Two Rationally Identified Novel Glitazones Reversed the Behavioral Dysfunctions and Exhibited Neuroprotection Through Ameliorating Brain Cytokines and Oxy-Radicals in ICV-LPS Neuroinflammatory Rat Model.
The present study has planned to evaluate the neuroprotective activity of two novel glitazones in a neuroinflammatory rat model. Two novel glitazones were selected from an in-house virtual library of glitazones based on their docking scores against peroxisome proliferator-activated receptor-gamma (PPAR-γ) protein and other parameters studied in in silico computational studies. Initially, an acute oral toxicity study was carried out for glitazones in rats to assess the toxicity profile and to determine the therapeutic range for neuroprotective evaluation. Prior to induction of neuroinflammation, the treatments with glitazones (G1 and G2) and standard pioglitazone were made for four consecutive days to respective groups. On the fifth day, the neuroinflammation was induced by intracerebroventricular (ICV) administration of lipopolysaccharides (LPS) (2 μg/μl) using stereotaxic apparatus. After 7 days, the rats were subjected to behavioral assessment followed by neurobiochemical evaluation and histopathological studies. The pre-treatment with glitazones at two dose levels (15 and 30 mg/kg) has significantly reversed behavioral dysfunctions. Glitazones have shown significant reduction in the levels of LPO, NO, TNF-α, and IL-1β and also increased the levels of antioxidant enzymes such as SOD, CAT, and GSH in the brain of LPS-administered rats. The neuroprotection exhibited by two novel glitazones is comparable with standard pioglitazone. The PPAR-γ-dependent amelioration of cytokines and oxy-radicals released by novel glitazones during neuroinflammatory conditions may be attributed to the reversal of behavioral dysfunctions through preventing the degeneration of neurons in major regions of the brain.


The characteristics of early diagnostic hypotheses generated by physicians (experts) and students (novices) at one medical school.
How hypotheses generated at the outset of a physician-patient encounter influence the physician's diagnostic reasoning has received relatively little attention in the literature. Yet, this activity modulates the efficiency and accuracy of the diagnostic process. The authors proposed the theory that physicians (experts) would generate less specific initial diagnostic hypotheses than would students (novices). In 1988 and 1989, the hypotheses generated by 32 practicing physicians and 39 third-year medical students at one medical school were analyzed for number, specificity, and breadth (i.e., range) of diagnoses, and for differences between those generated by the physicians and by the students. The hypotheses were formulated on the basis of the initially available data--chief complaint and its duration, and basic demographic descriptions--from patients in three clinical scenarios. Compared with the physicians, the students generated significantly more hypotheses and significantly more specific hypotheses. There was no significant difference between the groups in the breadths of the hypotheses they selected, that is, the numbers of broad categories of diagnosis covered by individuals' hypotheses.


Flexible fibre-optic bronchoscopy in the management of lung complications in cystic fibrosis.
Flexible fibre-optic bronchoscopy was performed under sedation in 24 children with cystic fibrosis. In eight cases bronchoscopy was carried out as a therapeutic procedure. Most children were subjectively improved, but objective evidence of change was minimal. Useful information was obtained in 9/16 children who underwent the procedure for diagnostic purposes. Information included sensitive identification of organisms responsible for lower respiratory symptoms in non-expectorating cases and identification of unsuspected gastro-oesophageal reflux.


Impact of exercise on continence in prostate cancer patients post robotic assisted radical prostatectomy: a systematic review.
Urinary incontinence is one of the most common long term side effects after robotic prostatectomy (RALP), and significantly impacts patient quality of life. Pelvic floor muscle training (PFMT) has been a standard part of the urologist's armamentarium for maximizing continence outcomes post-op. Recently, aerobic and resistance exercises have been described as improving functional outcomes post RALP. We performed a systematic review to determine the influence of exercise, in the form of PFMT, aerobic exercise, and resistance training, on incontinence post-RALP. This systematic review was performed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, with database searches performed on January 14, 2022 and again on August 10, 2022 to account for any new publications. The search identified 1675 papers. Of the 1675 papers, 1007 were found to be duplicates, leaving 668 total studies for screening. Of the 668 papers, nine met all inclusion criteria. Of the nine, four studies presented data from patients who had undergone RALP and were included in the final descriptive systematic review. Sayilan et al. and Milios et al. showed postoperative PFMT and physical activity resulted in significantly improved continence outcomes at 1 and 6 months and 2, 6, and 12 weeks postoperatively, respectively. Heydenreich et al. combined PFMT with an oscillating rod therapy, which was found to significantly improve both postoperative urinary continence and health related quality of life compared to PFMT and relaxation techniques alone. On the contrary, Goode et al. examined delivery of exercise information and demonstrated no difference in continence outcomes between focused telehealth PFMT program and generic prostate cancer education. Pelvic floor muscle training, with or without adjunct therapies, results in improved continence outcomes post RALP. Supervised training programs may or may not accelerate this finding. There is no recent literature to support or refute the benefit of aerobic exercise or resistance training on reducing post-prostatectomy incontinence after RALP.


Latissimus dorsi musculocutaneous flap: correction of donor-site defect with reverse latissimus flap.
A simple one-stage method for repair of the larger donor defect of the latissimus dorsi musculocutaneous flap is documented. This technique preserves a more natural appearance than could otherwise be obtained from a skin graft.


A model for sustainable laser tattoo removal services for adult probationers.
The purpose of this paper is to describe a sustainable free laser tattoo removal clinic for economically disadvantaged adult probationers. This paper describes the partnerships, methods and challenges/lessons learned from the implementation of a free monthly laser tattoo removal program for adult probationers within a medical school setting in California. Possible patients are identified via a collaboration with the county's Probation Department. Founded in 2016, this monthly program has provided tattoo removal services to >37 adult patient probationers, many of whom receive follow-up treatments. Clients seek to remove about four blue/black ink tattoos. Since its inception, 23 dermatology residents have volunteered in the program. Challenges to patients' ongoing participation primarily pertain to scheduling issues; strategies for overcoming barriers to participation are provided. No safety concerns have emerged. Programs such as this public-private partnership may benefit probationers by eliminating financial barriers associated with tattoo removal. This model supports the training of cohorts of dermatologists seeking community service opportunities related to laser medicine. Others seeking to implement a similar program may also consider expanding treatment days/times to facilitate access for working probationers, providing enrollment options for other health and social services (e.g. public insurance, food stamp programs) and hosting a mobile onsite clinic to address clients' physical and mental health needs. This paper describes a unique collaboration between law enforcement and a medical school and it may assist other jurisdictions in establishing free tattoo removal programs for the benefit of probationers. The methods described overcome challenges regarding the implementation of this specialized clinical service.


[Control of the postoperative pain].
The pain is a frequent symptom during the postoperative period and results in suffering and unnecessary risks for the patient. Studies show the inadequate pain relief after surgery and the relationship with erroneous assessment and non-acquaintance about analgesics methods. The article discuss the postoperative pain management which includes the use of nonsteroidal antiinflammatory drugs, opioids, cognitive-behavior interventions and high-tech like epidural catheter and patient-controlled analgesia systems. Besides the adequate pain control includes the discussion about ethical and economic aspects.


PERFORMANCE OF TWO DIFFERENT CLINICAL SCORING SYSTEMS IN DIAGNOSING DISTAL SENSORY POLYNEUROPATHY IN PATIENTS WITH TYPE-2 DIABETES.
Early diagnosis of distal peripheral neuropathy (DSPN) the commonest diabetes complications, helps prevent significant morbidity. Clinical parameters are useful for detection, but subjectivity and lack of operator proficiency often results in inaccuracies. Comparative diagnostic accuracy of Diabetic Neuropathy Symptom (DNS) score and Diabetic Neuropathy Examination (DNE) score in detecting DSPN confirmed by nerve conduction studies (NCS) has not been evaluated. This study compares the performance of these scores in predicting the presence of electro physiologically proven DSPN. The objective of this, study was to compare the diagnostic accuracy of DNS and DNE scores in detecting NCS proven DSPN in type-2 diabetics, and to determine the frequency of sub-clinical DSPN among type-2 diabetics. In this cross-sectional study the DNS score and DNE score were determined in 110 diagnosed type-2 diabetic patients. NCS were carried out and amplitudes, velocities and latencies of sensory and motor nerves in lower limb were recorded. Comparison between the two clinical diagnostic modalities and NCS using Pearson's chi square test showed a significant association between NCS and DNE scores (p-value =.003, specificity 93%). The DNS score performed poorly in comparison (p-value = .068, specificity 77%). When the two scores were taken in combination the specificity in diagnosing DSPN was greater (p-value = .018, specificity 96%) than either alone. 33% of patients had subclinical neuropathy. DNE score alone and in combination with DNS score is reliable in predicting DSPN and is more specific than DNS score in evaluating DSPN. Both tests lack sensitivity. Patients without any evidence of clinical neuropathy manifest abnormalities on NCS.


Normal ageing, impaired cognitive functioning and senile dementia--a mixture distribution analysis.
Dementia scores in the population of very old subjects (70 to > 95) do not demonstrate an obviously bimodal distribution. Heterogeneity analysis shows that the assumption of two distributions explains the data significantly better than a one-distribution model. The first distribution component can be regarded as representing the normal range of scores and the second the pathological range. An additional finding shows the normal range distribution shifting to the pathological range with increasing age.


SACM/CT Study of the dissociation/recombination dynamics of hydrogen peroxide on an ab initio potential energy surface. Part II. Specific rate constants k(E,J), thermal rate constants k infinity(T), and lifetime distributions.
Statistical adiabatic channel model/classical trajectory (SACM/CT) calculations of the dissociation/recombination dynamics of hydrogen peroxide, H(2)O(2) <--> 2HO, have been performed on an ab initio potential energy surface by Kuhn, Rizzo, Luckhaus, Quack, and Suhm (J. Chem. Phys. 1999, 111, 2565). Specific rate constants k(E,J), thermal rate constants k(infinity)(T), and lifetime distributions are determined. After averaging over J, the derived k(E,J) are in quantitative agreement with non-exponential time-profiles of HO formation recorded after overtone excitation of H(2)O(2) near the dissociation threshold by Scherer and Zewail (J. Chem. Phys. 1987, 87, 97). The thermal high pressure rate constants for HO recombination agree with experimental data as well and can be represented by k(rec,infinity)/10(-10) cm(3) molecule(-1) s(-1) approximately [0.376 (298 K/T)(0.47) + 0.013 (T/298 K)(0.74)] over the range 60-1500 K. Non-statistical lifetime distributions are suggested not to have been of major relevance for the available experiment.


Molecular cloning and sequencing of the murine gastrin gene.
Gastrin is a peptide hormone important in acid regulation, growth of enterochromaffin cells of the oxyntic mucosa, and smooth muscle contractility. We isolated a genomic clone of gastrin from a SV-129 murine genomic library. The murine gastrin gene contains an open reading frame of 101 amino acids. The deduced amino acid sequence has 91.1% homology with the rat and 67.3% homology with the human analogue. Southern blot analysis of the murine gastrin clone gave the same restriction pattern as that seen from mouse kidney genomic DNA, consistent with this being a single copy of the gastrin gene in the mouse genome. Transfection studies demonstrated that the murine gastrin gene expression is stimulated by epidermal growth factor to the same extent as the human gastrin gene.


[Activity of plasma dopamine-beta-hydroxylase in newborn infants. Implication in prematurity, maternal pathology and growth].
The aim of the study was to determine plasma dopamine-beta-hydroxylase activity (DBH) in newborn infants and possible changes with maturation, mode of delivery and maternal disease: pregnancy-induced hypertension and gestational diabetes. DBH activity was determined by high performance liquid chromatography from 82 neonates divided in 2 groups: group I: 27 neonates (age: 1 to 8 days) including 6 preterm and 21 full-term neonates; group II: 55 full-term neonates divided in 5 classes: A: vaginal delivery; B: forceps; C: elective caesarean section; D: vaginal delivery and maternal hypertension; E: vaginal delivery and gestational diabetes. The plasma DBH activity was low in neonates and not influenced by prematurity. Significantly lower DBH activity was found after caesarean section. Hypertension and gestational diabetes did not affect umbilical cord plasma DBH activity.


Predictions of angle dependent tortuosity and elasticity effects on sound propagation in cancellous bone.
The anisotropic pore structure and elasticity of cancellous bone cause wave speeds and attenuation in cancellous bone to vary with angle. Previously published predictions of the variation in wave speed with angle are reviewed. Predictions that allow tortuosity to be angle dependent but assume isotropic elasticity compare well with available data on wave speeds at large angles but less well for small angles near the normal to the trabeculae. Claims for predictions that only include angle-dependence in elasticity are found to be misleading. Audio-frequency data obtained at audio-frequencies in air-filled bone replicas are used to derive an empirical expression for the angle-and porosity-dependence of tortuosity. Predictions that allow for either angle dependent tortuosity or angle dependent elasticity or both are compared with existing data for all angles and porosities.


Fisher, Neyman, and Bayes at FDA.
The wise use of statistical ideas in practice essentially requires some Bayesian thinking, in contrast to the classical rigid frequentist dogma. This dogma too often has seemed to influence the applications of statistics, even at agencies like the FDA. Greg Campbell was one of the most important advocates there for more nuanced modes of thought, especially Bayesian statistics. Because two brilliant statisticians, Ronald Fisher and Jerzy Neyman, are often credited with instilling the traditional frequentist approach in current practice, I argue that both men were actually seeking very Bayesian answers, and neither would have endorsed the rigid application of their ideas.


Statistical mechanics and dynamics of a three-dimensional glass-forming system.
In the context of a classical example of glass formation in three dimensions, we exemplify how to construct a statistical-mechanical theory of the glass transition. At the heart of the approach is a simple criterion for verifying a proper choice of upscaled quasispecies that allow the construction of a theory with a finite number of "states." Once constructed, the theory identifies a typical scale xi that increases rapidly with lowering the temperature and which determines the alpha-relaxation time tau(alpha) as tau(alpha) approximately exp(muxi/T), with mu a typical chemical potential. The theory can predict relaxation times at temperatures that are inaccessible to numerical simulations.


Relation of polyamine biosynthesis to the initiation of sprouting in potato tubers.
The polyamines putrescine, spermidine, and spermine and their biosynthetic enzymes arginine decarboxylase, ornithine decarboxylase and S-adenosyl-l-methionine decarboxylase are present in all parts of dormant potato (Solanum tuberosum L.) tubers. They are equally distributed among the buds of apical and lateral regions and in nonbud tissues. However, the breaking of dormancy and initiation of sprouting in the apical bud region are accompanied by a rapid increase in ornithine decarboxylase and S-adenosyl-l-methionine decarboxylase activities, as well as by higher levels of putrescine, spermidine, and spermine in the apical buds. In contrast, the polyamine biosynthetic enzyme activities and titer remain practically unchanged in the dormant lateral buds and in the nonbud tissues. The rapid rise in ornithine decarboxylase, but not arginine decarboxylase activity, with initiation of sprouting suggests that ornithine decarboxylase is the rate-limiting enzyme in polyamine biosynthesis. The low level of polyamine synthesis during dormancy and its dramatic increase in buds in the apical region at break of dormancy suggest that polyamine synthesis is linked to sprouting, perhaps causally.


Clinical malaria and sickle cell disease among multiple family members in Chicago, Illinois.
Malaria is a disease of global importance and accounts for up to 500 million cases per year. Nearly all malaria cases in the United States occur among persons who have traveled to areas with ongoing malaria transmission. Among the cases of malaria reported in the United States in 2000-2005, 695 were in US residents under the age of 18 years. The association of malaria with the sickle cell hemoglobin is well described in Africa but is a rare occurrence in the United States. Here we report 5 cases of Plasmodium falciparum malaria in siblings of a family who had traveled to Africa without taking chemoprophylaxis. Two of the children had sickle cell anemia, and 1 of them developed severe life-threatening malaria and hemolysis. The 3 other siblings had sickle cell trait, 2 of whom had complicated malaria. Patients who have sickle cell disease and are infected with malaria are prone to hyperhemolytic crisis; therefore, this complication should be anticipated. The patients we describe emphasize the significance of prompt recognition of malaria and comorbidities and institution of appropriate treatment. The importance of antimalarial prophylaxis should be communicated to parents of children who are traveling to endemic areas as part of routine child care.


Rapid Fluorescence Sensor Guided Detection of Urinary Tract Bacterial Infections.
Urinary tract infections (UTI) are one of the most serious human bacterial infections affecting millions of people every year. Therefore, simple and reliable identification of the urinary tract pathogenic bacteria within a few minutes would be of great significance for diagnosis and treatment of clinical patients with UTIs. In this study, the fluorescence sensor was reported to guide the detection of urinary tract bacterial infections rapidly. The Ami-AuNPs-DNAs sensor was fabricated by the amino-modified Au nanoparticles (Ami-AuNPs) and six DNAs signal molecules, which bound to the urinary tract pathogenic bacteria and generated corresponding response signals. Further, based on the collected response signals, identification was performed by principal component analysis (PCA) and linear discriminant analysis (LDA). The Ami-AuNPs and Ami-AuNPs-DNAs were characterized by transmission electron microscopy, UV-vis absorption spectrum, Fourier transform infrared spectrum, dynamic light scattering and zeta potentials. Thereafter, the Ami-AuNPs-DNAs sensor was used to discriminate and identify five kinds of urinary tract pathogenic bacteria. Moreover, the quantitative analysis performance towards individual bacteria at different concentrations were also evaluated. The Ami-AuNPs-DNAs sensor were synthesized successfully in terms of spherical, well-dispersed and uniform in size, which could well discriminate five main urinary tract pathogenic bacteria with unique fingerprint-like patterns and was sufficiently sensitive to determine individual bacteria with a detection limit to 1×107 cfu/mL. Furthermore, the sensor had also been successfully applied to identify bacteria in urine samples collected from clinical UTIs. The developed fluorescence sensor could be applied to rapid and accurate discrimination of urinary tract pathogenic bacteria and holds great promise for the diagnosis of the disease caused by bacterial infection.


Roto-translational Raman spectra of pairs of hydrogen molecules from first principles.
We calculate the collision-induced, roto-translational, polarized, and depolarized Raman spectra of pairs of H(2) molecules. The Schrodinger equation of H(2)-H(2) scattering in the presence of a weak radiation field is integrated in the close-coupled scheme. This permits the accounting for the anisotropy of the intermolecular potential energy surface and thereby it includes mixing of polarizability components. The static polarizability invariants, trace and anisotropy, of two interacting H(2) molecules were obtained elsewhere [Li et al., J. Chem. Phys. 126, 214302 (2007)] from first principles. Here we report the associated spherical tensor components which, along with the potential surface, are input in the calculation of the supramolecular Raman spectra. Special attention is paid to the interferences in the wings of the rotational S(0)(0) and S(0)(1) lines of the H(2) molecule. The calculated Raman pair spectra show reasonable consistency with existing measurements of the polarized and depolarized Raman spectra of pairs of H(2) molecules.


Patterns of Medical Cannabis Use among Patients Diagnosed with Multiple Sclerosis.
To survey the pattern and benefits of medical cannabis use (MCU) in a cross section of persons with multiple sclerosis (PWMS). One hundred and fifteen subjects completed a 36-question survey online or on paper which queried aspects of their use of cannabis, including frequency of use, effect on symptoms, and changes in their use of prescription medications, as well asa number of key demographic variables such as age, gender, disease duration and clinical course, etc. All subjects were treated at a multiple sclerosis (MS) clinic in Connecticut and enrolled in the Connecticut Medical Marijuana Program (CTMMP). Self-reported benefit from cannabis use for two or more symptoms of MS was associated with relapsing remitting MS (RRMS) vs progressive (PMS) (OR 3.043, 95% CI 1.026-9.028, p=0.038) and less benefit for two or more symptoms for those who required a wheelchair vs. those who ambulated without assistance (OR .246, 95% CI .195-.797, p=0.016). General benefit from cannabis use was reported for mood disorders (p<0.001), insomnia (p<0.001), sensory symptoms, including pain (p<0.001), and muscle cramps and spasms (p<0.001). Furthermore, benefit was also significantly associated with symptom severity in the case of insomnia (OR 9.735, 95% CI 2.751-34.445, p<0.001), and cramps and spasms (OR 5.234, 95% CI 1.261-21.729, p=0.014). A significant proportion of respondents had stopped or reduced prescription medications (86% vs. 55%, p<0.001) as a function of finding cannabis more effective than prescription medications. These included opioids, benzodiazepines, muscle relaxers and other pain medications. MCU among PWMS can lead to the reduction or discontinuation of several categories of prescription medications for symptoms of MS. Persons reporting the most benefit from MCU tended to have a milder form of MS with less disability, in contrast to previous studies. This study confirms the benefit of cannabis in several common MS symptoms, extending these findings to show that benefit can be related to baseline severity of some symptoms.


Prospective evaluation of visual acuity assessment: a comparison of snellen versus ETDRS charts in clinical practice (An AOS Thesis).
first, to prospectively compare visual acuity (VA) scores obtained with Snellen charts versus Early Treatment Diabetic Retinopathy Study (ETDRS) charts in a "real world" retinal practice, and second, to see if there was a difference in visual acuity measurements obtained with ETDRS charts starting at 4 or 2 meters. Prospective, consecutive evaluation of patients who underwent best-corrected visual acuity testing of their right eye performed at a single seating by the same experienced, certified vision examiner in the same room with standardized low light conditions using a projected Snellen chart at 20 feet, and two different back-illuminated ETDRS charts placed 4 and 2 meters from the patient. One hundred sixty-three eyes were included in the study. The mean Snellen VA was 0.67 logMAR (20/94), ETDRS VA at 4 meters was 0.54 logMAR (~20/69), and ETDRS VA at 2 meters was 0.51 logMAR (~20/65). The mean difference was 6.5 letters better on the ETDRS chart (P=.000000001). As the VA worsened, there was increased variability between the charts and the mean discrepancy between charts also increased. Subgroup analysis revealed the greatest difference between charts was in the poor vision subgroup (<20/200) with a difference of 0.2 logMAR (10 letters; P=.0000002). Patients with exudative age-related macular degeneration (AMD) had the greatest disparity on vision testing, but patients with dry AMD and diabetic retinopathy also exhibited significant differences. Visual acuity scores were significantly better on ETDRS charts compared to Snellen charts. The difference was greatest with poor visual acuity (<20/200) and in patients with exudative AMD. Thus, caution should be exercised when comparing data using the different charts.


Assessment of cross-resistance potential to neonicotinoid insecticides in Bemisia tabaci (Hemiptera: Aleyrodidae).
Laboratory bioassays were carried out with four neonicotinoid insecticides on multiple strains of Bemisia tabaci (Gennadius) to evaluate resistance and cross-resistance patterns. Three imidacloprid-resistant strains and field populations from three different locations in the southwestern USA were compared in systemic uptake bioassays with acetamiprid, dinotefuran, imidacloprid and thiamethoxam. An imidacloprid-resistant strain (IM-R) with 120-fold resistance originally collected from Imperial Valley, California, did not show cross-resistance to acetamiprid, dinotefuran or thiamethoxam. The Guatemala-resistant strain (GU-R) that was also highly resistant to imidacloprid (RR=109-fold) showed low levels of cross-resistance when bioassayed with acetamiprid and thiamethoxam. However, dinotefuran was more toxic than either imidacloprid or thiamethoxam to both IM-R and GU-R strains as indicated by low LC50s. By contrast, a Q-biotype Spanish-resistant strain (SQ-R) of B. tabaci highly resistant to imidacloprid demonstrated high cross-resistance to the two related neonicotinoids. Field populations from Imperial Valley (California), Maricopa and Yuma (Arizona), showed variable susceptibility to imidacloprid (LC50s ranging from 3.39 to 115 microg ml(-1)) but did not exhibit cross-resistance to the three neonicotinoids suggesting that all three compounds would be effective in managing whiteflies. Yuma populations were the most susceptible to imidacloprid. Dinotefuran was the most toxic of the four neonicotinoids against field populations. Although differences in binding at the target site and metabolic pathways may influence the variability in cross-resistance patterns among whitefly populations, comparison of whitefly responses from various geographic regions to the four neonicotinoids indicates the importance of ecological and operational factors on development of cross-resistance to the neonicotinoids.


Primary orbital melanoma associated with oculodermal melanocytosis.
A 29-year-old, otherwise healthy man presented with an approximately 5-months' history of left-sided exophthalmos. The patient had a bluish-black pigmentation on his left upper lid, and black pigmentation on the left conjunctiva and sclera, since birth. CT examination revealed a retrobulbar tumor in the left orbit, and the left medial rectus muscle was wider than the right one. The left orbital cavity and the superior orbital fissure were enlarged. All of the examinations were negative in respect of another primary tumor outside the orbit or of tumor dissemination. At surgery, a pigmented tumor was found and removed. The orbital tissues were darkly pigmented. Histological examination of the excised tumor showed it to be an encapsulated, circumscribed mass. The tumor was built up of fusiform and spindle-shaped cells containing black pigmentation, with very few mitoses and without necrosis. There has been no recurrence or metastasis in 3 years of follow-up. The consequences of the tumorous transformation of oculodermal melanocytosis as reflected in the published literature and the special clinical and histopathological characteristics of our case are discussed.


Coping with stress in the workplace: implications for new health professionals.
Because health care professionals must provide high-quality care while simultaneously adjusting to the new demands of a rapidly changing health care system, work stress and possibly even burnout are prevalent issues for both senior professionals and recent health science graduates upon entry into the workforce. This article examines the experience of stress and the importance of coping abilities, particularly focusing on students enrolled in health professional courses and those who have recently entered the workforce. It also presents research pertaining to whether newly graduated health professionals are coping effectively with the demands of work. Suggestions for improving stress-coping abilities are given.


An exploration of midwives' and obstetricians' knowledge of genetic screening in pregnancy and their perception of appropriate counselling.
to describe levels of knowledge relevant to genetic screening in a sample of midwives and obstetricians in the late 1990s, and to compare these with those found by Smith et al. in London and Wales, and reported in 1994; to describe health professionals' perceptions of an appropriate counselling process relating to genetic screening in comparison with recognised good practice; and to consider links between knowledge and perceptions of the counselling process. a questionnaire study, including responses to a counselling scenario. responses were obtained from 81 midwives and obstetricians from maternity services in the North West of England. knowledge about procedures was very good, but knowledge about the probability of genetic abnormality was relatively poor, and respondents overestimated the efficacy and usefulness of tests. These findings were similar to those of Smith et al. (1994), suggesting that they are a good reflection of the national picture. In terms of reported information-giving and counselling practice, there were some respondents who would not check the woman's understanding of her baby's risk of a genetic abnormality, or the risk of a false result. Some respondents would give information based on their own (necessarily limited) experience, rather than national statistics, and give advice based on the choices they themselves would make. These findings reflect earlier, basic research on people's understanding of probabilistic information. the findings of this study, together with those of earlier work cited, suggest a need for education and training which includes a specific focus on biases in understanding this type of probabilistic information. They also raise the question as to why tests which provide probabilistic data have been introduced without consideration of the known problems in understanding such information.


CLASSIFYING PROCESSES: AN ESSAY IN APPLIED ONTOLOGY.
We begin by describing recent developments in the burgeoning discipline of applied ontology, focusing especially on the ways ontologies are providing a means for the consistent representation of scientific data. We then introduce Basic Formal Ontology (BFO), a top-level ontology that is serving as domain-neutral framework for the development of lower level ontologies in many specialist disciplines, above all in biology and medicine. BFO is a bicategorial ontology, embracing both three-dimensionalist (continuant) and four-dimensionalist (occurrent) perspectives within a single framework. We examine how BFO-conformant domain ontologies can deal with the consistent representation of scientific data deriving from the measurement of processes of different types, and we outline on this basis the first steps of an approach to the classification of such processes within the BFO framework.1.


[Peroral duodeno-jejunal biopsy in children. Indications and personal cases].
In this study we report our experience with 50 intestinal biopsies carried out in 35 children in a 14 months period (October 1979-December 1980) and we also describe the technique we use. The biopsy has been performed by two operators using the Crosby capsule, placed at the duodenojejunal flexure under fluoroscopic screening. For sedation we used oral Promazine and viscous xylocaine and i.v. Metoclopramide and Diazepam; the sedation has been classified in 4 degrees and resulted very good in 40 cases, good in 8 cases and sufficient in 2. The biopsy specimens has been examined with dissecting and light microscope and demonstrated 14 sub-total villous atrophy, 2 severe partial villous atrophy, 5 partial villous atrophy and 29 normal villous morphology. By this technique we made a diagnosis of Coeliac disease in 8 cases, suspected Coeliac disease in 3 cases, Dermatitis Herpetiformis in 3 cases and cow's milk proteins intolerance and post-enteritis syndrome in 1 case. No complications occurred during or after intubation. The AA. confirm the diagnostic value of this investigation, its safety and its very high degree of sensitivity superior to any other test of intestinal absorption.


ARFI variance of acceleration (VoA) for noninvasive characterization of human carotid plaques in vivo.
Rather than degree of stenosis, assessing plaque structure and composition is relevant to discerning risk for plaque rupture with downstream ischemic event. The structure and composition of carotid plaque has been assessed noninvasively using Acoustic Radiation Force Impulse (ARFI) ultrasound imaging. In particular, ARFI-derived peak displacement (PD) estimations have been demonstrated for discriminating soft (lipid rich necrotic core (LRNC) or intraplaque hemorrhage (IPH)) from stiff (collagen (COL) or calcium (CAL)) plaque features; however, PD did not differentiate LRNC from IPH or COL from CAL. The purpose of this study is to evaluate a new ARFI-based measurement, the variance of acceleration (VoA), for differentiating among soft and stiff plaque components. Both PD and VoA results were obtained in vivo for a human carotid plaque acquired in a previous study and matched to a histological standard analyzed by a pathologist. With VoA, plaque feature contrast was increased by an average of 60% in comparison to PD.


Personality Traits, Dimensions, and Suicidal Behavior in Posttraumatic Stress Disorder: Results From a Cross-Sectional Study in a Mexican Hospital.
Introduction Posttraumatic stress disorder (PTSD) may develop after exposure to stressful or life-threatening events and is linked to suicidal behavior. Personality is hypothesized to be a mediator of this risk though assessing factors influencing such findings has been difficult due to the psychiatric comorbidities of the disorder. Objective The aim of the study was to examine the relationship between personality and suicidal behavior in people with PTSD. Method This was a cross-sectional study with 67 participants diagnosed with PTSD who completed a structured interview (SCID-II), and an inventory (NEO-FFI) to gather personality characteristics. Data were collected and analyzed through statistical software, and the investigation period ranged from August 2020 to July 2021. Results Extraversion was correlated with suicide attempts, borderline traits predicted the number of these, and a negative relationship was found between conscientiousness and the same variable. Schizotypal traits were also positively correlated to self-harm. Extraversion, schizoid, borderline, and obsessive-compulsive traits were more likely to be diagnosed with either depressive and/or anxious disorders. Extraversion's association with suicidal attempts is inconsistent with previous studies, although the correlation of borderline traits with the same variable complies with existing knowledge. Schizotypal traits and their link with self-harm may be a novelty for this line of research, although the connection between extraversion, schizoid, borderline, and obsessive-compulsive traits along with depressive and anxious disorders echoes current literature. Conclusion Certain characteristics of personality are related to suicidal behavior in individuals with PTSD.


Computing with DNA.
We consider molecular models for computing and derive a DNA-based mechanism for solving intractable problems through massive parallelism. In principle, such methods might reduce the effort needed to solve otherwise difficult tasks, such as factoring large numbers, a computationally intensive task whose intractability forms the basis for much of modern cryptography.


Purinergic signaling in inflammatory renal disease.
Extracellular purines have a role in renal physiology and adaption to inflammation. However, inflammatory renal disease may be mediated by extracellular purines, resulting in renal injury. The role of purinergic signaling is dependent on the concentrations of extracellular purines. Low basal levels of purines are important in normal homeostasis and growth. Concentrations of extracellular purines are significantly elevated during inflammation and mediate either an adaptive role or propagate local inflammation. Adenosine signaling mediates alterations in regional renal blood flow by regulation of the renal microcirculation, tubulo-glomerular feedback, and tubular transport of sodium and water. Increased extracellular ATP and renal P2 receptor-mediated inflammation are associated with various renal diseases, including hypertension, diabetic nephropathy, and glomerulonephritis. Experimental data suggests P2 receptor deficiency or receptor antagonism is associated with amelioration of antibody-mediated nephritis, suggesting a pathogenic (rather than adaptive) role of purinergic signaling. We discuss the role of extracellular nucleotides in adaptation to ischemic renal injury and in the pathogenesis of inflammatory renal disease.


Binding of sigma(A) and sigma(B) to core RNA polymerase after environmental stress in Bacillus subtilis.
In Bacillus subtilis, the alternative sigma factor sigma(B) is activated in response to environmental stress or energy depletion. The general stress regulon under the control of sigma(B) provides the cell with multiple stress resistance. Experiments were designed to determine how activated sigma(B) replaces sigma(A) as a constituent of the RNA polymerase holoenzyme. Studies of the transcription of the sigma(A)-dependent stress gene clpE under sigma(B)-inducing conditions showed that expression was higher in a sigB mutant background than in the wild type. The relative affinities of sigma(A) and sigma(B) for binding to the core RNA polymerase (E) were determined by means of indirect surface plasmon resonance. The results showed that the affinity of sigma(B) for E was 60-fold lower than that of sigma(A). Western blot analyses with antibodies against sigma(A), sigma(B), and E showed that, after exposure to ethanol stress, the concentration of sigma(B) was only twofold higher than those of sigma(A) and E. Thus, the concentration of sigma(B) after stress is not high enough to compensate for its relatively low affinity for E, and it seems that additional mechanisms must be invoked to account for the binding of sigma(B) to E after stress.


Multigene phylogeny of the Coronophorales: morphology and new species in the order.
The phylogenetic relationships within Coronophorales have been debated because of uncertainty over the taxonomic usefulness of characteristics such as quellkörper, number of ascospores per ascus, presence of ascospore appendages, presence of subiculum and ascomatal vestiture. The phylogenetic relationships are examined with DNA sequence data from three nuclear genes targeting 69 taxa and 130 new sequences representing collections from Africa and the Americas. Analyses recovered monophyletic Bertiaceae, Chaetosphaerellaceae and Scortechiniaceae and a paraphyletic Nitschkiaceae. A single collection of Coronophora gregaria is included and Coronophoraceae is accepted. Bertiaceae is expanded to include Gaillardiella, and Thaxteria is synonymized with Bertia with a new combination, B. didyma. Three new species of Bertia are described: B. ngongensis from Kenya, B. orbis from Kenya and Costa Rica and B. triseptata from Ecuador and Puerto Rico. Bertia gigantospora is transferred from Nitschkia. Scortechiniaceae is confirmed for the quellkörper-bearing taxa including monotypic Biciliospora, Coronophorella, Neofracchiaea, Scortechiniella and Scortechiniellopsis. Tympanopsis is reinstated for T. confertula and T. uniseriata, while Scortechinia is more narrowly circumscribed to include S. acanthostroma and the new species, S. diminuspora from Ecuador. Cryptosphaerella is accepted in Scortechiniaceae including six new species from Kenya and Costa Rica, C. celata, C. costaricensis, C. cylindriformis, C. elliptica, C. globosa and C. malindensis. Spinulosphaeria is accepted in Coronophorales with uncertain family placement. The number of ascospores in the ascus is not phylogenetically useful in distinguishing genera within the order. The quellkörper continues to be an important character in defining the Scortechiniaceae, while taxa within the group show a mixture of morphological characteristics of varying phylogenetic importance. The presence of smooth versus spinulose subiculum aids in separating Tympanopsis and Scortechinia, and erumpent ascomata distinguish Cryptosphaerella species. Taxa within the Bertiaceae vary along the lines of robust, tuberculate, collapsing ascomata and large, hyaline to pigmented, septate ascospores.


Carbon dioxide gas endoscopy of the deep gluteal space.
The treatment of hip and pelvic pain associated with abnormalities of the deep gluteal space has evolved and increasingly involves endoscopic techniques with a saline expansion medium. This investigation presents a surgical technique utilizing carbon dioxide as the insufflation medium for deep gluteal space endoscopy in 17 cadaveric hips. This technique was successful in 94% (16/17) of the hips, allowing for visualization of the sciatic nerve, posterior femoral cutaneous nerve, pudendal nerve, branch of the inferior gluteal artery crossing the sciatic nerve, piriformis muscle, hamstring tendon origin, and lesser trochanter. Our experience suggests that gas expansion presents several advantages over fluid expansion.


Clinical factors that predict successful posterior urethral anastomosis with a gracilis muscle flap.
We evaluated the preoperative clinical factors that affect the surgical outcome of posterior urethral anastomosis (PUA) with a gracilis muscle flap (GMF) to determine which factors predict benefit from the use of the GMF. This was a retrospective analysis of 49 patients who underwent a delayed PUA with a GMF. A successful clinical outcome was defined as achieving a peak urinary flow rate greater than 15 mL/s at 3 and 12 months postoperatively without evidence of stricture recurrence on a retrograde urethrogram or cystourethroscopy at 3 months postoperatively. Multiple clinical factors were evaluated by use of univariate and multivariate analyses. The outcome of 21 of 49 patients (42.9%) was deemed successful. The mean age of the 49 patients was 37.2±13.5 years and the mean follow-up duration was 43.4±28.0 months. The length of the urethral defect was significantly shorter in patients with a successful outcome than in patients with an unsuccessful outcome (p=0.010). The outcome differed significantly depending on whether the patients had a previously successful urethroplasty (p=0.036) or whether they had suffered a pelvic bone injury (p=0.012). Multivariate logistic regression analyses revealed that a previous urethroplasty was the only preoperative clinical factor that significantly affected the surgical outcome in PUA with a GMF (odds ratio, 0.218; 95% confidence interval, 0.050 to 0.947; p=0.042). A history of previous urethroplasty is a preoperative clinical factor that significantly affects the surgical outcome in PUA with a GMF; the procedure is more likely to be successful in patients who have not previously undergone urethroplasty.


Development of a novel small antibody that retains specificity for tumor targeting.
For the targeted therapy of solid tumor mediated by monoclonal antibody (mAb), there have different models of rebuilding small antibodies originated from native ones. Almost all natural antibody molecules have the similar structure and conformation, but those rebuilt small antibodies cannot completely keep the original traits of parental antibodies, especially the reduced specificity, which gravely influences the efficacy of small antibodies. In this study, authors developed a novel mimetic in the form of V(H)FR1(C-10-)V(H)CDR1-V(H)FR2-V(L)CDR3-V(L)FR4(N-10) for a parental mAb induced with human breast cancer, and the mimetic moiety was conjugated to the C-terminal of toxicin colicin Ia. The novel fusion peptide, named protomimecin (PMN), was administered to MCF-7 breast cancer cells to demonstrate its killing competency in vitro and in vivo. Compared with original antibody-colicin Ia (Fab-Ia) and single-chain antibody-colicin Ia (Sc-Ia) fusion proteins, PMN retained the targeting specificity of parental antibody and could specifically kill MCF-7 cells in vitro. By injecting intraperitoneally into BALB/c athymic mice bearing MCF-7 tumors, with reduced affinity, PMN significantly suppressed the growth of tumors compared with control mice treated by toxicin protein, Fab-Ia protein, Sc-Ia protein or by PBS (p < 0.05). This novel mimetic antibody retained original specificity of parental antibody, and could effectively guide killer moiety to suppress the growth of breast cancer by targeted cell death.


Increased Central Arterial Stiffness after Spinal Cord Injury: Contributing Factors, Implications, and Possible Interventions.
Individuals with spinal cord injury (SCI) experience life-threatening cardiovascular events and various autonomic consequences in addition to the well-appreciated motor and neurological impairments. As a result, cardiovascular disease is a major cause of death after SCI, corresponding to a two-to-fourfold increased risk of cardiovascular events. A combination of neuroanatomical changes, unstable blood pressure, and rapid deconditioning as a result of decreased physical activity likely contributes to accelerated cardiovascular disease progression after SCI. Aortic pulse wave velocity (aPWV) is considered the gold-standard technique for evaluating central arterial stiffness, which itself is a correlate for greater cardiovascular disease risk in healthy individuals and a plethora of clinical conditions. In this review, we discuss central arterial stiffness after SCI, and demonstrate that it is consistently elevated in this population 2-3 m/sec, which corresponds to a 30-45% increased risk of cardiovascular mortality and an approximate 40-year acceleration of age-related cardiovascular decline. The potential factors contributing to increased central arterial stiffness are also reviewed in light of the available literature, including autonomic disruptions, blood pressure instability, metabolic changes, and physical inactivity. Further, measurement techniques, risk factors, cardiac dysfunction, and differences in arterial stiffness from able-bodied populations are discussed. Finally, potential therapeutic interventions for preventing or improving central arterial stiffening are also explored, including dietary, physical activity, and pharmacological strategies.


Evaluation of the Roche antigen rapid test and a cell culture-based assay compared to rRT- PCR for the detection of SARS-CoV-2: A contribution to the discussion about SARS-CoV-2 diagnostic tests and contagiousness.
The most sensitive method to detect SARS-CoV-2 relies on rRT-PCR; however, viral RNA can be detected weeks/months after clinical resolution. Since rRT-PCR cannot discern between non- and infectious virus, it is unclear whether the presence of viral RNA after recovery reflects infectious SARS-CoV-2. However, recent studies suggest a positive correlation between antigen rapid tests (Ag-RDT) and virus isolation that is more suited to assess contagiousness. To assess the utility of SARS-CoV-2 diagnostic tests in different settings we evaluated the performance of Ag-RDT-based and a cell culture-based SARS-CoV-2 assay in comparison to rRT-PCR. A total of 61 Nasopharyngeal-Swabs tested positive by cobasⓇ SARS-CoV-2 rRT-PCR were in parallel evaluated with the Roche Ag-RDT and a cell culture-based assay to detect SARS-CoV-2. SARS-CoV-2 was successfully isolated in 51/61 samples corresponding to 83.6%, which was 97.3% or 96.2% when considering samples with E-gene Ct-value <25 and <28, respectively. In comparison, the Ag-RDT showed an overall sensitivity of 85.2%, that increased to 100% and 96.2% using an E-gene Ct-value cut-off of <25 and <28, respectively. There was an overall good agreement between the commercial Ag-RDT and our in-house cell culture-based SARS-CoV-2 detection assay. However, SARS-CoV-2 could be isolated from two samples that tested negative by Ag-RDT. Our results support the use of the Roche Ag-RDT to detect SARS-CoV-2 exposure in large scale populations. However, it is recommended to use rRT-PCR, potentially in conjunction with cell culture-based SARS-CoV-2 assay, to support clinicians in making decisions regarding fragile patient groups.


Modeling the behavior of tritiated water vapor in a research reactor containment building.
Mathematical models were developed to predict the changes in tritiated water (HTO) concentrations in water pools and of HTO vapor in the Kyoto University Reactor (KUR) containment building in which approximately 3.4 x 10(2) GBq of HTO vapor had leaked from a heavy water facility for more than 1 y. Models reveal that the mechanism of HTO vapor transfer between air and water is controlled by two key parameters: the kinetic constant for HTO exchange and the evaporation rate constant from water to air. A model was constructed based on laboratory experiments using small glass dishes containing various volumes of HTO and was validated by comparing estimates to actual measurements for HTO concentration in water pools of various depths in the containment building. After the leakage from the heavy water facility had been stopped, the decrease in HTO concentration in the sub-pool could be described by this model with a half-life of 15 wk. A mathematical model was also developed to estimate the average HTO vapor concentration in air, which is strongly dependent on the ventilation system's operation even after the removal of the HTO sources. This is due to the continued release of HTO from the concrete material and is analogous to the dynamics of radon emanation. The amount of HTO that has emerged from the concrete was estimated using a model developed for HTO concentration changes in the containment building air, based on long-term monitoring.


[Claim review in occupational disability insurance].
In a deregulated market characterised by increasing competitiveness and improved conditions, care in assessing proposals in additional disability benefits will take on an even more significant role. The assessment has to be based on overall analysis of the moral and objective risk. This entails risk assessment of financial, professional, economic and medical factors, and should also include experience gained from the specific area of benefits involved. In terms of getting closer to our clients, the possibilities of limiting risk should be offered to an increasing extent on an individual, transparent and differentiated basis. Despite every effort to exercise caution, the time factor, i.e. the speed required to issue policies, should not be forgotten.


The inflammatory function of human IgA.
The prevailing concept regarding the immunological function of immunoglobulin A (IgA) is that it binds to and neutralizes pathogens to prevent infection at mucosal sites of the body. However, recently, it has become clear that in humans IgA is also able to actively contribute to the initiation of inflammation, both at mucosal and non-mucosal sites. This additional function of IgA is initiated by the formation of immune complexes, which trigger Fc alpha Receptor I (FcαRI) to synergize with various other receptors to amplify inflammatory responses. Recent findings have demonstrated that co-stimulation of FcαRI strongly affects pro-inflammatory cytokine production by various myeloid cells, including different dendritic cell subsets, macrophages, monocytes, and Kupffer cells. FcαRI-induced inflammation plays a crucial role in orchestrating human host defense against pathogens, as well as the generation of tissue-specific immunity. In addition, FcαRI-induced inflammation is suggested to be involved in the pathogenesis of various chronic inflammatory disorders, including inflammatory bowel disease, celiac disease, and rheumatoid arthritis. Combined, IgA-induced inflammation may be used to either promote inflammatory responses, e.g. in the context of cancer therapy, but may also provide new therapeutic targets to counteract chronic inflammation in the context of various chronic inflammatory disorders.


Fetal crown-rump length: reevaluation of relation to menstrual age (5-18 weeks) with high-resolution real-time US.
Because of recent challenges in the literature regarding the validity of the older crown-rump length (CRL) data developed with conventional static-image ultrasound scanners, the authors evaluated the relationship between CRL and menstrual age of fetuses in a population of 416 patients with good menstrual dates. By using a variety of commercially available transabdominal and transvaginal real-time ultrasound probes, the authors demonstrated that measurements can be made successfully for CRLs varying in size from 2 mm to 12 cm. Regression analysis of the data resulted in development of a new table for predicting menstrual age of fetuses on the basis of CRL measurements obtained between 5 and 18 weeks gestation. Although the magnitude of the raw residuals increased over time, the variability in predicting menstrual age was demonstrated to be relatively constant at +/- 8% (2 standard deviations) when expressed as a percentage of the predicted value. The accuracy in predicting menstrual age from CRL after 14 weeks was equivalent to but not better than conventional measurements such as biparietal diameter and femur length.


Morphology of the human cervical vagus nerve: implications for vagus nerve stimulation treatment.
The vagus nerve has gained a role in the treatment of certain diseases by the use of vagus nerve stimulation (VNS). This study provides detailed morphological information regarding the human cervical vagus nerve at the level of electrode implant. Eleven pairs of cervical vagus nerves and four pairs of intracranial vagus nerves were analysed by the use of computer software. It was found that the right cervical vagus nerve has an 1.5 times larger effective surface area on average than the left nerve [1,089,492 ± 98,337 vs 753,915 ± 102,490 μm(2), respectively, (P < 0.05)] and that there is broad spreading within the individual nerves. At the right side, the mean effective surface area at the cervical level (1,089,492 ± 98,337 μm(2)) is larger than at the level inside the skull base (630,921 ± 105,422) (P < 0.05). This could imply that the vagus nerve receives anastomosing and 'hitchhiking' branches from areas other than the brainstem. Furthermore, abundant tyrosine hydroxylase (TH)- and dopamine ß-hydroxylase (DBH)-positive staining nerve fibres could be identified, indicating catecholaminergic neurotransmission. In two of the 22 cervical nerves, ganglion cells were found that also stained positive for TH and DBH. Stimulating the vagus nerve may therefore induce the release of dopamine and noradrenaline. A sympathetic activation could therefore be part of mechanism of action of VNS. Furthermore, it was shown that the right cervical vagus nerve contains on average two times more TH-positive nerve fibres than the left nerve (P < 0.05), a fact that could be of interest upon choosing stimulation side. We also suggest that the amount of epineurial tissue could be an important variable for determining individual effectiveness of VNS, because the absolute amount of epineurial tissue is widely spread between the individual nerves (ranging from 2,090,000 to 11,683,000 μm(2)). We conclude by stating that one has to look at the vagus nerve as a morphological entity of the peripheral autonomic nervous system, a composite of different fibres and (anastomosing and hitchhiking) branches of different origin with different neurotransmitters, which can act both parasympathetic and sympathetic. Electrically stimulating the vagus nerve therefore is not the same as elevating the 'physiological parasympathetic tone', but may also implement catecholaminergic (sympathetic) effects.


Assessing multimedia/multipathway exposures to inorganic arsenic at population and individual level using MERLIN-Expo.
In this study, we report on model simulations performed using the newly developed exposure tool, MERLIN-Expo, in order to assess inorganic arsenic (iAs) exposure to adults resulting from past emissions by non-ferrous smelters in Belgium (Northern Campine area). Exposure scenarios were constructed to estimate external iAs exposure as well as the toxicologically relevant As (tAs, i.e., iAs, MMA and DMA) body burden in adults living in the vicinity of the former industrial sites as compared to adults living in adjacent areas and a reference area. Two scenarios are discussed: a first scenario studying exposure to iAs at the aggregated population level and a second scenario studying exposure at the individual level for a random sub-sample of subjects in each of the three different study areas. These two scenarios only differ in the type of human related input data (i.e., time-activity data, ingestion rates and consumption patterns) that were used, namely averages (incl. probability density functions, PDFs) in the simulation at population level and subject-specific values in the simulation at individual level. The model predictions are shown to be lower than the corresponding biomonitoring data from the monitoring campaign. Urinary tAs levels in adults, irrespective of the area they lived in, were under-predicted by MERLIN-Expo by 40% on average. The model predictions for individual adults, by contrast, under-predict the biomonitoring data by 7% on average, but with more important under-predictions for subjects at the upper end of exposure. Still, average predicted urinary tAs levels from the simulations at population level and at individual level overlap, and, at least for the current case, lead to similar conclusions. These results constitute a first and partial verification of the model performance of MERLIN-Expo when dealing with iAs in a complex site-specific exposure scenario, and demonstrate the robustness of the modelling tool for these situations.


Informed patient consent for defaulter tracing: should we obtain it?
Active default tracing is an integral part of tuberculosis (TB) programmatic control. It can be differentiated into the tracing of defaulters (patients not seen at the clinic for > or =2 months) and 'late patients' (late for their scheduled appointments). Tracing is carried out to obtain reliable information about who has truly died, transferred out or stopped treatment, and, if possible, to persuade those who have stopped treatment to resume. This is important because, unlike routine care for non-communicable diseases, TB has the potential for transmission to other members of the community, and therefore presents the issue of the rights of the individual over the rights of the community. For this reason, default or 'late patient' tracing (defined together as default tracing in this article) has been incorporated into standard practice in most TB programmes and, in many industrialised countries, it is also a part of public health legislation. In resource-poor countries with limited access to phones or e-mails, default tracing involves active home visits. In this Unresolved Issues article, we discuss the need for patient consent within both the programmatic and the research context; we describe how this subject arose during operational research training at the Research Institute of Tuberculosis in Japan; we provide comments from individuals who are experienced and skilled at international and national TB control; and finally we offer some conclusions about the way forward. This is not an easy subject, and we welcome open debate on the issue.


The colonial microtexture of human mycobacterial strains isolated in Burma.
Sixteen strains of Mycobacterium tuberculosis isolated in Burma were investigated for microcolonial texture using the thin section technique developed at the WHO Collaborating Centre in Prague. The strains were grown in deep (Sula's liquid medium) and surface cultures (Loevenstein-Jensen medium). Their colonies killed by 10% formol were embedded in 2% agar and paraffin, cut by a Reichert microtome and stained by the Ziehl-Neelsen technique. According to the surface texture and deep growth pattern, the Burmese strains were divided in three different groups. The European type was characterized by a growth strictly confined to the surface of the Loevenstein-Jensen medium, the African type by combined surface and subsurface growth, and the Burmese type not seen in Europe and Africa by non acid-fast granular and acid-fast colonies with distinct formation of strongly acid-fast cords both in surface and subsurface growth.


Correlations between polymorphisms in genes coding elements of dopaminergic pathways and body mass index in overweight and obese women.
Dopamine is considered to be crucial for food craving and intake, drug abuse and electrical brain stimulation. Increased levels of dopamine occur after energy intake in the dorsal striatum. In the ventral tagmental area, dopamine is responsible for motivation. There is a natural synaptic dopamine level, and as a result its activity is controlled by density of receptors, amount of released neurotransmitter, and defectiveness of re-uptake by specific transporters. In our study, we wanted to investigate if there is a correlation between mean BMI values and VNTR polymorphisms in SLC6A3 (rs28363170) and DRD4 genes. Chosen gene fragments were amplified using polymerase chain reaction on the DNA template obtained from 506 women. The products of the reaction were electrophoresed and visualised in 3% agarose gel. The genotyping data was analysed with Kruskal-Wallis tests (p 〈 0.05). In the case of SLC6A3, statistically significant differences in mean BMI were found in the group of obese women (p 〈 0.05) but not for the whole population of women with normal weight or with overweight (p 〉 0.05). The mean BMI was higher for the SS genotype than for combined LL and LS genotypes. The difference in mean BMI values for variants of DRD4 was significant for the whole studied population and in the obese group (p 〉 0.05), and the higher value was correlated with the presence of a variant with seven or more repeats of 48 bp motif. When the two analysed polymorphisms were combined, the spread between the mean BMI values became greater than for single genes. This suggests that the effect on body mass of these two polymorphisms may combine and cause hypo-functionality of the dopaminergic reward system.


Fluticasone propionate induced alterations to lung function and the immunopathology of asthma over time.
Inhaled corticosteroids are the most widely used treatment for asthma, a disease characterised by both functional and immunopathological abnormalities. This study investigated the relative effects of inhaled corticosteroids on these two features of asthma over time. A randomised, double blind, placebo controlled, parallel group study with inhaled fluticasone propionate, (FP 2 mg daily) was conducted in 27 patients with asthma. Following baseline analysis, the study tested the effects of short term (two weeks) and longer term (eight weeks) treatment. At each time point (0, 2, and 8 weeks) lung function tests were performed and endobronchial biopsy specimens obtained to determine the distribution and number of lymphocyte, macrophage and eosinophil subsets using immunohistological analysis. Twenty three patients completed the study, 11 on FP and 12 placebo. FEV1, delta FEV1, FEF25-75, and FEV1/FVC all improved after two weeks of FP treatment. This improvement was maintained but not increased after eight weeks. PC20FEV1 showed a trend to increase but was not significantly improved at eight weeks. No significant changes were seen in the placebo group. The numbers of T cells, macrophages, and eosinophils in the bronchial wall were reduced by two weeks of treatment with FP but were unaltered by placebo. The improvement offered by FP continued over the eight week period. Reductions in CD4:CD8 ratio and numbers of activated (EG2+) eosinophils were only significant after eight weeks of treatment. These results reveal that FP influences both functional and immunopathological parameters of asthma. Temporal relationships suggest that these are parallel but not necessarily interrelated effects. While short term treatment is effective in "normalising" the functional abnormalities in asthma, the impact of FP on bronchial inflammation appears to be progressive, taking up to eight weeks and more.


Calcified amorphous tumor located on a severely calcified mitral annulus in a patient with normal renal function.
A calcified amorphous tumor (CAT) of the heart is a rare, nonneoplastic, intracavitary cardiac mass. Histological examination shows that it contains calcified and amorphous fibrous material with underlying chronic inflammation. Surgical excision is generally recommended to avoid future embolism. The risk of embolism has been reported to be especially high in mitral-annular-calcification-related CAT, which constitutes a subgroup of CAT that is often associated with end-stage renal disease. A case of a CAT attached to the anterior annulus of the mitral valve that was easily removed with a light touch of the forceps through aortotomy is reported.


[Role of imaging in the diagnostic and therapeutic algorithms of breast cancer].
Early diagnosis and prevention have the most significant effect on overall disease specific outcome; 90% of all breast cancer cases could be cured if diagnosed early and treated accurately. As for all diagnostic methods the most important requirement for diagnostic imaging is to detect breast cancer in its early stage, and to determine accurate tumor staging, in order to select the appropriate therapy. Its role is to monitor the effectiveness of therapy, to follow up patients reliably for early detection of recurrent disease. The spectrum of radiological imaging methods in breast cancer became broader in the past two decades; imaging that provides functional or metabolic data and whole body information such as CT, MRI and PET-CT are now available besides common X-ray and ultrasound mammography. The MRI is getting more and more important for the detection and characterization of breast cancer. Multimodal imaging techniques provide more accurate analysis, which is confirmed by increasing statistics authentically, but none of the imaging methods was specific enough to provide histological diagnosis. However, imaging-guided biopsies enable precise histological or cytological confirmation.


Enhancement of hepatitis B surface antigen production by adenosine 5'-monophosphate in culture of recombinant Chinese hamster ovary cells.
Adenosine 5'-monophosphate was found effective in enhancing hepatitis B surface antigen (HBsAg) production in the culture of recombinant Chinese hamster ovary (CHO) cells, but it markedly inhibited cell growth. A culture strategy with periodical medium changes was established to increase HBsAg production and avoid the AMP-induced inhibition of cell growth. The enhanced energy supply might be one of the reasons for the increase in HBsAg production in the presence of AMP.


Unstable resonators with distributed saturable gain and nonuniform reflectivity outcouplers in the geometrical optics limit.
An existing geometrical optics method for calculating the longitudinal and transverse dependence of the mode intensities in unstable resonators with sharp-edged feedbacks mirrors and distributed saturable gain is modified to include the nonuniform reflectivity of the outcoupling feedback mirror. Results show that the mode extends increasingly outward as the gain increases, so the size of a limiting aperture must be chosen with care to prevent unwanted diffraction. An attempt to prescribe an arbitrary spatially limited output function of a loaded cavity and to find the required mode and reflectivity profiles yields spatially unlimited functions.


Etiology of Inguinal Hernias: A Comprehensive Review.
The etiology of inguinal hernias remains uncertain even though the lifetime risk of developing an inguinal hernia is 27% for men and 3% for women. The aim was to summarize the evidence on hernia etiology, with focus on differences between lateral and medial hernias. Lateral and medial hernias seem to have common as well as different etiologies. A patent processus vaginalis and increased cumulative mechanical exposure are risk factors for lateral hernias. Patients with medial hernias seem to have a more profoundly altered connective tissue architecture and homeostasis compared with patients with lateral hernias. However, connective tissue alteration may play a role in development of both subtypes. Inguinal hernias have a hereditary component with a complex inheritance pattern, and inguinal hernia susceptible genes have been identified that also are involved in connective tissue homeostasis. The etiology of lateral and medial hernias are at least partly different, but the final explanations are still lacking on certain areas. Further investigations of inguinal hernia genes may explain the altered connective tissue observed in patients with inguinal hernias. The precise mechanisms why processus vaginalis fails to obliterate in certain patients should also be clarified. Not all patients with a patent processus vaginalis develop a lateral hernia, but increased intraabdominal pressure appears to be a contributing factor.


Tracking and evaluation of dendritic cell migration by cellular magnetic resonance imaging.
Cellular magnetic resonance imaging (MRI) is a means by which cells labeled ex vivo with a contrast agent can be detected and tracked over time in vivo. This technology provides a noninvasive method with which to assess cell-based therapies in vivo. Dendritic cell (DC)-based vaccines are a promising cancer immunotherapy, but its success is highly dependent on the injected DC migrating to a secondary lymphoid organ such as a nearby lymph node. There the DC can interact with T cells to elicit a tumor-specific immune response. It is important to verify DC migration in vivo using a noninvasive imaging modality, such as cellular MRI, so that important information regarding the anatomical location and persistence of the injected DC in a targeted lymph node can be provided. An understanding of DC biology is critical in ascertaining how to label DC with sufficient contrast agent to render them detectable by MRI. While iron oxide nanoparticles provide the best sensitivity for detection of DC in vivo, a clinical grade iron oxide agent is not currently available. A clinical grade (19) Fluorine-based perfluorcarbon nanoemulsion is available but is less sensitive, and its utility to detect DC migration in humans remains to be demonstrated using clinical scanners presently available. The ability to quantitatively track DC migration in vivo can provide important information as to whether different DC maturation and activation protocols result in improved DC migration efficiency which will determine the vaccine's immunogenicity and ultimately the tumor immunotherapy's outcome in humans.


Who should pay for intensive behavioural intervention in autism? A parent's view.
The evidence that early intensive behavioural intervention (IBI) is effective for young children with autism has persuaded parents worldwide to finance and advocate for IBI. Intensive behavioural intervention uses applied behavioural analysis to address the deficits of autism with an individualized and systematic approach. Communication, social, cognitive and adaptive gains are seen in the majority of children; a sizeable minority can catch up to near normal functioning, under ideal conditions. However there is not universal acceptance amongst professionals that IBI is the most proven intervention. What level of evidence is required for Australian states to provide adequate public funds for IBI?


Neovascularization of the disc in pars planitis.
Neovascularization of the disc (NVD) was present in 9 of 163 patients with pars planitis. In all cases, NVD was unilateral and observed in eyes with recent exacerbation of the inflammatory process. To reduce intraocular inflammation, all nine eyes were treated with varying combinations of topical, periocular, and systemic corticosteroids. In addition to corticosteroids, one eye received Argon laser photocoagulation, two eyes underwent peripheral cryotherapy, and one eye was treated with both Argon laser photocoagulation and peripheral cryotherapy. With decrease or disappearance of intraocular inflammation, NVD resolved in all cases without recurrence during follow-up study, which ranged from 6 to 189 (mean, 81) months. Rhegmatogenous retinal detachments developed in two eyes treated with peripheral cryotherapy. Both detachments were successfully repaired with surgery. Control of intraocular inflammation appears to be the key factor for regression of NVD in pars planitis. If NVD does not regress or vitreous hemorrhage occur, photocoagulation and peripheral cryotherapy may be beneficial.


Cytoplasmic retention and nuclear import of 5S ribosomal RNA containing RNPs.
Nuclear export of newly transcribed 5S ribosomal RNA in Xenopus oocytes occurs in the context of either a complex with the ribosomal protein L5 (5S RNP) or with the transcription factor IIIA (7S RNP). Here we examine nuclear import of 5S RNA, L5 and TFIIIA. The 5S RNP shuttles between nucleus and cytoplasm and only 5S RNA variants which can bind to L5 gain access to the nucleus. The 7S RNP is retained in the cytoplasm. Only TFIIIA which is not bound to 5S RNA is imported into the nucleus. As a novel mechanism for cytoplasmic retention, we propose that RNA binding masks a nuclear localization sequence in TFIIIA. In contrast to the nuclear import of L5, import of TFIIIA is sensitive towards the nuclear localization sequence (NLS) competitor p(lys)-BSA, suggesting that these two proteins make use of different import pathways.


Factor Structure and Internal Consistency on a Reduced Version of the Revised Test of Need for Cognitive Closure.
The need for cognitive closure is a construct postulated by Kruglanski that explains the motivational aspects which influence decision-making and its impact on the social environment. Initially, it was assessed through a unidimensional scale, later criticized for its poor satisfactory reliability and validity. Regarding these criticisms, Pierro and Kruglanski developed a new 14-item scale to measure two dimensions, which were not previously evaluated: urgency tendency and permanence tendency. Although the Revised Test of Need for Cognitive Closure is more economical in terms of assessment time, it would be optimal to develop a reduced test that can assess faster while maintaining validity and reliability. The present research aims to reduce the Revised Test of Need for Cognitive Closure scale to the Argentinian context. To this end, we worked on a non-experimental design, assessing this scale within a sample of 690 Argentinian university students (Women = 81.16%, Men = 18.84%), and proceeded to perform reliability, as well as confirmatory factor analysis, convergent validity, and factorial invariance analysis. The results indicate a bi-factorial structure of a Need for Cognitive Closure instrument with eight items and two dimensions: urgency tendency (α = 0.76) and permanence tendency (α = 0.64), suggesting good reliability in both of them. In addition, well convergent validity was checked with other validated instruments, and finally, the factor loadings were shown to be invariant. In conclusion, it was demonstrated the reliability and validity of reducing the Revised Test of Need for Cognitive Closure in our social environment.


Content and Quality of Information about Stroke in Wikipedia across Multiple Languages.
Given the high contribution of stroke to the global burden of disease, there is a need for good-quality information on Web platforms such as Wikipedia. This study aimed to describe the quality of the Wikipedia articles on stroke written in different languages. We studied the world's 30 most spoken languages. With the DISCERN score, we evaluated the quality of the information within the Wikipedia articles. Three investigators assessed each of the texts translated to English. We also registered the word count, the number of references, and if the text referred to the emergency status of stroke, cues to suspect a stroke, and allusions to endovascular treatment. There is a Wikipedia article for stroke in 23 out of the 30 languages. The mean DISCERN score was 35 29.9 ± 9.2. Overall quality ranged from 3/5 in 26.1% to 1/5 in 17.4%. Word count had a mean of 36 3,145.8 ± 3,048.9 words, and the texts included a mean of 43.1 ± 57.3 references; 69.6% of the articles referred to stroke as a medical emergency, 52.2% included awareness symptoms, and 34.8% included endovascular management among the stroke treatments. Three pages included steroids as part of the stroke treatment. The DISCERN score was not correlated with the number of speakers, but it was positively correlated with the number of references (r = 0.90, p < 0.001) and the number of words (r = 0.78, p < 0.001) in the articles. The analyzed Wikipedia articles do not contain relevant and up-to-date information to the general population. Further, the content varies widely across the different languages and is missing for some of them. The missing versions disproportionally affect millions of potential information seekers in undeveloped countries.


Spontaneous and Therapeutic-Induced Mechanisms of Functional Recovery After Stroke.
With increasing rates of survival throughout the past several years, stroke remains one of the leading causes of adult disability. Following the onset of stroke, spontaneous mechanisms of recovery at the cellular, molecular, and systems levels ensue. The degree of spontaneous recovery is generally incomplete and variable among individuals. Typically, the best recovery outcomes entail the restitution of function in injured but surviving neural matter. An assortment of restorative therapies exists or is under development with the goal of potentiating restitution of function in damaged areas or in nearby ipsilesional regions by fostering neuroplastic changes, which often rely on mechanisms similar to those observed during spontaneous recovery. Advancements in stroke rehabilitation depend on the elucidation of both spontaneous and therapeutic-driven mechanisms of recovery. Further, the implementation of neural biomarkers in research and clinical settings will enable a multimodal approach to probing brain state and predicting the extent of post-stroke functional recovery. This review will discuss spontaneous and therapeutic-induced mechanisms driving post-stroke functional recovery while underscoring several potential restorative therapies and biomarkers.


[Chest high-resolution CT features analysis in predicting the progression of asbestosis].
Objective: To analyze the radiological characteristics of chest high-resolution computed tomography (HRCT) of patients with asbestosis, and to investigate the signs of predicting the disease progression of asbestosis. Methods: A prospective method was used to enroll 68 patients with asbestosis who were regularly followed up from 2013 to 2016. The radiological characteristics of patients with asbestosis were described by the International Classification of HRCT for Occupational and Environmental Respiratory Diseases (ICOERD) , and the differences between patients with and without progression were compared during the observation period. The Cox proportional hazards regression model was used to analyze the chest HRCT radiological signs predicting the progression of asbestosis. Results: The study included 68 patients with asbestosis aged (65.5±7.8) years old, of which 64.7% (44/68) were female, 29.4% (20/68) had a history of smoking. There was no significant difference in age, sex, smoking and asbestos exposure between patients with progressive asbestosis (20.6%, 14/68) and patients without progressive asbestosis (79.4%, 54/68) (P>0.05) . Chest HRCT of patients with asbestosis showed irregular and/or linear opacities, of which 5.9% (4/68) were accompanied by honeycombing. Irregular and/or linear opacities were mainly lower lung preponderant, often accompanied with ground glass opacity and mosaic perfusion. 98.5% (67/68) had pleural abnormalities, of which 39.7% (27/68) had diffuse pleural thickening with parenchymal bands and/or rounded atelectasis. The analysis of multivariable Cox proportional hazard regression showed that the risk of the progression of asbestosis was increased with higher irregular and/or linears opacities cores (HR=1.184, 95%CI: 1.012-1.384, P=0.034) and the appearance of honeycombing (HR=6.488, 95%CI: 1.447-29.097, P=0.015) . Conclusion: The irregular and/or linear opacities scores and honeycombing on chest HRCT are independent influencing factors for predicting the disease progression of asbestosis.


Atezolizumab and nab-Paclitaxel in Advanced Triple-Negative Breast Cancer: Biomarker Evaluation of the IMpassion130 Study.
Understanding the impact of the tumor immune microenvironment and BRCA1/2-related DNA repair deficiencies on the clinical activity of immune checkpoint inhibitors may help optimize both patient and treatment selection in metastatic triple-negative breast cancer. In this substudy from the phase 3 IMpassion130 trial, immune biomarkers and BRCA1/2 alterations were evaluated for association with clinical benefit with atezolizumab and nab-paclitaxel (A+nP) vs placebo and nP in unresectable (P+nP) locally advanced or metastatic triple-negative breast cancer. Patients were randomly assigned 1:1 to nab-paclitaxel 100 mg/m2 (days 1, 8, and 15 of a 28-day cycle) and atezolizumab 840 mg every 2 weeks or placebo until progression or toxicity. Progression-free survival and overall survival were evaluated based on programmed death-ligand 1 (PD-L1) expression on immune cells (IC) and tumor cells, intratumoral CD8, stromal tumor-infiltrating lymphocytes, and BRCA1/2 mutations. PD-L1 IC+ in either primary or metastatic tumor tissue was linked to progression-free survival and overall survival benefit with A+nP. PD-L1 IC+ low (26.9%; 243 of 902 patients) and high (13.9%; 125 of 902 patients) populations had improved outcomes that were comparable. Intratumoral CD8 and stromal tumor-infiltrating lymphocytes positivity (sTIL+) were associated with PD-L1 IC+ status; improved outcomes were observed with A+nP vs P+nP only in CD8+ and sTIL+ patients who were also PD-L1 IC+. BRCA1/2 mutations (occurring in 14.5% [89 of 612 patients]) were not associated with PD-L1 IC status, and PD-L1 IC+ patients benefited from A+nP regardless of BRCA1/2 mutation status. Although A+nP was more efficacious in patients with richer tumor immune microenvironment, clinical benefit was only observed in patients whose tumors were PD-L1 IC+.


Circadian rhythm of atrioventricular conduction predicts long-term survival in patients with chronic atrial fibrillation.
The R-R interval of the electrocardiogram during atrial fibrillation (AF) appears absolutely irregular. However, the Poincaré plot of the R-R interval reveals a sector shape of distribution that is unique to AF. Furthermore, the height of lower envelope (LE1.0) of the distribution and the degree of scatter above the envelope (scattering index) may reflect the refractoriness and concealment of atrioventricular (AV) conduction, respectively. We previously observed that both the LE1.0 and scattering index show clear circadian rhythms in patients with chronic AF and that the rhythms are blunted in those with congestive heart failure and chronic AF. In the present study, we examined if the blunted circadian rhythm of the AV conduction has prognostic value in patients with chronic AF. We studied a retrospective cohort of 120 patients who underwent 24h Holter monitoring at baseline. During an observation period of 33 +/- 16 mon, there were 25 deaths (21%) including 13 cardiac and 8 stroke deaths. All patients showed significant circadian rhythms in both LE1.0 and scattering index with acrophases occurring at night; however, patients dying subsequently from cardiac causes, but not those from fatal stroke were blunted in the circadian rhythms (the amplitudes were < 55% of those in surviving patients). Furthermore, the reduced circadian amplitude of scattering index was an increased risk for cardiac death even after adjustment of coexisting cardiovascular risks [adjusted relative risk (95% confidence interval) per 1-SD decrement, 4.24 (1.54-11.6)]. When patients were divided by the circadian amplitude of the scattering index of 36.5 msec (mean minus 1-SD), the 5yr cardiac mortality below and above the cutoff was 57 and 6%, respectively (log-rank test, p < 0.001). We conclude that the blunted circadian rhythm of AV conduction is an independent risk for cardiac death in patients with chronic AF.


Cancer Stem Cell Subpopulations Are Present Within Metastatic Head and Neck Cutaneous Squamous Cell Carcinoma.
Cancer stem cells (CSCs) have been identified in many cancer types including primary head and neck cutaneous squamous cell carcinoma (HNcSCC). This study aimed to identify and characterize CSCs in metastatic HNcSCC (mHNcSCC). Immunohistochemical staining performed on mHNcSCC samples from 15 patients demonstrated expression of the induced pluripotent stem cell (iPSC) markers OCT4, SOX2, NANOG, KLF4, and c-MYC in all 15 samples. In situ hybridization and RT-qPCR performed on four of these mHNcSCC tissue samples confirmed transcript expression of all five iPSC markers. Immunofluorescence staining performed on three of these mHNcSCC samples demonstrated expression of c-MYC on cells within the tumor nests (TNs) and the peri-tumoral stroma (PTS) that also expressed KLF4. OCT4 was expressed on the SOX2+/NANOG+/KLF4+ cells within the TNs, and the SOX2+/NANOG+/KLF4+ cells within the PTS. RT-qPCR demonstrated transcript expression of all five iPSC markers in all three mHNcSCC-derived primary cell lines, except for SOX2 in one cell line. Western blotting showed the presence of SOX2, KLF4, and c-MYC but not OCT4 and NANOG in the three mHNcSCC-derived primary cell lines. All three cell lines formed tumorspheres, at the first passage. We demonstrated an OCT4+/NANOG+/SOX2+/KLF4+/c-MYC+ CSC subpopulation and an OCT4+/NANOG-/SOX2+/KLF4+/c-MYC+ subpopulation within the TNs, and an OCT4+/NANOG+/SOX2+/KLF4+/c-MYC+ subpopulation within the PTS of mHNcSCC.


Transition of adolescents with special health care needs: review and analysis of the literature.
A review and analysis of 43 transition studies published from 1982 through 2003 was conducted. The studies reviewed represent the diverse purposes of international researchers for examining transition issues and questions. Findings of this literature review indicate that transition research is in early stages of development. A number of limitations were associated with these studies, including the lack of theoretical frameworks, the use of valid and reliable instruments, and research designs lacking adequate controls. Future research studies are needed that overcome the design limitations of past investigations.


Risk factors for Plasmodium falciparum infection in the Kenyan Highlands: a cohort study.
Malaria transmission in African highland areas can be prone to epidemics, with minor fluctuations in temperature or altitude resulting in highly heterogeneous transmission. In the Kenyan Highlands, where malaria prevalence has been increasing, characterising malaria incidence and identifying risk factors for infection is complicated by asymptomatic infection. This all-age cohort study, one element of the Malaria Transmission Consortium, involved monthly follow-up of 3155 residents of the Kisii and Rachuonyo South districts during June 2009-June 2010. Participants were tested for malaria using rapid diagnostic testing at every visit, regardless of symptoms. The incidence of Plasmodium falciparum infection was 0.2 cases per person, although infections were clustered within individuals and over time, with the majority of infections detected in the last month of the cohort study. Overall, incidence was higher in the Rachuonyo district and infections were detected most frequently in 5-10-year-olds. The majority of infections were asymptomatic (58%). Travel away from the study area was a notable risk factor for infection. Identifying risk factors for malaria infection can help to guide targeting of interventions to populations most likely to be exposed to malaria.


Doped bottom-contact organic field-effect transistors.
The influence of doping on doped bottom-gate bottom-contact organic field-effect transistors (OFETs) is discussed. It is shown that the inclusion of a doped layer at the dielectric/organic semiconductor layer leads to a significant reduction in the contact resistances and a fine control of the threshold voltage. Through varying the thickness of the doped layer, a linear shift of threshold voltage V T from -3.1 to -0.22 V is observed for increasing thickness of doped layer. Meanwhile, the contact resistance at the source and drain electrode is reduced from 138.8 MΩ at V GS = -10 V for 3 nm to 0.3 MΩ for 7 nm thick doped layers. Furthermore, an increase of charge mobility is observed for increasing thickness of doped layer. Overall, it is shown that doping can minimize injection barriers in bottom-contact OFETs with channel lengths in the micro-meter regime, which has the potential to increase the performance of this technology further.


Diagnostic utility of CD205 in breast cancer: Simultaneous detection of myoepithelial cells and dendritic cells in breast tissue by CD205.
CD205 can be used to detect myoepithelial cells (MECs) and dendritic cells (DCs) in breast tissue. However, the usefulness of CD205 immunostaining in the pathological diagnosis of breast tumors is not fully understood. The objective of this study was to re-evaluate CD205 co-expression with other MEC markers, such as p63 and CD10, in nonneoplastic and neoplastic breast tissue and to evaluate its pathological diagnostic utility in these types of breast cancer. Nonneoplastic breast tissue samples with a terminal duct lobular unit and duct were obtained from fibroadenoma and mastopathy patients. Neoplastic breast tissue samples included ductal carcinoma in situ (DCIS) (n=43) and invasive ductal carcinoma (IDC) (n=60), including the tubule-forming type (n=20). These specimens were investigated by CD205, p63, and CD10 immunostaining. In addition to p63 and CD10, CD205 was expressed on MECs in nonneoplastic breast and DCIS tissue samples; CD205 was simultaneously detected on DCs that had infiltrated DCIS and IDC tumor nests. CD205 was expressed on cancer cells themselves in only 7.3% of the breast cancer samples. The number of intratumoral CD205⁺ DCs in tubular IDC was significantly higher than that in DCIS (P<0.01). Because CD205 was simultaneously detected on MECs and DCs in the same breast tissue sections, it may be useful for distinguishing tubular IDC from DCIS.


Colistin plasma concentrations are not associated with better clinical outcomes in patients with pneumonia caused by extremely drug-resistant Pseudomonas aeruginosa.
In some cases, colistin is the only treatment option for infections caused by the very drug-resistant Pseudomonas aeruginosa. However, in the past decade, there have been questions concerning its pharmacokinetics and concentration at the site of infection. In this scenario, its use in a difficult-to-treat infection like pneumonia is currently debatable. This is a clinical pharmacokinetic study of colistin in patients with multidrug-resistant P. aeruginosa pneumonia. Our findings demonstrate that colistin exposure is associated with worse clinical outcomes rather than better clinical outcomes, implying that other therapeutic options should be explored in this clinical setting.


A review of methods for storage of corneas for keratoplasty.
This article reviews the various methods used for the storage of the donor cornea for keratoplasty. The methods have been classified in terms of the duration of storage as (a) short-term (b) intermediate term (c) long-term and (d) very long-term. The practical importance of the moist-chamber method of short-term storage has been discussed. A short report on a new intermediate-term corneal storage medium using steroid as a lysosome membrane stabilizer has also been included. Organ culture of corneas for long-term storage is not popular in the developing countries due to lack of appropriate storage facilities. Cryopreservation as a long-term storage technique still attracts researchers' attention.


Dynamic correlation between pressure-induced protein structural transition and water penetration.
Water penetration into the hydrophobic interior of proteins has been postulated to be a primary force driving pressure-induced denaturation of proteins. The water penetration model is supported by several theoretical and simulation studies, although its direct evidence is lacking. In this study, 1 micros all-atom molecular dynamics simulations of ubiquitin in explicit water at high and low pressures are performed to examine the water penetration model. The high-pressure simulation starts from a crystal structure at atmospheric pressure and successfully reproduces the main characteristics of a high-pressure structure obtained by NMR. Water penetrates into a specific hydrophobic core of the protein and is ejected from the interior several times. The structural transition results from the relative stabilization of a preexisting metastable structure by applying pressure. A time correlation analysis demonstrates that the transition is accompanied by the penetration of water within a time scale comparable to the relaxation time of water itself. Simultaneous water penetration only occurs above a certain high pressure.


Age-mediated transcriptomic changes in adult mouse substantia nigra.
Substantia nigra pars compacta (SNpc) is highly sensitive to normal aging and selectively degenerates in Parkinson's disease (PD). Until now, molecular mechanisms behind SNpc aging have not been fully investigated using high throughput techniques. Here, we show early signs of aging in SNpc, which are more evident than in ventral tegmental area (VTA), a region adjacent to SNpc but less affected in PD. Aging-associated early changes in transcriptome were investigated comparing late middle-aged (18 months old) to young (2 months old) mice in both SNpc and VTA. A meta-analysis of published microarray studies allowed us to generate a common "transcriptional signature" of the aged (≥ 24 months old) mouse brain. SNpc of late-middle aged mice shared characteristics with the transcriptional signature, suggesting an accelerated aging in SNpc. Age-dependent changes in gene expression specific to SNpc were also observed, which were related to neuronal functions and inflammation. Future studies could greatly help determine the contribution of these changes to SNpc aging. These data help understand the processes underlying SNpc aging and their potential contribution to age-related disorders like PD.


Plain and ion-pair thin-layer chromatography of synthetic dyes on an admixture of silica gel G and barium sulfate in an aqueous ethanol system.
An easy, inexpensive, and accurate method for the analysis of synthetic dyes by means of ion-pair thin-layer chromatography (IPTLC) on mixed sorbent phases containing silica gel G and barium sulfate in an aqueous ethanol system is studied. The effect of the composition of the sorbent phases has a major effect on the hundred-fold relative migration rate, as also does the effect of the ion-pairing reagent as the impregnant. Compact and sharp spot application yields very good binary and ternary separations and enables their clear identification. IPTLC has better separations on mixed sorbent phases, which are not possible on plain mixed phases in thin-layer chromatography. The method can be applied for the trace analysis of synthetic dyes in various natural and synthetic samples.