structuring approach suggested by Thiagarajan [Experiential Learning Packages, Prentice-Hall, Englewood Cliffs, NJ, 1980] have been used as the theoretical context for an exploration of how nurse teachers describe their facilitation of the debriefing and reflective phases of experiential learning activities. Explication of the entire planned experiential learning experience is important for increasing the chances of the student being able to close the experiential learning loop. The more covert reflective phases for facilitating experiential learning are crucial and if neglected, or inexpertly and insensitively handled, may at best lead to poor learning outcomes or at worst lead to emotional damage and ;unfinished business' for the student. Interviews with eight experienced university educators elicited descriptions of how they constructed experiential activities with special reference to their descriptions of how the debriefing or reflective phases were structured.


Caries prevalence, oral hygiene and orthodontic status of Saudi Bedouin children.
The objectives of the study were to determine caries prevalence, oral hygiene and orthodontic status of Bedouin children in a desert around Al-Qasseem Region of Saudi Arabia. One hundred and fifty three children were examined for caries, oral hygiene and orthodontic status with mirror and explorer utilizing natural light. These children were divided into two groups for analyses. The primary dentition group consisted of 77 children, 39 (50.6%) male and 38 (49.4%) female with a mean age of 4.0 (+/- 1.4) years. The mixed dentition group consisted of 76 children, 67 (88.2%) male and 9 (11.8%) female with a mean age of 9.7 (+/- 2.9) years. In Primary dentition group, 16 (20.8%) children were caries positive and mean DMFT was 0.91 (+/- 2.42). There was a highly significant relation (p < .001) between oral hygiene and caries. In the mixed dentition group, 15 (19.7%) children were caries positive. The mean DMFT and DMFT scores for these children were 0.72 (+/- 1.96) and 0.74 (+/- 1.48) respectively. There was a significant relation (P > .01) between oral hygiene and caries. One hundred and fifty one (98.6%) children had class I molar relation and 2 (1.4%) children had class II molar relation. Anterior open bite, anterior crossbite and posterior crossbite were found in one case (0.7%) each. The caries experience of these Bedouin children was low both in terms of prevalence and severity. There was a significant relation between oral hygiene and caries. The orthodontic problems were almost nonexistent in the study population.


Effective mammogram classification based on center symmetric-LBP features in wavelet domain using random forests.
Mammogram classification is a crucial and challenging problem, because it helps in early diagnosis of breast cancer and supports radiologists in their decision to analyze similar mammograms out of a database by recognizing the classes of current mammograms. This paper proposes an effective method for classifying mammograms using random forests with wavelet based center-symmetric local binary pattern (WCS-LBP). To classify mammograms, multi-resolution CS-LBP texture characteristics from non-overlapping regions of the mammograms are captured. Further, we examine most relevant features using support vector machine-recursive feature elimination (SVM-RFE). Finally, we feed the selected features to decision trees and construct random forests which are an ensemble of random decision trees. Using wavelet based local CS-LBP features with random forest, we classify the test images into different categories having the maximum posterior probability. The proposed method shows the improved performance as compared with other variant features and state-of-art methods. The obtained performance measures are 97.3% accuracy, 97.3% precision, 97.2% recall, 97.2% F-measure and 94.1% Matthews correlation coefficient (MCC).


Cardiovascular Disease Burden Attributable to High Body Mass Index in Taiwan.
Studies on disease burden in Taiwan are lacking. We aimed to quantify the burden of cardiovascular disease (CVD) attributable to high body mass index (BMI) in Taiwan. Using a comparative risk assessment approach from the Global Burden of Disease study, we estimated the population attributable fraction (PAF), attributable CVD burden, and disability-adjusted life years (DALYs) according to sex, age, and area of residence in Taiwan. The BMI distribution for the population was obtained from the National Health Interview Survey in 2013. CVD was defined as an ischemic heart disease or stroke. The attributable PAF for CVD from high BMI was 18.0% (19.6% in men and 15.6% in women), and it was highest (42.7%) in those aged 25-30 years. Adults aged 60-65 years had the highest absolute DALYs (11,546). The average relative age-standardized attributable burden was 314 DALYs per 100,000 person-years, and it was highest in those aged 75-80 years (1,407 DALYs per 100,000 person-years). Those living in Taitung County had the highest PAF of 21.9% and the highest age-standardized attributable burden (412 DALYs). In Taiwan, an 18% reduction in CVDs could be achieved if obesity/overweight was prevented. Prevention was most effective in early adulthood. The absolute CVD burden from obesity/overweight was highest in middle-aged men, and the relative burden was highest in older adults. Resource allocation in targeted populations and specific areas to eliminate CVD and health inequities is urgently required.


Kidney Function, Self-Reported Symptoms, and Urine Findings in Nicaraguan Sugarcane Workers.
An epidemic of CKD in Central America predominantly affects males working in certain industries, including sugarcane. Urinary tract infections are commonly diagnosed among men in Nicaragua, who often receive antibiotics and nonsteroidal anti-inflammatory drugs for urinary symptoms. We followed 251 male Nicaraguan sugarcane workers in seven job tasks over one harvest and measured urine dipstick parameters, kidney injury biomarkers, and eGFR. We administered a questionnaire about urinary symptoms, health-related behaviors, and medication history. We cultured urine in a subset of workers. The study population was composed of factory workers (23%), cane cutters (20%), irrigators (20%), drivers (16%), agrichemical applicators (12%), seeders/reseeders (6%), and seed cutters (4%). The mean age of participants was 33.9 years, and mean employment duration was 10.1 years. Cane cutters reported higher proportions of urinary-related symptoms compared with agrichemical applicators, irrigators, and seeders/reseeders. Seed cutters were more likely to take antibiotics (22%), whereas drivers and seeders/reseeders were more likely to take pain medications (27% and 27%, respectively). Proteinuria was uncommon, whereas dipstick leukocyte esterase was relatively common, especially among cane cutters, seed cutters, and seeders/reseeders (33%, 22%, and 21% at late harvest, respectively). Dipstick leukocyte esterase at late harvest was associated with a 12.9 ml/min per 1.73 m2 (95% CI, -18.7 to -7.0) lower mean eGFR and 2.8 times (95% CI, 1.8 to 4.3) higher mean neutrophil gelatinase-associated lipocalin. In general, workers who reported urinary-related symptoms had higher mean kidney injury biomarker levels at late harvest. None of the workers had positive urine cultures, including those reporting urinary symptoms and/or with positive leukocyte esterase results. Amoxicillin, ibuprofen, and acetaminophen were the most commonly used medications. Job task is associated with urinary symptoms and dipstick leukocyte esterase. Urinary tract infection is misdiagnosed based on leukocyte esterase, which may be an important predictor of kidney outcomes.


ACTH expression in synovium of patients with rheumatoid arthritis and Lewis rats with adjuvant arthritis.
Abstract Adrenocorticotropic hormone (ACTH) and another pro-opiomelanocortin-derived neuropeptide, β-endorphin (β-End), are stimulated by corticotropin-releasing hormone (CRH) at the anterior pituitary. CRH and β-End have predominantly proinflammatory effects in peripheral inflammatory sites. We have supposed that inflammatory stimuli develop ACTH as well as β-End. In this study, we investigated the expression of ACTH in inflamed synovial tissue from patients with rheumatoid arthritis (RA) and osteoarthritis (OA), and at inflammatory joints with adjuvant-induced arthritis (AA) in female Lewis (LEW/N) rats. The expression of ACTH immunostaining was significantly greater in synovium of RA patients than in that of OA patients (P < 0.0001), and correlated with the extent of inflammatory mononuclear cell infiltration. Extensive and intense intracellular ACTH immunostaining, which correlated with the advance in arthritis score, was observed in the synovial lining layer, inflammatory mononuclear cells, and fibroblast-like cells of synovium and chondrocytes in LEW/N rats with AA. In addition, we performed double immunostaining of the same sections from arthritic joints in rats with anti-ACTH and anti-CRH antibodies. ACTH and CRH colocalized in inflammatory mononuclear cells and fibroblast-like cells. ACTH may play a role in the pathogenesis of RA as well as CRH.


Effect of complement and viral filtration on the neutralization of respiratory syncytial virus.
The addition of 10 hemolytic units of guinea pig complement has been shown to enhance the neutralizing capacity of respiratory syncytial (RS) immune sera produced in guinea pigs and ferrets. This same immune sera, when tested without complement, had little or no neutralizing capacity. The addition of complement to RS immune horse serum did not significantly increase its neutralizing capacity. Immune horse serum effectively neutralized RS virus without complement. Other studies indicated that a 50% tissue culture infective dose of between 30 and 100 should be used in RS serum neutralization tests and that incubation should be for 90 to 105 min at room temperature. The neutralizing capacity of guinea pig immune serum was not increased by the use of filtered virus. The rate of virus neutralization, however, was increased with the addition of 10 hemolytic units of complement. The neutralizing capacity of RS immune horse serum was much greater for filtered than for unfiltered RS virus. The addition of complement increased the rate of virus neutralization but did not increase the neutralizing capacity of the horse immune serum.


Monogenean community structure of Oreochromis niloticus in relation to heavy metal pollution and host reproductive cycle.
The community structure of monogenean parasites of Oreochromis niloticus and its relation to the variations of heavy metal concentrations in water and the host reproductive cycle (gonadosomatic index, GSI) was studied. Fish were collected from Fishermen Lake, Ismailia. Monogenea community consisted of seven species, Cichlidogyrus halli typicus (57.8%), C. thurstonae (35.3%), C. ergensi (13.8 %), C. tiberianus (16.4%), C. arthracanthus (13.8%), Scutogyrus longicornis (22.4%) and Gyrodadtylus cicchlidarum (18.9 %). The overall mean species richness per host was 4.45 +/- 0.34. Responses of monogenea regarding their prevalence, abundance and intensity to the host sex and seasonal variations varied according to the species. Monogenean community showed different responses to the heavy metal concentrations and GSI. Positive correlations were found between species richness and both gonadosomatic index (rs = 0.2, P = 0.03) and Cd concentrations (rs = 0.89, P=0.04). Prevalence of C. halli typicus and C. thurstonae showed significant negative and positive correlations, respectively with the levels of Cu and Pb. G. cicchlidarus showed significant positive correlation with Cd level. The abundance and intensity of those species showed also correlations with the metal concentrations. Other monogenean species did not show any response to the metal levels such as C. tiberianus. Zn did not show any effect on the infection parameters of any species of monogenean community. The possibility of using some monogenean species to act as indicators for environmental pollution was discussed.


Ovarian mesothelial tumors and herbicides: a case-control study.
The ovarian cancer risk from herbicide exposure has been studied in a hospital-based, case-control study after some of these compounds have been shown to be carcinogenic for animals. This study includes 60 cases of primary mesothelial ovarian tumors and 127 controls with non-ovarian malignancies drawn from the same file and matched by year of diagnosis, age and residence. A positive association (relative risk 4.38) has been found between herbicide exposure and ovarian mesotheliomas.


Cloning, Expression, and Characterization of budC Gene Encoding meso-2,3-Butanediol Dehydrogenase from Bacillus licheniformis.
The budC gene encoding a meso-2,3-butanediol dehydrogenase (BlBDH) from Bacillus licheniformis was cloned and overexpressed in Escherichia coli BL21(DE3). Sequence analysis reveals that this BlBDH belongs to short-chain dehydrogenase/reductase (SDR) superfamily. In the presence of NADH, BlBDH catalyzes the reduction of diacetyl to (3S)-acetoin (97.3% ee), and further to (2S,3S)-2,3-butanediol (97.3% ee and 96.5% de). Similar to other meso-2,3-BDHs, it shows oxidative activity to racemic 2,3-butanediol whereas no activity toward racemic acetoin in the presence of NAD(+). For diacetyl reduction and 2,3-butanediol oxidation, the pH optimum of BlBDH is 5.0 and 10.0, respectively. Unusually, it shows relatively high activity over a wide pH range from 5.0 to 8.0 for racemic acetoin reduction. BlBDH shows lower K m and higher catalytic efficiency toward racemic acetoin (K m = 0.47 mM, k cat /K m = 432 s(-1)·mM(-1)) when compared with 2,3-butanediol (K m = 7.25 mM, k cat /K m = 81.5 s(-1)·mM(-1)), indicating its physiological role in favor of reducing racemic acetoin into 2,3-butanediol. The enzymatic characterization of BlBDH provides evidence for the directed engineering of B. licheniformis for producing enantiopure 2,3-butanediol.


Testing an algebraic model of self-reflexion.
Self-reflexion is the conscious process of taking the position of an observer in relation to one's own thoughts, feelings, and experiences. Building on the work of Lefebvre, Lefebvre, and Adams-Webber, we used a formal algebraic model of self-reflexion to derive several predictions regarding the frequencies with which individuals would rate themselves and others positively on bipolar scales anchored by adjective terms. The current results from 108 participants (41 men, 67 women; M age= 20.2 yr.) confirmed two predictions derived from the model. Three other predictions, however, were not supported even though the observed frequencies were close to the predicted values. Although not as promising as results reported by Lefebvre, et al., these mixed findings were interpreted as encouraging support for the validity of Lefebvre's algebraic model of self-reflexion. Differences between the current methods and those from previous investigations were also examined, and methodological implications for further studies were discussed.


A randomized-controlled trial of using a book of metaphors to reconceptualize pain and decrease catastrophizing in people with chronic pain.
Reconceptualization of pain and reduction of pain-related catastrophizing are primary objectives in chronic pain rehabilitation. Teaching people about the underlying biology of pain has been shown to facilitate these objectives. The objective of this study was to investigate whether written metaphor and story can be used to increase knowledge of the biology of pain and reduce pain-related catastrophizing. In this randomized single-blind partial cross-over controlled trial, 79 people with chronic pain received either a booklet of metaphors and stories conveying key pain biology concepts or a booklet containing advice on how to manage chronic pain according to established cognitive-behavioral principles. The primary outcome variables, pain biology knowledge and catastrophizing, were measured before randomization, at 3 weeks and at 3 months, at which time the control group was crossed over to receive the metaphors and stories booklet. Pain and disability were secondary outcome variables. The Metaphors group showed larger changes in both variables (time × group interactions: P < 0.01, effect size Cohen d = 0.7 for catastrophizing and 1.7 for pain biology knowledge). Gains were maintained for at least 3 months. Changes were replicated in the Advice group when crossed over. There was no change in pain or self-reported disability in either group. We conclude that providing educational material through metaphor and story can assist patients to reconceptualize pain and reduce catastrophizing. Metaphor and story could be used as a precurser to other interventions that target functional capacity.


Nutrition in chronic disease management in the elderly.
Older Americans experience chronic disease at rates well above other segments of our society. Rates of health services use are also 2 to 3 times that of younger age groups. The most rapidly growing segments of America's aging population are also its most nutritionally vulnerable-women, minorities, and those 85 years of age and older. The routine incorporation of nutrition screening and intervention into chronic disease management protocols will lower healthcare services usage, decrease healthcare costs, help relieve the burden of human suffering experienced by older Americans with chronic disease, and improve quality of life for our nation's elders.


Estimated donor glomerular filtration rate is the most important donor characteristic predicting graft function in recipients of kidneys from live donors.
We hypothesized that predictors of outcome in live donor transplants were likely to differ significantly from deceased donor transplants, in which cold ischaemia time, cause of donor death and other donor factors are the most important predictors. The primary aim was to explore the independent predictors of graft function in recipients of live donor kidneys (LDK). Our secondary aim was to determine which donor characteristics are the most useful predictors. A retrospective analysis was undertaken of all patients receiving live donor (n = 206) renal transplants at our institution between 31 May 1994 and 15 October 2002. Twelve patients were excluded from the analysis. Follow-up was completed on all patients until graft loss, death or 22 November 2003. We explored predictors of Nankivell glomerular filtration rate (GFR) at 6 months by multivariate linear regression. In the 194 patients studied, the mean recipient 6-month Nankivell GFR was 59 +/- 15 ml/min/1.73 m(2). Independent predictors of recipient GFR in at 6 months were donor Cockcroft-Gault GFR (CrCl; beta 0.16; CI 0.13 to 0.29; P < 0.0001), steroid resistant rejection (beta-6.07; CI -12.05 to -0.09; P = 0.006) and delayed graft function (DGF) (beta-10.0; CI -19.52 to -0.49; P = 0.039). Renal function in an LDK transplant recipients is predicted by donor GFR, episodes of steroid resistant rejection and DGF. Importantly, donor Cockcroft-Gault GFR is the most important characteristic for predicting the recipient renal function.


Genistein and menaquinone-4 treatment-induced alterations in the expression of mRNAs and their products are beneficial to osteoblastic MC3T3-E1 cell functions.
The aim of the present study was to determine the molecular basis of the beneficial effects of genistein and/or menaquinone‑4 (MK‑4) on bone quality. Initially, 1 µM genistein was applied to MC3T3‑E1 cells for 24 h and the upregulated mRNAs that were detected by microarray were selected for further examination by reverse transcription‑quantitative‑polymerase chain reaction. Among them, alterations were observed in the level of GATA‑binding protein 6 (GATA6), Notch gene homolog 2 (NOTCH2), Wnt family member 5A (WNT5A), bone γ‑carboxyglutamate protein (BGLAP), chondroadherin (CHAD), dipeptidyl peptidase 4 (DPP4), ectonucleotide pyrophosphatase/phosphodiesterase 2 (ENPP2), alkaline phosphatase (ALP) 3 and ATPase phospholipid‑transporting 11A (ATP11A) in response to treatment with 0.1 µM 17‑β‑estradiol, 1 µM genistein, and/or 1 µM MK‑4. GATA6, NOTCH2 and WNT5A are considered to be associated with osteoclast, but not osteoblast, function; however, increases in osteoblastic mRNAs, including BGLAP and CHAD, were observed in each of the treatment groups at 48 h. Immunocytochemical analysis confirmed an increase in CHAD and DPP4 proteins following the administration of genistein + MK‑4. Furthermore, genistein + MK‑4 led to alterations in cell morphology to spindle or oval shapes, and increased the intensity of ALP staining. Although the level of ALP mRNA was not consistently altered in response to the treatments, a marked increase in ALP activity was observed following 96 h treatment with genistein + MK‑4. Therefore, the simultaneous intake of genistein and MK‑4 appears to be beneficial for the maintenance of bone quality.


Extremotolerance and resistance of lichens: comparative studies on five species used in astrobiological research I. Morphological and anatomical characteristics.
Lichens are symbioses of two organisms, a fungal mycobiont and a photoautotrophic photobiont. In nature, many lichens tolerate extreme environmental conditions and thus became valuable models in astrobiological research to fathom biological resistance towards non-terrestrial conditions; including space exposure, hypervelocity impact simulations as well as space and Martian parameter simulations. All studies demonstrated the high resistance towards non-terrestrial abiotic factors of selected extremotolerant lichens. Besides other adaptations, this study focuses on the morphological and anatomical traits by comparing five lichen species-Circinaria gyrosa, Rhizocarpon geographicum, Xanthoria elegans, Buellia frigida, Pleopsidium chlorophanum-used in present-day astrobiological research. Detailed investigation of thallus organization by microscopy methods allows to study the effect of morphology on lichen resistance and forms a basis for interpreting data of recent and future experiments. All investigated lichens reveal a common heteromerous thallus structure but diverging sets of morphological-anatomical traits, as intra-/extra-thalline mucilage matrices, cortices, algal arrangements, and hyphal strands. In B. frigida, R. geographicum, and X. elegans the combination of pigmented cortex, algal arrangement, and mucilage seems to enhance resistance, while subcortex and algal clustering seem to be crucial in C. gyrosa, as well as pigmented cortices and basal thallus protrusions in P. chlorophanum. Thus, generalizations on morphologically conferred resistance have to be avoided. Such differences might reflect the diverging evolutionary histories and are advantageous by adapting lichens to prevalent abiotic stressors. The peculiar lichen morphology demonstrates its remarkable stake in resisting extreme terrestrial conditions and may explain the high resistance of lichens found in astrobiological research.


Bone mineral content in Hawaiian, Asian, and Filipino children.
Os calcis bone mineral content (BMC) was measured by single photon absorptiometry in 86 children, ages 6 to 13 years from Hawaiian, Oriental, Caucasian, and Filipino ethnic groups. Pearson correlations indicated significant positive correlations between BMC and age, height, and weight. However, there were no significant differences in age, height or weight between ethnic groups. ANOVA revealed a significant effect of ethnic group on BMC with the Hawaiian group having a significantly higher BMC than the Asian or Caucasian groups. When age, height and weight were controlled for, ANCOVA still showed a significant effect of ethnicity on BMC. The current findings suggest that ethnic differences can develop early in life.


Nontuberculous mycobacteria isolation from sputum specimens: A retrospective analysis of 1061 cases.
In recent years, with the development of laboratory methods, the frequency of nontuberculosis mycobacteria (NTM) infections has increased. The primary aim of this study was to evaluate the clinical significance of therapeutic drug monitoring (TDM) growths in respiratory samples, and the secondary aim was to evaluate the treatment regimens and treatment outcomes of treatment for TDM disease. This study was a retrospective cohort study. Persons with NTM growth in respiratory samples admitted to the reference hospital between 2009 and 2020 were included in this study. Samples detected as NTM by the immunochromatographic rapid diagnostic test, those requested by the clinicians, species were determined by the hsp65PCRREA method. The subjects were classified into 3 groups: patients with NTM infection who received treatment (135, 12.7%), those followed up without treatment (690, 65.1%), and a last group of patients with Mycobacterium tuberculosis (TB) complex strains were isolated and received TB treatment (236, 22.2%). Initiating NTM treatment was decided in accordance with the American Thoracic Society recommendations. The mean ± standard deviation age of patients was 53.8 ± 16.5 years, and 749 (70.6%) were male. In total, 278 (26.2%) out of 1061 cases had identified, and the most frequent species were MAC (81; Mycobacterium avium: 39, Mycobacterium intracellulare: 39, and MAC: 3), Mycobacterium abscessus (67), Mycobacterium kansasii (48), Mycobacterium fortuitum (23), Mycobacterium chelonae (12), Mycobacterium gordonae (11), and Mycobacterium szulgai (11). In the NTM treatment group, 116 (85.9%) of 135 patients had multiple culture positivity. Previous TB treatment history had 51 (37.8%) of 135 patients, respiratory comorbidities were evident in 37 (27.4%) of 135 patients. Thorax computed tomography imaging in 84 patients revealed nodule 38 (45.2%), consolidation 46 (54.8%), cavity 52 (61.9%), and bronchiectasis 27 (32.1%). Treatment results in the NTM treatment group were as follows: ongoing treatment 14 (10.4%), cure 64 (47.4%), default 33 (24.4%), exitus 19 (14.1%), recurrence 3 (2.2%), and refractory disease 2 (1.5%). This is a large case series evaluating the clinical significance of NTM growths and NTM treatment in Turkey. The clinical significance of NTM growth in respiratory samples is low. Treatment success rates of NTM patients who are treated are low. Treatment defaults and mortality rates are high. New drugs and new regimens are needed.


Tissue Specific Fate of Nanomaterials by Advanced Analytical Imaging Techniques - A Review.
A variety of imaging and analytical methods have been developed to study nanoparticles in cells. Each has its benefits, limitations, and varying degrees of expense and difficulties in implementation. High-resolution analytical scanning transmission electron microscopy (HRSTEM) has the unique ability to image local cellular environments adjacent to a nanoparticle at near atomic resolution and apply analytical tools to these environments such as energy dispersive spectroscopy and electron energy loss spectroscopy. These tools can be used to analyze particle location, translocation and potential reformation, ion dispersion, and in vivo synthesis of second-generation nanoparticles. Such analyses can provide in depth understanding of tissue-particle interactions and effects that are caused by the environmental "invader" nanoparticles. Analytical imaging can also distinguish phases that form due to the transformation of "invader" nanoparticles in contrast to those that are triggered by a response mechanism, including the commonly observed iron biomineralization in the form of ferritin nanoparticles. The analyses can distinguish ion species, crystal phases, and valence of parent nanoparticles and reformed or in vivo synthesized phases throughout the tissue. This article will briefly review the plethora of methods that have been developed over the last 20 years with an emphasis on the state-of-the-art techniques used to image and analyze nanoparticles in cells and highlight the sample preparation necessary for biological thin section observation in a HRSTEM. Specific applications that provide visual and chemical mapping of the local cellular environments surrounding parent nanoparticles and second-generation phases are demonstrated, which will help to identify novel nanoparticle-produced adverse effects and their associated mechanisms.


Patterns of oral care in dental school and general dental practice.
This study compared patterns of oral care provided by predoctoral dental students for patients seeking treatment at the University of Washington (UW) with patterns reported for general dental offices by the Washington Dental Service (WDS). Dental care included about 5 million services provided to 880,317 patients by 2,803 WDS general dentists and about 45,600 dental services provided to 9,488 patients by 155 UW dental students during 1999. There was high fidelity between databases and randomly surveyed patient records for treatment provided in both UW (95 percent) and WDS (97 percent) populations. While patient age patterns were generally similar, UW students completed more procedures for young children and for adults older than seventy-four years but completed fewer procedures for age groups of from thirteen to eighteen and from forty-five to fifty-four than general dental offices. The relative mix of all services completed by UW and WDS providers was similar (ANOVA, P=0.82). Within categories of service, the percentage of total services completed by students compared to those submitted by community dentists to WDS was about the same for examinations, radiographs, fluoride and sealants, amalgams, composites, single crowns, and endodontics. The percentage of total procedures completed showed a greater emphasis by UW students on inlays/onlays, dentures, extractions, and periodontal maintenance, and lesser experience with implants, orthodontics, sedation, and emergency procedures than general dental offices. We conclude that the relative distribution of clinical services provided by UW dental students is comparable to those procedures reported to WDS by dental offices in the adjacent community.


Decoding overt shifts of attention in depth through pupillary and cortical frequency tagging.
Objective. We have recently developed a prototype of a novel human-computer interface for assistive communication based on voluntary shifts of attention (gaze) from a far target to a near target associated with a decrease of pupil size (Pupillary Accommodative Response, PAR), an automatic vegetative response that can be easily recorded. We report here an extension of that approach based on pupillary and cortical frequency tagging.Approach. In 18 healthy volunteers, we investigated the possibility of decoding attention shifts in depth by exploiting the evoked oscillatory responses of the pupil (Pupillary Oscillatory Response, POR, recorded through a low-cost device) and visual cortex (Steady-State Visual Evoked Potentials, SSVEP, recorded from 4 scalp electrodes). With a simple binary communication protocol (focusing on a far target meaning 'No', focusing on the near target meaning 'Yes'), we aimed at discriminating when observer's overt attention (gaze) shifted from the far to the near target, which were flickering at different frequencies.Main results. By applying a binary linear classifier (Support Vector Machine, SVM, with leave-one-out cross validation) to POR and SSVEP signals, we found that, with only twenty trials and no subjects' behavioural training, the offline median decoding accuracy was 75% and 80% with POR and SSVEP signals, respectively. When the two signals were combined together, accuracy reached 83%. The number of observers for whom accuracy was higher than 70% was 11/18, 12/18 and 14/18 with POR, SVVEP and combined features, respectively. A signal detection analysis confirmed these results.Significance. The present findings suggest that exploiting frequency tagging with pupillary or cortical responses during an attention shift in the depth plane, either separately or combined together, is a promising approach to realize a device for communicating with Complete Locked-In Syndrome (CLIS) patients when oculomotor control is unreliable and traditional assistive communication, even based on PAR, is unsuccessful.


Does a Decade of School Administrator Support for Educator Training on Students' Sexual and Gender Identity Make a Difference for Students' Victimization and Perceptions of School Climate?
Professional development training for school personnel on issues related to sexual and gender identity (i.e., SOGI training) is a school strategy designed to prevent health and educational disparities for lesbian, gay, bisexual, and transgender (LGBT) youth at school. Yet we know surprisingly little about how the presence of this practice at school affects students' experience. This study explores whether students' experiences of victimization and school climate vary as a function of school administrator support for SOGI training at two time points (2004 and 2014). We combined multiple independent databases: students' reports on victimization and school climate in 2013-2015 (n = 55,158), and school (n = 152) and school district data (n = 67) on support for SOGI training in 2004 and 2014. More positive school climates were found in schools with support for SOGI training in 2004 only and both 2004 and 2014 compared to schools with SOGI training support in 2014 only. In schools with support for SOGI training in both 2004 and 2014, LGBT students reported the lowest rates of victimization. Findings from this study provide evidence that support for SOGI training by school administration is an effective way to improve school contexts for LGBT and all students. School administrators who aim to reduce victimization disparities for LGBT students and improve school climates should support the implementation of SOGI training, and sustain such training over time.


Genistein modulates oxidative stress in breast cancer cell lines according to ERα/ERβ ratio: effects on mitochondrial functionality, sirtuins, uncoupling protein 2 and antioxidant enzymes.
Genistein is a biologically active isoflavone with estrogenic activity and can be found in a variety of soy products. This natural compound displays a wide array of biological activities, but it is best known for its ability to inhibit cancer progression, especially for hormone-related ones such as breast cancer. Genistein has been shown to bind both the estrogen receptor alpha (ERα) and the estrogen receptor beta (ERβ), although it has a higher affinity for the ERβ. The ERα/ERβ ratio is a prognostic marker for breast tumors, and ERβ expression could indicate the presence of tumors more benign in state, whereas ERα indicates malignant tumors. The objective of the present study was to investigate the effects of genistein on oxidative stress and mitochondrial functionality through its interaction with the estrogen receptor in breast cancer cell lines with different ERα/ERβ ratios. The lower ERα/ERβ ratio T47D cell line showed lower oxidative stress and greater mitochondrial functionality, along with an up-regulation of uncoupling protein 2 and sirtuins. On the other hand, genistein-treated MCF-7 cell line, with the highest ERα/ERβ ratio, reported no changes for the control situation. On the whole, our results show different genistein effects depending on ERα/ERβ ratio for oxidative stress regulation, mitochondrial functionality, and modulation of UCPs, antioxidant enzymes and sirtuins in breast cancer cell lines. Effects of genistein on oxidative stress and mitochondria could be due at least in part, to a higher ERβ presence, but could also be due to up-regulation of ERβ caused by the genistein treatment.


Administering the contract.
Administering the collective bargaining contract is a challenging and important nursing administration responsibility. This article discusses the attitudes, skills, and strategies that the nursing administrator who manages a unionized professional staff can use to minimize employee grievances and foster a professional practice climate. Directors of nursing in nonunionized settings also can use these guidelines to maintain the union-free status of their departments.


Psychiatric care and home care service - an exploration of the professional world encountered by persons with long-term mental illness.
Psychiatric care and home care service - an exploration of the professional world encountered by persons with long-term mental illness This study focuses on the views of professional health care providers within a geographical district in Sweden. A total of 52 interviews with persons representing different professional levels within psychiatry and the social services were conducted. The purpose was to compare their understanding of what their responsibility entailed as well as their perceptions of goals and required competence. A content analysis, supplemented with interpretations within a hermeneutic tradition, showed that there are both similarities and differences within and between the two organizations. A common finding is that professionals with the least education are to a great extent responsible for the practical care of persons with long-term mental illness. The implication of this finding is that it is important to be aware of this division of responsibility when developing psychiatric nursing and the home care services according to the needs of long-term mentally ill patients.


Eumycetoma Osteomyelitis of the Calcaneus in a Child: A Radiologic-Pathologic Correlation following Total Calcanectomy.
Fungi are unusual causes of pedal osteomyelitis in children and adolescents. Eumycetoma is a chronic cutaneous and subcutaneous infection caused by various genera of fungi. A provisional diagnosis of foot mycetoma is made after clinical assessment. Radiologic-pathologic correlation is an essential supplement for the accurate diagnosis of osteoarticular infections. This paper aims to sensitize orthopedic surgeons, radiologists, and pathologists to the importance of correlative imaging findings in relation to surgical and microscopic pathology in osteoarticular infections, specifically eumycetoma osteomyelitis of the foot. From our review of the published data, the present case is the first report of radiologic-pathologic correlation in eumycetoma osteomyelitis of the calcaneus. This paper describes a case of eumycetoma osteomyelitis of the calcaneus in a child in which diagnostic X-rays and magnetic resonance imaging (MRI) were correlated with the surgical and microscopic pathologic features, for establishing an appropriate diagnosis and treatment. We conclude that there is a significant agreement between radiologic and pathologic evaluation for assessment of eumycetoma osteomyelitis of the calcaneus. Radiologic-pathologic correlation amplified our interpretation of imaging information available on plain radiographs and MRI and augmented diagnostic confidence. Similarly, anatomic-histopathological correlations consolidated diagnostic accuracy.


The dietary protein/carbohydrate ratio differentially modifies lipogenesis and protein synthesis in the mammary gland, liver and adipose tissue during gestation and lactation.
During gestation and lactation, a series of metabolic changes that are affected by the diet occurs in various organs of the mother. However, little is known about how the dietary protein (DP)/carbohydrate (DCH) ratio regulates the expression of metabolic genes in the mother. Therefore, the purpose of this work was to study the effect of consuming different percentages of DP/DCH, specifically 10/73, 20/63 and 30/53%, on the expression of genes involved in lipogenesis and protein synthesis in the mammary gland, liver and adipose tissue during gestation and lactation in dams. While the amount of weight gained during gestation was similar for all groups, only dams fed with 30/53% DP/DCH maintained their weight during lactation. In the mammary gland, the expression of the genes involved in lipogenesis, specifically SREBP1 and FAS, was dramatically increased, and the expression of the genes involved in protein synthesis, such as mTOR1, and the phosphorylation of its target protein, S6K, were also increased throughout pregnancy and lactation, regardless of the concentration of DP/DCH. In the liver and adipose tissue, the expression of the genes and proteins involved in lipid metabolism was dependent on the proportion of DP/DCH. The consumption of a low-protein/high-carbohydrate diet increased the expression of lipogenic genes in the liver and adipose tissue and the amount of lipid deposition in the liver. Conversely, the consumption of a high-protein/low-carbohydrate diet increased the expression of genes involved in amino acid oxidation in the liver during gestation. The metabolic adaptations reflected by the changes in the expression of metabolic genes indicate that the mammary gland has a priority for milk synthesis, whereas the adaptations in the liver and adipose tissue are responsible for providing nutrients to the mammary gland to sustain milk synthesis.


A behavioral homeostasis theory of habituation and sensitization: II. Further developments and predictions.
Habituation may be viewed as a decremental behavioral change to iterative stimuli of little immediate relevance. It is observed from protozoa to humans, indicating its evolutionary significance. If habituation is interpreted as the process of filtering out unimportant repetitive stimuli, then how should sensitization be interpreted? The 'behavioral homeostasis theory' of these two behaviors is based on the notion that organisms at a high level of 'alertness' prior to experiencing a new iterative stimulus will show a large initial response followed by a decrement (habituation) if the stimulus is of little significance. Conversely, the same organism at a low level of 'alertness' will show a small initial response to the same stimulus followed by an increase in 'alertness' and a larger response to the next stimulus (sensitization) in order to receive enough information to assess its significance. Circadian rhythmicity is hypothesized to play a role in determining 'alertness' to a new iterative stimulus at any given time. The level of responsiveness in initial habituaters and sensitizers, as an asymptote is approached, is a balance between being too 'alert' to an unimportant stimulus and missing other significant stimuli, and being too 'un-alert' and missing a change in the relevance of the present iterative stimulus. The concept of 'behavioral homeostasis' includes behaviors beyond habituation and sensitization across phylogeny. It includes instinctive as well as learned, and group as well as individual behavior. Such behavioral homeostatic processes to optimize detection and assessment of constantly occurring external stimuli are critical for organism survival. Clinical implications of this theory are also examined.


Effect of normal and activated human macrophages on Toxoplasma gondii.
Human macrophages derived from in vitro culture of peripheral blood monocytes were studied under a variety of conditions to determine their microbicidal capacity for the obligate intracellular protozoan, Toxoplasma gondii. The effect of macrophages on intracellular Toxoplasma was evaluated morphologically by light and phase microscopy and by autoradiography. When macrophages from dye test (DT)-negative or DT-positive individuals were infected with Toxoplasma in the presence of normal human serum, the organisms were able to multiply intracellularly with resultant destruction of the monolayer. Once organisms were intracellular, the presence of antibody-containing serum in the medium did not alter this inability of the macrophages to kill Toxoplasma. However, when Toxoplasma were incubated in the presence of heat-inactivated DT-positive serum just before infection of the monolayers, the intracellular organisms were inhibited or killed by normal macrophages. Attempts were made to activate macrophages in vitro to kill Toxoplasma. Macrophages incubated in the presence of sensitized lymphocytes and Streptokinase-Streptodornase (SK-SD) or Toxoplasma lysate antigen (TLA) were found to kill Toxoplasma when compared to macrophages incubated in the presence of lymphocytes from DT-negative individuals and TLA or lymphocytes alone. Thus, in vitro induction of resistance (both specifically and nonspecifically) in human macrophages was accomplished by culturing these cells in the presence of specifically sensitized lymphocytes and antigen. These results suggest that, as in the mouse model, activated human macrophages have the ability to inhibit or kill intracellular Toxoplasma and that these cells may be important as effector cells in cell-mediated immunity (CMI) to toxoplasmosis in man.


A transformative mission for prioritising nature in Australian cities.
Australia is experiencing mounting pressures related to processes of urbanisation, biodiversity loss and climate change felt at large in cities. At the same time, it is cities that can take the leading role in pioneering approaches and solutions to respond to those coupling emergencies. In this perspective piece we respond to the following question: What are the required transformations for prioritising, valuing, maintaining and embracing nature in cities in Australia? We adopt the mission framework as an organising framework to present proposed pathways to transform Australian cities as nature-positive places of the future. We propose three interconnected pathways as starting actions to steer urban planning, policy and governance in Australian cities: First, cities need to establish evidence-based planning for nature in cities and mainstream new planning tools that safeguard and foreground urban nature. Second, collaborative planning needs to become a standard practice in cities and inclusive governance for nature in cities needs to prioritise Aboriginal knowledge systems and practices as well as look beyond what local governments can do. Third, for progressing to nature-positive cities, it is paramount to empower communities to innovate with nature across Australian cities. Whilst we focus on Australian cities, the lessons and pathways are broadly applicably globally and can inspire science-policy debates for the post COP15 biodiversity and COP26 climate change implementation processes.


Effects of Thyroid Stimulating Hormone (TSH) level on clinical pregnancy rate via In Vitro Fertilization (IVF) procedure.
Subclinical hypothyroidism may adversely affect In Vitro Fertilization (IVF) outcomes. However the cutoff of thyroid-stimulating hormone (TSH) for diagnosis and treatment is controversal. The aim of this study was to find the association of clinical pregnancy rate with regard to TSH levels in women undergoing IVF. A historical cohort study of 816 infertile patients who underwent IVF in 2011 and 2012 was conducted. The study subjects were categorized in two groups according to their baseline TSH level; one with 0.5 ≤TSH< 2.5 mIU/L and other with 2.5 ≤TSH< 4.5 mIU/L. All patients were followed up for 6 weeks after embroyonic transfer. The outcomes of the study were consisted of rates for Human Chorionic Gonadotropin (HCG) and evaluation of their clinical pregnancies. About 60% of the study subjects had serum TSH level < 2.5 mIU/L and 40% ≥ 2.5 mIU/L. There were no statistically significant differences in age, years of infertility, BMI, baseline FSH and estradiol level of patients and the type of induction protocols between the study groups. The HCG rise was occurred in 30.4% of the subjects with TSH level < 2.5 mIU/L versus 26.3% of the subjects with TSH ≥ 2.5 mIU/L (p value= 0.2). The clinical pregnancy rates in the group of patients with TSH < 2.5 mIU/L and those with ≥ 2.5 mIU/L were 27.1% and 23.9% respectively (p value= 0.3). Our results were similar to various studies in which reported lack of association between TSH level in the range of 0.5- 4.5 mIU/L and IVF outcomes. It seems that lowering the upper limit of normal TSH should be still considered as a scientific debate.


Comparison of recombinant and purified human bone morphogenetic protein.
Clinically, it would be more convenient to use recombinant than purified preparations of bone morphogenetic protein (BMP). Recently, recombinant human BMP (rhBMP) has attracted the attention of many investigators, but it has not been fully characterized. We examined the bone-inducing activity of rhBMP-2 and compared it with that of purified BMP derived from human bone matrix (phBMP). Two, 10, or 50 microg of rhBMP-2 or phBMP was mixed with 3 mg of atelopeptide type I collagen (carrier), and specimens were implanted in the calf muscles of Wistar rats (n=5 in each group). Four weeks later, new bone had formed in all the rhBMP-2- and phBMP-implanted muscles and was visible radiographically and histologically. The quantitative analysis indicated that the activity of rhBMP-2 was less than one tenth that of phBMP. It is necessary to find out why rhBMP-2 has fewer activities than phBMP.


The Development and Validation of a Predictive Model for Voriconazole-Related Liver Injury in Hospitalized Patients in China.
Voriconazole is widely used in the treatment and prevention of invasive fungal diseases. Common drug-induced liver injuries increase the economic burdens and the risks of premature drug withdrawal and disease recurrence. This study estimated the disposal cost of voriconazole-related liver injury, explored the risk factors of voriconazole-related liver injury in hospitalized patients, and established a predictive model of liver injury to assist clinicians and pharmacists in estimating the probability or risk of liver injury after voriconazole administration to allow for early identification and intervention in patients at high risk of liver injury. A retrospective study was conducted on the selected inpatients whose blood concentration of voriconazole was measured in the West China Hospital of Sichuan University from September 2016 to June 2020. The incidence and disposal cost of voriconazole-related liver injuries were calculated. The incidence of voriconazole-related liver injury was 15.82% (217/1372). The disposal cost has been converted to 2023 at a discount rate of 5%. The median (P25, P75) disposal cost of severe liver injury (n = 42), general liver injury (n = 175), and non-liver injury (n = 1155) was 993.59 (361.70, 1451.76) Chinese yuan, 0.00 (0.00, 410.48) yuan, and 0.00 (0.00, 0.00) yuan, respectively, with a statistically significant difference (p < 0.001). Single factor analysis and multiple factor logistic regression were used to analyze the risk factors of voriconazole-related liver injury. The voriconazole-related liver injury was related to the trough concentration (Cmin, OR 1.099, 95% CI 1.058-1.140), hypoproteinemia (OR 1.723, 95% CI 1.126-2.636), and transplantation status (OR 0.555, 95% CI 0.325-0.948). The prediction model of liver injury was Logit (P)= -2.219 + 0.094 × Cmin + 0.544 × Hydroproteinemia - 0.589 × Transplantation, and the prediction model nomogram was established. The model validation results showed that the C-index of the derivation set and validation set was 0.706 and 0.733, respectively. The area under the curve (AUC) of the receiver operating characteristic (ROC) curve was 0.705 and 0.733, respectively, indicating that the model had good prediction ability. The prediction model will be helpful to develop clinical individualized medication of voriconazole and to identify and intervene in the cases of patients at high risk of voriconazole-related liver injury early on, in order to reduce the incidence of voriconazole-related liver injuries and the cost of treatment.


Levonorgestrel-releasing intrauterine system (Mirena) in compare to medroxyprogesterone acetate as a therapy for endometrial hyperplasia.
This study was designed to evaluate the comparison of insertion of levonorgestrel (LNG)-releasing intrauterine system versus oral medroxyprogesterone acetate on endometrial hyperplasia in a randomized controlled trial. A total of 60 women with the initial histopathological diagnosis of endometrial hyperplasia in two groups received LNG or medroxyprogesterone (10 mg/d orally) for 12 days a month for 3 months). Endometrial biopsy was obtained for all patients after 3 months of treatment. Response to treatment was defined based on the histopathology of the post treatment pipelle endometrial specimens in three categories of resolution, persistence and progression. Treatment response rate in patients in the LNG group was 89.3% (25 of 28 patients), versus 70.4% (19 of 27 patients) in patients in the medroxyprogesterone group. The rate of persistence was 10.7% (3 of 28 patients) and 22.2% (6 of 27 patients) in LNG and medroxyprogesterone groups respectively. No progression of endometrial hyperplasia observed in any of the patients in LNG group, but progression of endometrial hyperplasia was observed in 7.4% (2 of 27 patients) in the medroxyprogesterone group. There was no statistically significant difference between groups regarding the response to treatment (P = 0.15). Side effects such as bloating, weight gain, fatigue and hair loss were comparable between the groups (P > 0.05). Hirsutism was significantly more in the medroxyprogesterone group than LNG group (P = 0.013). Results showed that the use of LNG for treating endometrial hyperplasia for 3 months was associated with high-treatment response rate and the low proportion of patients with progression compared to the use of medroxyprogesterone.


[Degradation of halogenated compounds by haloalkane dehalogenase DadA from Alcanivorax dieselolei B-5 ].
[OBJECTIVE] Alcanivorax dieselolei B-5 is an important oil-degrading bacterium. We studied its substrate range and degradation of halogenated compounds. [METHODS] Growth capability of B-5 was examined with different halogenated substrates as sole carbon source. A putative haloalkane dehalogenase (HLD) gene named dadA was found from the genome of strain B-5 and analyzed by sequence alignment, phylogenetic analysis and homologous modeling. After heterologous expression in Escherichia coli and purification, the activity of DadA towards 46 substrates was determined. [RESULTS] Strain B-5 was capable of utilizing various halogenated compounds (C3-C,8) as the sole carbon source. DadA had typical catalytic pentad residues of HLD-II subfamily, but it was independent from other members of this subfamily according to phylogenetic analysis. Activity assay showed that DadA has higher specificity and narrower substrate range than other characterized HLDs and it only showed activity toward 1,2,3-tribromopropane, 1,2-dibromo-3-chloropropane and 2,3-dichloroprop-1-ene among 46 tested substrates. [CONCLUSIONS] Strain B-5 and its HLD DadA can degrade halogenated aliphatic pollutants although.


Matrix remodeling in the ovary: regulation and functional role of the plasminogen activator and matrix metalloproteinase systems.
In each reproductive cycle, extensive tissue remodeling takes place in the ovary during follicular development, ovulation, formation and regression of corpus luteum (CL) and follicular atresia. Several lines of indirect evidence suggest that these changes are mediated, in part, by proteases belonging to the plasminogen activator (PA) and the matrix metalloproteinase (MMP) systems. These two enzyme systems include both proteinases and associated inhibitors, that are thought to act in concert via a cascade of proteolytic events, the end result of which is the generation of a broad spectrum proteolytic activity, that can mediate physiological tissue remodeling throughout the body. The current review highlights the key features of these two enzyme systems and focuses on their regulation and functional role during the dynamic remodeling processes that takes place in the ovary during each reproductive cycle.


Mid-infrared sensing of molecular vibrational modes with tunable graphene plasmons.
We study the tunable plasmons based on a graphene integrated gold grating structure to sense the vibrational modes of nanometric molecules. The greatly enhanced light-matter interaction and the broadband tunability of the localized graphene plasmonic resonance enable accurate label-free identification of the molecular vibrational modes at subwavelength scale. Our results may accelerate the further development of novel cost-effective biosensors with superior molecular chemical fingerprint sensitivity in an active graphene plasmonic device.


[Comprehensive geriatric assessment in older patients with diabetes mellitus].
Because the prevalence of older old patients with diabetes is increasing in Japan, diabetic patients with physical or cognitive impairment are also becoming to be more prevalent in clinical practice. The comprehensive geriatric assessment (CGA) consists of 5 important domains: physical function (basic ADL, instrumental ADL, vision, etc.), psychological function, mental function, socio-economic conditions, and patient's preference. The functions in CGA can be used as predictors for prognosis, a tool for early diagnosis of dementia, assessment tool of patient's capacity for insulin self-injection, and outcomes of diabetes treatment. The CGA is also useful in performing a patient-centered approach to improve the physical, psychological, and mental functions as well as to individualize a treatment goal of HbA1c in elderly patients with diabetes mellitus.


Assessing regulatory information in developmental gene regulatory networks.
Gene regulatory networks (GRNs) provide a transformation function between the static genomic sequence and the primary spatial specification processes operating development. The regulatory information encompassed in developmental GRNs thus goes far beyond the control of individual genes. We here address regulatory information at different levels of network organization, from single node to subcircuit to large-scale GRNs and discuss how regulatory design features such as network architecture, hierarchical organization, and cis-regulatory logic contribute to the developmental function of network circuits. Using specific subcircuits from the sea urchin endomesoderm GRN, for which both circuit design and biological function have been described, we evaluate by Boolean modeling and in silico perturbations the import of given circuit features on developmental function. The examples include subcircuits encoding positive feedback, mutual repression, and coherent feedforward, as well as signaling interaction circuitry. Within the hierarchy of the endomesoderm GRN, these subcircuits are organized in an intertwined and overlapping manner. Thus, we begin to see how regulatory information encoded at individual nodes is integrated at all levels of network organization to control developmental process.


Estimation of fetal weighty by ultrasonic abdominometry.
The fetal abdomen was measured with an ultrasonic contact scanner in order to correlate abdomenal circumference and birth weight. A sample of 134 measurements was used to calculate a standard graph, which was then tested against a subsequent 280 measurements, giving a mean estimation error of 105 Gm. Head-to-abdomen circumference ratio measurements were used to assess the type of growth retardation.


[Aneurysms of the celiac artery: case report and review of the literature].
Aneurysm of the celiac trunk is uncommun, accounting for 6% of all splanchnic artery aneurysms. Atherosclerosis is the main cause, other causes include fibrodysplasia and more rarely mycotic or post-stenotic conditions. Usually asymptomatic, detection is generally fortuitous. Ultrasound, angiography and CT scan provide the positive diagnosis. Rupture is the most serious complication. The risk is about 13% per year with high mortality (80%). Cure can be achieved by conventional or endovascular surgery. We report an aneurysm of the bifurcation of the celiac trunk in a 70-year-old woman. Diagnosis was fortuitous. The aneurysm was sacciform with a 2.5 cm diameter and a large collar. Because of its locations and shape, no endovascular procedure could be attemped. Reconstruction with a patch was achieved with conventional surgery. The post-operative period was uneventful. Ultrasound at 3, 6, 12 and 36 months showed a normal caliber with regular blood flow in the reconstructed vessels.


Structure of the asparagine-linked sugar chains of alpha-fetoprotein purified from human ascites fluid.
alpha-Fetoprotein purified from human serum was found to contain an asparagine-linked sugar chain in one molecule. The sugar chain was quantitatively released from the polypeptide moiety by hydrazinolysis and recovered as oligosaccharides after N-acetylation. The oligosaccharide mixture was separated into a neutral (N) and two acidic (A-1 and A-2) fractions by paper electrophoresis. By combination of sequential exoglycosidase digestion, methylation analysis, and concanavalin A-Sepharose column chromatography, the structures of these fractions were determined to be: Gal beta 1 leads to 4GlcNAc beta 1 leads to 2Man alpha 1 leads to 6(Gal beta 1 leads to 4GlcNAc beta 1 leads to 2Man alpha 1 leads to 3)Man beta 1 leads to 4GLcNAc beta 1 leads to 4(+/- Fuc alpha 1 leads to 6)GlcNAc; Gal beta 1 leads to 4GlcNAc beta 1 leads to 2Man alpha 1 leads to 6(NeuAc alpha 2 leads to 6Gal beta 1 leads to 4GlcNAc beta 1 leads to 2Man alpha 1 leads to 3)Man beta 1 leads to 4GlcNAc beta 1 leads to 4(+/- Fuc alpha 1 leads to 6(GlcNAc; and NeuAc alpha 2 leads to 6Gal beta 1 leads to 4GlcNAc beta 1 leads to 2Man alpha 1 leads to 6(NeuAc alpha 2 leads to 6Gal beta 1 leads to 4GlcNAc beta 1 leads to 2Man alpha 1 leads to 3)Man beta 1 leads to 4GlcNAc beta 1 leads to 4(+/- Fuc alpha 1 leads to 6)GlcNAc.


Mercury compounds reduce photosynthesis by plankton.
Concentrations of organomercurial fungicides as low as 0.1 part per billion in water reduced photosynthesis and growth in laboratory cultures of one species of marine diatom and several natural phytoplankton communities from Florida lakes. The acute toxicity of mercury compounds to phytoplankton is dependent on the chemical nature of the mercury compound and on cell concentrations.


Characterisation of the cell line HC-AFW1 derived from a pediatric hepatocellular carcinoma.
Current treatment of paediatric hepatocellular carcinoma (HCC) is often inefficient due to advanced disease at diagnosis and resistance to common drugs. The aim of this study was to generate a cell line derived from a paediatric HCC in order to expand research in this field. We established the HC-AFW1 cell line from a liver neoplasm of a 4-year-old boy through culturing of primary tumor specimens. The cell line has been stable for over one year of culturing and has a doubling time of 40 h. The tumour cells have an epithelial histology and express HCC-associated proteins such as Alpha-fetoprotein (AFP), Glypican 3, E-cadherin, CD10, CD326, HepPar1 and Vimentin. Forty-nine amino acids in exon 3 of β-Catenin that involve the phosphorylation sites of GSK3 were absent and β-Catenin is detectable in the cell nuclei. Cytogenetic analysis revealed large anomalies in the chromosomal map. Several alterations of gene copy numbers were detected by genome-wide SNP array. Among the different drugs tested, cisplatin and irinotecan showed effective inhibition of tumour cell growth in a proliferation assay at concentrations below 5 µg/ml. Subcutaneous xenotransplantation of HC-AFW1 cells into NOD/SCID mice resulted in fast growing dedifferentiated tumours with high levels of serum AFP. Histological analyses of the primary tumour and xenografts included national and international expert pathological review. Consensus reading characterised the primary tumour and the HC-AFW1-derived tumours as HCC. HC-AFW1 is the first cell line derived from a paediatric HCC without a background of viral hepatitis or cirrhosis and represents a valuable tool for investigating the biology of and therapeutic strategies for childhood HCC.


Is lithium monitoring NICE? Lithium monitoring in a UK secondary care setting.
Lithium is widely used for the treatment of bipolar disorder. Owing to its narrow therapeutic index and side-effect profile, regular monitoring of serum levels, renal and thyroid function has been recommended by all major guidelines on lithium use. We investigated whether lithium monitoring during maintenance phase treatment in clinical practice meets the latest recommendation by the National Institute for Health and Clinical excellence (i.e. lithium levels between 0.6 and 1.0 mmol/L and lithium level, thyroid and renal function tests every 6 months) in one of the largest mental health organizations in Europe, the South London and Maudsley (SLaM) NHS Foundation Trust. Retrospective data were extracted from SLaM's Clinical Record Interactive Search (CRIS) system. Adult patients with a psychiatric disorder who were on lithium at any point during the period January 2012-January 2016 and had at least one lithium level test result in the system were included in the analyses. A total of 2639 lithium level tests results were retrieved for 412 patients. Overall, the serum level was within the recommended range in 50.7% of all tests, below the range in 42.4% and above in 6.9%. Lithium level, renal and thyroid function tests were performed at the recommended frequency of 6 months (or less) in 76.2%, 72.7% and 60.2% of patients, respectively. These data demonstrate that there is a gap between the NICE 2014 recommendation and lithium monitoring practice in secondary care, with a high number of lithium level results below the therapeutic minimum. Reminder strategies for secondary care practitioners, shared care agreements or a central registry for lithium users could improve monitoring performance.


Effect of various concentrations of prolactin and growth hormone on the magnitude of stimulation of RNA synthesis, casein synthesis and ornithine decarboxylase activity in mouse mammary gland explants.
The effects of various concentrations of prolactin and growth hormone on the rates of [3H]-uridine incorporation into RNA, [3H]-leucine incorporation into casein, and ornithine decarboxylase (ODC) activity were determined in mouse mammary gland explants. The lowest concentrations of prolactin which produced significant responses were between 5 and 25 ng/ml. Growth hormone, in contrast, produced significant response at concentrations between 250 and 1,000 ng/ml. The prolactin actions on RNA and casein synthesis were essentially all-or-none type responses, i.e. the magnitude of the responses were maximal at about 10 ng/ml prolactin. The action of prolactin on ODC activity was quite different; a concentration-response relationship was observed with prolactin at concentrations from 10 t 250 ng/ml. It is apparent from these studies that different concentrations of prolactin are required to produce optimal actions on different biochemical parameters in cultured mammary tissues.


[Motility effects of methamphetamine in morphine-tolerant mice by the DAP method].
We reported that the reverse tolerance to the effect of morphine on ambulatory activity did not develop in mice treated with morphine-admixed food. In this study, effects of repeated administration of methamphetamine on ambulatory activity were studied in mice treated with morphine-admixed food. The ambulatory activity was determined by the tilting cage method. Methamphetamine injection (1 mg/kg, s.c.) was repeated at 3 approximately 4 day intervals. The ambulatory activity was enhanced progressively when methamphetamine was repeatedly given in mice. However, the enhancing effect was not observed in mice treated with morphine-admixed food (1 mg/g food). Moreover, in a single injection experiment, the effect of the combination of methamphetamine and morphine on ambulatory activity was more potent than that of each drug. These results suggested that the reverse tolerance to methamphetamine did not develop under the condition of exposure to morphine by the DAF (drug-admixed food) method, and the developmental mechanism of reverse tolerance to methamphetamine might be similar to that of morphine.


Effects of the craniocervical flexion and isometric neck exercise compared in patients with chronic neck pain: A randomized controlled trial.
The present study compared the effects of neck isometric exercise (NIE) and craniocervical flexion exercise (CFE) on cervical lordosis, muscle endurance of cervical flexion, neck disability index (NDI), and active cervical range of motion (ACROM) in all three planes in patients with non-specific, chronic neck pain (CNP). Forty-one patients from a university hospital-based rehabilitation center were randomly assigned to an experimental (22 patients performing CFE) or control (19 patients performing NIE) group. All patients performed three 30-second repetitions of stretching exercises for the neck flexor, extensor, lateral flexor, and rotator as warm-up and cool-down exercises. The patients in the experimental group then underwent CFE 30 minutes/day, 3 times a week, for 8 weeks, while the control group underwent NIE. The main outcome measures were pain on visual analogue scale (VAS) and perceived disability based on the neck disability index (NDI). The secondary outcomes were cervical lordosis measured by an absolute rotation angle (ARA), muscle endurance of cervical flexion, and ACROM. Both groups showed improved pain, NDI, endurance of the cervical flexor muscles, and ACROM in all three planes after 8 weeks (p < 0.001 for all). All these outcomes, except for the NDI, showed significantly greater improvements following CFE than following NIE (p < 0.05 for all). In particular, a significantly improved ARA of cervical lordosis was found following CFE but not following NIE (p < 0.05). CFE targeted at retraining the craniocervical flexor muscles was useful for improving or restoring the pain, cervical lordosis, and neck-related function disorders among patients with non-specific CNP.


Preparedness for the Rio 2016 Olympic Games: hospital treatment capacity in georeferenced areas.
Recently, Brazil has hosted mass events with recognized international relevance. The 2014 FIFA World Cup was held in 12 Brazilian state capitals and health sector preparedness drew on the history of other World Cups and Brazil's own experience with the 2013 FIFA Confederations Cup. The current article aims to analyze the treatment capacity of hospital facilities in georeferenced areas for sports events in the 2016 Olympic Games in the city of Rio de Janeiro, based on a model built drawing on references from the literature. Source of data were Brazilian health databases and the Rio 2016 website. Sports venues for the Olympic Games and surrounding hospitals in a 10km radius were located by geoprocessing and designated a "health area" referring to the probable inflow of persons to be treated in case of hospital referral. Six different factors were used to calculate needs for surge and one was used to calculate needs in case of disasters (20/1,000). Hospital treatment capacity is defined by the coincidence of beds and life support equipment, namely the number of cardiac monitors (electrocardiographs) and ventilators in each hospital unit. Maracanã followed by the Olympic Stadium (Engenhão) and the Sambódromo would have the highest single demand for hospitalizations (1,572, 1,200 and 600, respectively). Hospital treatment capacity proved capable of accommodating surges, but insufficient in cases of mass casualties. In mass events most treatments involve easy clinical management, it is expected that the current capacity will not have negative consequences for participants.


The precise human bioclock, possibly imported.
Contrary to what has long been suggested, the biological clock is not a poor timekeeper. In fact, it has been working in precision for millions of years as a genetically set clock, independent of environmental periodicity. However, as the Earth's rotation has gradually slowed, this internal clock has gone through a relative phase shift. Extrapolating of changes backwards through time shows that the clock was set when mammals first appeared on the planet. Interestingly, primates are the only beings that have a free-running cycle longer than 24 hours. This bioclock may be set by lunar entrainment, or may be set extraterrestrially?


Significance of NOTCH1 Expression in the Progression of Human Lung and Colorectal Cancers.
Lung and colorectal cancers are the most common types of cancer characterized by a poor prognosis and a high mortality rate. Mutations in the genes encoding components of the main intra- and extracellular signaling pathways, in particular the NOTCH1 gene (Notch1, a member of the Notch family of receptors), play one of the key roles in progression of these malignancies. Notch signaling is involved in maintaining homeostasis of the intestinal epithelium and structural and functional lung elements. Therefore, it is not surprising that the constitutive activity and hyperactivity of Notch signaling due to somatic mutations in genes coding for the products directly involved into its activation, could lead to the progression of these cancer types. The aim of our study was to investigate how the NOTCH1 downregulation via RNA interference (RNAi) affects the phenotype, characteristics, and Notch-dependent signaling of human A549 lung and HCT116 colorectal carcinoma cells. Several small harpin RNAs (shRNAs) were selected using the bioinformatic analysis and tested for their ability to suppress the NOTCH1 expression. The most efficient one was used to produce the A549 and HCT116 cells with NOTCH1 knockdown. The obtained cell lines demonstrated decreased proliferation rates, reduced colony-forming capacity under adhesive conditions, and decreased migration activity in a Boyden chamber. The NOTCH1 knockdown also significantly decreased expression of some Notch signaling target genes potentially involved in the acquisition and maintenance of more invasive and malignant cell phenotype. In vivo experiments in immunodeficient athymic female Balb/c nu/nu mice confirmed the results obtained in vitro: the NOTCH1 inhibition decreased the growth rates of the subcutaneous xenografts formed by A549 and HCT116 tumor cells. Therefore, downregulation of the gene encoding the Notch1 receptor potentially reduces malignant characteristics of human lung and colorectal carcinoma cells.


[Developments in the last 10 years in diagnostic imaging discovery of renal carcinoma].
We have reviewed the files of 69 patients who had presented with cancer of the renal parenchyma between 1985 and 1994. In 20% of cases in 1985-1989 and in 40% of cases in 1990-1994 these tumours were discovered incidentally, in example before the occurrence of any suggestive symptoms. In 20% (1985-1989) of cases and 40% (1990-1994) of cases, the credit for this early detection was due to ultrasound study prescribed by the attending physician waiting a general health assessment or the follow-up of some other disease. The early diagnosis treating cancers at less advanced staged, which will probably improve the prognosis.


Conformational changes upon calcium binding and phosphorylation in a synthetic fragment of calmodulin.
We have recently investigated by far-UV circular dichroism (CD) the effects of Ca(2+) binding and the phosphorylation of Ser 81 for the synthetic peptide CaM [54-106] encompassing the Ca(2+)-binding loops II and III and the central alpha helix of calmodulin (CaM) (Arrigoni et al., Biochemistry 2004, 43, 12788-12798). Using computational methods, we studied the changes in the secondary structure implied by these spectra with the aim to investigate the effect of Ca(2+) binding and the functional role of the phosphorylation of Ser 81 in the action of the full-length CaM. Ca(2+) binding induces the nucleation of helical structure by inducing side chain stacking of hydrophobic residues. We further investigated the effect of Ca(2+) binding by using near-UV CD spectroscopy. Molecular dynamics simulations of different fragments containing the central alpha-helix of CaM using various experimentally determined structures of CaM with bound Ca(2+) disclose the structural effects provided by the phosphorylation of Ser 81. This post-translational modification is predicted to alter the secondary structure in its surrounding and also to hinder the physiological bending of the central helix of CaM through an alteration of the hydrogen bond network established by the side chain of residue 81. Using quantum mechanical methods to predict the CD spectra for the frames obtained during the MD simulations, we are able to reproduce the relative experimental intensities in the far-UV CD spectra for our peptides. Similar conformational changes that take place in CaM [54-106] upon Ca(2+) binding and phosphorylation may occur in the full-length CaM.


Neutrophils are major contributors to intraparenchymal lung IL-1 beta expression after hemorrhage and endotoxemia.
Acute lung injury and the acute respiratory distress syndrome (ARDS) are significant causes of morbidity and mortality following sepsis and hemorrhage. Increased IL-1beta production in the lung is important in the development of acute inflammatory lung injury. Although neutrophils are an important component of the inflammatory response that characterizes acute lung injury, there is little information to suggest that they are capable of initiating cytokine-mediated immune responses in the lung. To explore the role of neutrophils in the early stages of acute lung injury, we examined IL-1beta production by mouse lung neutrophils after hemorrhage and endotoxemia. There was a significant increase in IL-1beta expression among intraparenchymal pulmonary neutrophil/mononuclear cells (IPNMC) 1 h after hemorrhage or endotoxemia. IL-1beta was detected only in a neutrophil-rich fraction of the IPNMC, but not in T and B lymphocytes positively selected from the IPNMC. Cyclophosphamide (CTX)-treated neutropenic mice expressed significantly less IL-1beta in IPNMC after hemorrhage or endotoxemia compared with CTX-untreated controls. Immunohistochemical analysis of lung sections from mice after hemorrhage or endotoxemia revealed IL-1beta expression in infiltrating neutrophils. These data indicate that IL-1beta-producing neutrophils traffic to the lungs rapidly in response to hemorrhage or endotoxemia and support the concept that proinflammatory cytokine production by lung neutrophils may contribute to the development of lung injury after blood loss and sepsis.


Hemorrhagic colitis and pseudomelanosis coli in ipecac ingestion by proxy.
This report describes a toddler with chronic diarrhea, vomiting, and hypotonia due to surreptitious administration of syrup of ipecac by his mother (Munchausen's syndrome by proxy). Several features of this case distinguish it from previous reports of chronic ipecac ingestion in childhood: the development of grossly bloody stools; radiologic, endoscopic, and biopsy evidence of a chronic moderate colitis resembling ulcerative colitis; and the histologic finding of pseudomelanosis coli, providing an important clue to toxic ingestion. The significance and possible mechanism for genesis of pseudomelanosis coli is discussed. This case emphasizes the variability in presentation and difficulty in diagnosing long-term ipecac ingestion by proxy. Ipecac toxicity should be considered in children with unexplained colitis and vomiting.


[Quality assessment on the case reports in Chinese Acupuncture and Moxibustion based on the guideline for the case report of TCM in China].
To carry on the quality assessment of the case reports published in Chinese Acupuncture and Moxibustion. The case reports were retrieved electronically published in Chinese Acupuncture and Moxibustion from 2006 to 2016. The Writing guideline for case report of traditional Chinese medicine was adopted to assess the quality of case report, in which, 15 items were included. The percentage of each item was calculated as the quality score. Totally, 288 case reports were included. The reports on the title, patient's information, clinical manifestations and treatment measures were quite complete (accounting to over 90%). But the report was limited on the key words, abstract, background and the informed consent. The overall quality score was low (accounting to 88.19%). Of 288 case reports, only 34 case reports (accounting to 11.81%) were of the high quality. The overall quality score of the inclusive literatures was in the range from 29 to 31 points. It is necessary to improve the quality of case report on acupuncture and moxibustion. It is anticipated to develop the writing guideline for the case report on acupuncture and moxibustion for the contribution to the development of acupuncture and moxibustion.


Enantioselectivity in random deposition processes on template surfaces.
A molecular model is proposed to study the enantioselective adsorption of chiral species on metallic surfaces modified through the preadsorption of another chiral species, known as template surfaces. It is found that anisotropic and exclusive interactions among adsorbed species are essential factors in the enantioselective process. It is shown how the formation of compact structures explains the fact that an enantiomer of species B having the same symmetry as the template species A can be preferentially adsorbed with respect to the other enantiomer of species B, thus producing enantioselectivity. The model predicts enantioselectivity peaks on a limited range of the template coverage, as typically observed experimentally in some systems.


Endovascular Treatment of Vascular Injuries in the Craniocervical Region With a Graft Stent: A Single-Center Experience.
We aimed to evaluate the efficacy and safety of graft stent implantation in the endovascular treatment of vascular injuries in the craniocervical area. This study was carried out through the retrospective screening of eight (two females and six males) patients' records. Patients who used graft stents as an endovascular method were included in the study. The mean age of the patients was 43.6 years (with a range of 15-69 years). Due to different mechanisms, the patients had vascular injuries in the craniocervical region, and graft stent implantation was performed between 2010 and 2022. We evaluated patient demographics, admission symptoms, trauma mechanisms, angiographic findings, treatment modalities and materials, patient outcomes, and follow-up periods. Due to iatrogenesis for four patients, penetrating trauma for three patients, and blunt trauma for one patient, injuries were present in the right internal carotid artery {ICA} (n=1), left ICA (n=1), left common carotid artery {CCA} (n=3), right CCA (n=1), right vertebral artery (n=1), and left vertebral artery (n=1). Angiographically, pseudoaneurysm was detected in seven patients, and vascular rupture was detected in one patient using contrast agent extravasation. All patients who underwent the endovascular method had technical success. Since bleeding from the external carotid artery branches was seen in two patients, these branches were embolized with coils. No radiologically or neurologically pathological findings were recorded during the follow-up period (with a range of one week to 12 years). Graft stent use in the endovascular treatment of craniocervical vascular injuries is an operable, safe, and promising option, especially in patients with pseudoaneurysms and active bleeding.


Topical application of zinc-solutions: a new treatment for herpes simplex infections of the skin?
Eighteen patients experiencing 22 episodes of recurrent herpes simplex skin infections were treated with topical applications of a solution containing 4% zinc sulphate in water. In all patients, pain, tingling and burning stopped completely within the first 24 hours of zinc therapy. Crusting occurred within 1-3 days and no adverse effects were observed.


mcLARO: Multi-contrast learned acquisition and reconstruction optimization for simultaneous quantitative multi-parametric mapping.
To develop a method for rapid sub-millimeter T1 , T2 , T 2 * $$ {\mathrm{T}}_2^{\ast } $$ , and QSM mapping in a single scan using multi-contrast learned acquisition and reconstruction optimization (mcLARO). A pulse sequence was developed by interleaving inversion recovery and T2 magnetization preparations and single-echo and multi-echo gradient echo acquisitions, which sensitized k-space data to T1 , T2 , T 2 * $$ {\mathrm{T}}_2^{\ast } $$ , and magnetic susceptibility. The proposed mcLARO optimized both the multi-contrast k-space under-sampling pattern and image reconstruction based on image feature fusion using a deep learning framework. The proposed mcLARO method with R = 8 $$ R=8 $$ under-sampling was validated in a retrospective ablation study and compared with other deep learning reconstruction methods, including MoDL and Wave-MoDL, using fully sampled data as reference. Various under-sampling ratios in mcLARO were investigated. mcLARO was also evaluated in a prospective study using separately acquired conventionally sampled quantitative maps as reference standard. The retrospective ablation study showed improved image sharpness of mcLARO compared to the baseline network without the multi-contrast sampling pattern optimization or image feature fusion module. The under-sampling ratio experiment showed that higher under-sampling ratios resulted in blurrier images and lower precision of quantitative values. The prospective study showed that small or negligible bias and narrow 95% limits of agreement on regional T1 , T2 , T 2 * $$ {\mathrm{T}}_2^{\ast } $$ , and QSM values by mcLARO (5:39 mins) compared to reference scans (40:03 mins in total). mcLARO outperformed MoDL and Wave-MoDL in terms of image sharpness, noise suppression, and artifact removal. mcLARO enabled fast sub-millimeter T1 , T2 , T 2 * $$ {\mathrm{T}}_2^{\ast } $$ , and QSM mapping in a single scan.


Intestinal sclerosis with pseudo-obstruction in three dogs.
Intestinal sclerosis causing chronic intestinal pseudo-obstruction was diagnosed in 3 dogs. The pseudo-obstruction was characterized by vomiting and weight loss of 2 weeks' to 3 months' duration. A patent intestinal lumen was determined by contrast radiography and verified at surgery. Intestinal biopsy revealed diffuse atrophy, fibrosis, and mononuclear cell infiltration of the tunica muscularis. Each dog was euthanatized because of a progressive, deteriorating clinical course.


Validation of ESR analyzer using Westergren ESR method.
Erythrocyte sedimentation rate (ESR) is one of the most frequently ordered laboratory test. ESR analyzers were developed to provide a quick and efficient measure of ESR. We compared the results of ESR obtained by an ESR analyzer with those by the Westergren method in a group of 75 patients Linear regression analysis showed a good correlation between the two results (r = 0.818, p < 0.01). The intra class correlation was 0.82. The analyzer method had the advantages of safety, decreased technician time and improved patient care by providing quick results.


Three-Stream, Bicarbonate-Based Hemodialysis Solution Delivery System Revisited: With an Emphasis on Some Aspects of Acid-Base Principles.
Hemodialysis patients can acquire buffer base (i.e., bicarbonate and buffer base equivalents of certain organic anions) from the acid and base concentrates of a three-stream, dual-concentrate, bicarbonate-based, dialysis solution delivery machine. The differences between dialysis fluid concentrate systems containing acetic acid versus sodium diacetate in the amount of potential buffering power were reviewed. Any organic anion such as acetate, citrate, or lactate (unless when combined with hydrogen) delivered to the body has the potential of being converted to bicarbonate. The prescribing physician aware of the role that organic anions in the concentrates can play in providing buffering power to the final dialysis fluid, will have a better knowledge of the amount of bicarbonate and bicarbonate precursors delivered to the patient.


The Rcs phosphorelay system is specific to enteric pathogens/commensals and activates ydeI, a gene important for persistent Salmonella infection of mice.
Bacteria utilize phosphorelay systems to respond to environmental or intracellular stimuli. Salmonella enterica encodes a four-step phosphorelay system that involves two sensor kinase proteins, RcsC and RcsD, and a response regulator, RcsB. The physiological stimulus for Rcs phosphorelay activation is unknown; however, Rcs-regulated genes can be induced in vitro by osmotic shock, low temperature and antimicrobial peptide exposure. In this report we investigate the role of the Rcs pathway using phylogenetic analysis and experimental techniques. Phylogenetic analysis determined that full-length RcsC- and RcsD-like proteins are generally restricted to Enterobacteriaceae species that have an enteric pathogenic or commensal relationship with the host. Experimental data show that RcsD and RcsB, in addition to RcsC, are important for systemic infection in mice and polymyxin B resistance in vitro. To identify Rcs-regulated genes that confer these phenotypes, we took advantage of our observation that RcsA, a transcription factor and binding partner of RcsB, is not required for polymyxin B resistance or survival in mice. S. enterica serovar Typhimurium oligonucleotide microarrays were used to identify 18 loci that are activated by RcsC, RcsD and RcsB but not RcsA. Five of the 18 loci encode genes that contribute to polymyxin B resistance. One of these genes, ydeI, was shown by quantitative real-time PCR to be regulated by the Rcs pathway independently of RcsA. Additionally, the stationary-phase sigma factor, RpoS (sigmaS), regulates ydeI transcription. In vivo infections show that ydeI mutants are out-competed by wild type 10- to 100-fold after oral inoculation, but are only modestly attenuated after intraperitoneal inoculation. These data indicate that ydeI is an Rcs-activated gene that plays an important role in persistent infection of mice, possibly by increasing bacterial resistance to antimicrobial peptides.


Identification of Mycobacterium avium and Mycobacterium intracellulare isolated in Puerto Rico from clinical samples by the use of a non-radioactive DNA probe.
The Mycobacterium avium complex (MAC), especially M. avium, is an important opportunistic pathogen of AIDS patients in the United States. In Puerto Rico, the incidence of infections caused by MAC has not been determined. This is due, in part, to the difficulties associated to the microbiological identification of the microorganisms. In this work, a commercially available kit (AccuProbe, Gen-Probe, Inc., San Diego, CA) utilizing a DNA probe complementary to rRNA of M. avium and M. intracellulare was used to identify seventeen MAC strains and one unknown atypical mycobacterium recovered in culture in Puerto Rico from clinical samples. The results obtained revealed that M. avium was the predominant species recovered (83% of isolates tested). Only two cultures were identified as M. intracellulare. The unknown culture, which did not react with either probe, turned out to be M. gordonae. The probe tests not only are simple to perform, but provide cultural identification results in as little as two hours. This study, the first one of its kind in Puerto Rico, demonstrates that the nucleic acid probes for the cultural identification of M. avium and M. intracellulare offer the potential of providing a prompt diagnosis and much needed data on the epidemiology of MAC infections in Puerto Rico.


Microfluidic-aided fabrication of nanoparticles blend based on chitosan for a transdermal multidrug delivery application.
The aim of this work was to provide a microfluidic-aided fabrication of nanoparticles based on chitosan/poly(N-isopropylacrylamide-co-acrylic acid)/cellulose laurate [CS/P(NIPAAm-co-AAc/CL] blend for transdermal multidrug delivery applications. The scanning electron microscopy (SEM) and dynamic light scattering (DLS) results showed that the diameter sizes of samples were in the range from 200 to 300nm along with a narrow size distribution. Also, the CS-based nanoparticles containing tretinoin and clindamycin phosphate prepared using microfluidic technique exhibited a sustained control release of the drugs as well as minimum inhibitory and bactericidal concentrations compared to the samples fabricated via bulk mixing method. The thermal stability of the drugs loaded nanoparticles revealed a reduction in degradation for those fabricated by using microfluidic technique at 45°C for one month. Afterward, the in vivo assessments confirmed that by applying the microfluidically generated nanoparticles containing two drugs, a declined superficial reddening (erythema) and suitable transdermal permeation as well as residency were happened with respect to the those samples prepared via bulk mixing method and also the drugs solution alone. Finally, these CS-based nanoparticles showed sufficient potential used for transdermal multidrug delivery applications.


[Criteria for histopathologic diagnosis of thyroid cancer in a quick test of accuracy].
A quick test of accuracy of histopathological diagnosis of thyroid carcinoma was performed in May 2000 during the meeting of Polish thyroid cancer group (Committee for Epidemiology, Diagnosis and Treatment of Thyroid Carcinoma). 29 pathologists participated in the test and evaluated 8 cases of thyroid carcinoma and 14 benign thyroid lesions. All cases were chosen from the current material sent for pathologic evaluation to the Institute of Oncology in Gliwice due to diagnostic difficulties. In total, 591 diagnoses were made and were the subject of the presented analysis. They were compared with reference diagnosis in two aspects. First, the accuracy of the distinction between malignant and benign lesions was evaluated. 72.5% of diagnoses were concordant with the reference. The false diagnosis of cancer in a benign lesion was observed 133 times (22.5% of all diagnoses). A reverse error--a false exclusion of cancer--was seen in 29 diagnoses (4.9%). Chi 2 test revealed a statistically significant difference between the participants' diagnoses and reference ones (p < 0.0001). Overdiagnosis of cancer was the most frequent at the diagnosis of follicular or oxyphilic cancer. With reference to the diagnosis of cancer histotype, concordant diagnoses were seen in 40-47% of cases with the lowest accuracy of the diagnosis of oxyphilic (40% of correct diagnoses) and follicular (50%) cancer. The causes of false diagnoses may be divided in two groups: sample-related causes (sampling of surgical specimens, lack of standard description, insufficient number of samples, poor quality of staining) and diagnostic errors: non-compliance with diagnostic criteria and inappropriate setting of diagnoses, which require immunohistochemical confirmation.


Determination of haloperidol in biological samples with the aid of ultrasound-assisted emulsification microextraction followed by HPLC-DAD.
A rapid and simple quantitative method for preconcentration and determination of haloperidol in biological samples was developed using ultrasound-assisted emulsification microextraction, based on the solidification of floating organic droplet combined with HPLC-DAD. The effects of several factors were investigated. A total of 30 μL of 1-undecanol as an extraction solvent was injected slowly into a glass-centrifuge tube containing 4 mL alkaline sample solution that was located inside the ultrasonic water bath. The formed emulsion was centrifuged and the fine droplets of solvent were floated at the top of the test tube, then it was cooled in an ice bath and the solidified solvent was transferred into a conical vial, after melt, the analysis of the extract was carried out by HPLC. Under the optimal conditions, the extraction efficiencies were more than 90% and the preconcentration factors were obtained between 119-122. The LOQs were obtained between 4-8 μg/L and the calibration curves were linear within the range of 4-1000 μg/L. Finally this method was applied to the determination of haloperidol in plasma and urine samples in the range of μg/L and satisfactory results were achieved (RSDs <7%).


Characterization of molecular interactions between eosinophil cationic protein and heparin.
Eosinophil cationic protein (ECP) is currently used as a biomarker for airway inflammation. It is a heparin-binding ribonuclease released by activated eosinophils. Its cytotoxicity toward cancer cell lines is blocked by heparin. The objective of this study was to locate the heparin binding site of ECP by site-directed mutagenesis and construction of a synthetic peptide derived from this region. Synthetic heparin with > or =5 monosaccharide units showed strong inhibition of ECP binding to the cell surface. Analysis of ECP mt1 (R34A/W35A/R36A/K38A) showed that these charged and aromatic residues were involved in ECP binding to heparin and the cell surface. A potential binding motif is located in the loop L3 region between helix alpha2 and strand beta1, outside the RNA binding domain. The synthetic peptide derived from the loop L3 region displayed strong pentasaccharide binding affinity and blocked ECP binding to cells. In addition, ECP mt1 showed reduced cytotoxicity. Thus, the tight interaction between ECP and heparin acts as the primary step for ECP endocytosis. These results provide new insights into the structure and function of ECP for anti-asthma therapy.