Radiologically isolated syndrome: An update on a rare entity.
Our understanding of radiologically isolated syndrome (RIS) is evolving, as new data emerge on the clinical characterization and the pathophysiological nature of this rare entity. This topical review aims to (1) outline state-of-the-art clinical and magnetic resonance imaging findings of RIS research; (2) raise the main obstacles to RIS research; (3) discuss the most controversial issues of current RIS findings; and (4) highlight potential strategies for upcoming research studies.


Assigning categorical information to Japanese medical terms using MeSH and MEDLINE.
This paper reports on the assigning of MeSH (Medical Subject Headings) categories to Japanese terms in an English-Japanese dictionary using the titles and abstracts of articles indexed in MEDLINE. In a previous study, 30,000 of 80,000 terms in the dictionary were mapped to MeSH terms by normalized comparison. It was reasoned that if the remaining dictionary terms appeared in MEDLINE-indexed articles that are indexed using MeSH terms, then relevancies between the dictionary terms and MeSH terms could be calculated, and thus MeSH categories assigned. This study compares two approaches for calculating the weight matrix. One is the TF*IDF method and the other uses the inner product of two weight matrices. About 20,000 additional dictionary terms were identified in MEDLINE-indexed articles published between 2000 and 2004. The precision and recall of these algorithms were evaluated separately for MeSH terms and non-MeSH terms. Unfortunately, the precision and recall of the algorithms was not good, but this method will help with manual assignment of MeSH categories to dictionary terms.


[Histological studies on the roots of twelve species of Sect. Microdiscus and Sect. Adenophora of the genus Adenophora].
This paper reports the root structures of Adenophora lamarkii Fisch, A. hunanensis Nannf., A. hunanensis Nannf. subsp. huadungensis Hong, A. trachelioides Maxim., A. trachelioides Maxim. subsp. giangsuensis Hong, A. remotiflora (Sieb. et Zucc.) Miq. derived from Sect. Microdiscus of the Genus Adenophora, and A. stenanthina (Ledeb.) Kitagawa, A. stenanthina (Ledeb.) Kitagawa subsp. xifengensis P. F. Tu et Y. S. Zhou, A. liliifolioides Pax et Hoffm., A. capillaris Fisch., A. tetraphylla Fisch., A. triphylla (Thunb.) A. DC. derived from Sect. Adenophora of the Genus Adenophora. Based on the histological studies of 23 species, 5 subspecies and 2 varieties of the Genus Adenophora, a Key of histological characters is given.


Minor salivary gland tumours of upper aerodigestive tract: a clinicopathological study.
The aim of this retrospective study of 56 patients with minor salivary gland tumours (MSGTs) of the upper aerodigestive tract is to present demographic features, distribution of tumours as well as methods and results of treatment performed in our institution over a 10-year period. Of 221 patients with salivary gland tumours, 56 patients with MSGT were selected. There were 36 female and 20 male patients aged from 8 to 81 years. Male-to-female ratio was 1 : 2 in the group of benign MSGT and 1 : 1.7 in the group of malignant tumours. The palate was the most frequent site of MSGT (45.6%), followed by buccal mucosa (19.3%). Of all MSGTs 63.2% were malignant, and 36.8% were benign. Adenoid cystic carcinoma was the most common neoplasm (31.6%), followed by pleomorphic adenoma (29.8%). Surgery was the method of choice in the treatment of patients with MSGT. Postoperative defects were reconstructed by prosthetic obturators, local flaps, and free radial forearm flap. Relative survival for patients with malignant MSGT was 88% at three years and 71.5% at five years. MSGTs are more frequent in females and predominantly affect the palate. Malignant MSGTs are more common than benign.


Heterogeneity and the modelling of bacterial spore death: the case of continuously decreasing death rate.
Models for the inactivation of bacterial spores for the case of continuously decreasing death rate are reviewed and extended to show that it is not possible to distinguish between one particular model based upon the innate heterogeneity of the population and that based upon the acquisition of heat resistance during the heating process. Two innate heterogeneity models have been fitted to published data.


The ocular distribution of bunolol in the eyes of albino and pigmented rabbits.
The ocular administration of a 50 microL instillation of bunolol hydrochloride, a beta 1- and beta 2- adrenoceptor blocking agent, resulted in significantly higher drug levels in the choroid/retina, iris, and ciliary body of pigmented rabbits compared with albino rabbits following topical administration. The concentrations in these tissues also persisted longer in the pigmented rabbits' eyes. However, no statistically significant differences in tissue levels were observed in the cornea or conjunctiva. The results of this study support the previously reported finding with timolol which showed longer retention of the drug in the iris, ciliary, choroid, and retina of pigmented rabbits than albinos.


The activity of interneurons during locomotion in the in vitro necturus spinal cord.
1. Less than two segments of the cervical spinal cord of the mudpuppy (Necturus maculatus) is sufficient to generate a locomotor rhythm with application of N-methyl-D-aspartic acid (NMDA). We have recorded intracellularly from rhythmically active interneurons in these segments and classified them according to their phase of firing within the step cycle and their afferent input. 2. Four classes of interneurons were found: flexor, flexor-->extensor, extensor, and extensor-->flexor. Interneurons that burst during the transition from flexion to extension or vice versa are referred to as "transitional" interneurons and represent the majority (68%) of rhythmically active interneurons studied in the mudpuppy spinal cord. 3. All flexor interneurons received only inhibitory input from cutaneous and dorsal root afferents, whereas the flexor-->extensor interneurons that responded received only excitatory input from dorsal root and cutaneous afferents. All extensor interneurons and all but one extensor-->flexor interneuron received no afferent input from the cutaneous or dorsal root afferents we stimulated. 4. Other interneurons have been classified as "tonic" cells. They fire continuously when the mudpuppy is walking and are silent when the mudpuppy is not walking. These interneurons receive no afferent input from the sources tested and may be responsible for turning locomotion on and off. 5. In conclusion, the presence of many transitional interneurons with specific patterns of afferent input may be required for the phasing of legged locomotion. We believe the in vitro preparation of the mudpuppy spinal cord and forelimb is an excellent model for studying the firing properties of interneurons during legged locomotion.


The inhibitory effect of normal immunosuppressive protein on lymphocytes mediating natural killing activity.
Normal immunosuppressive protein (Nip) was found to have a marked in vitro inhibitory effect on lymphocytes mediating natural cytotoxic activity against the myeloid cell line K-562. The inhibitory activity of Nip was most marked when tested at an effector: target cell ratio of 10:1. When Nip was washed away, a significant recovery of the cytotoxic activity of the natural killer (NK) cells occurred. In control experiments in which human albumin was employed instead of Nip, no inhibitory activity was observed; on the contrary, a stimulatory effect of the NK activity was encountered. The present study shows that Nip suppresses the functions of NK cells just as it inhibits the function of other lymphocytes.


Cytoplasmic mRNA-protein complexes of chicken muscle cells and their role in protein synthesis.
Irradiation of chicken muscle cells with ultraviolet light (254 nm) to cross-link RNA and protein moieties was used to examine the polypeptide complements of cytoplasmic mRNA-protein complexes (mRNP). The polypeptides of translationally active mRNP complexes released from polysomes were compared to the repressed nonpolysomal cytoplasmic (free) mRNP complexes. In general, all of the polypeptides present in free mRNPs were also found in the polysomal mRNPs. In contrast to polysomal mRNPS, polypeptides of Mr 28 000, 32 000, 46 000, 65 000 and 150 000 were either absent or present in relatively smaller quantities in free mRNP complexes. On the other hand, the relative proportion of polypeptides of Mr 130 000 and 43 000 was higher in free mRNPs than in polysomal mRNP complexes. To examine the role of cytoplasmic mRNP complexes in protein synthesis or mRNA metabolism, the changes in these complexes were studied following (a) inhibition of mRNA synthesis and (b) heat-shock treatment to alter the pattern of protein synthesis. Actinomycin D was used to inhibit mRNA synthesis in chick myotubes. The possibility of newly synthesized polypeptides of cytoplasmic mRNP complexes being assembled into these complexes in the absence of mRNA synthesis was examined. These studies showed that the polypeptides of both free and polysomal mRNP complexes can bind to pre-existing mRNAs, therefore suggesting that polypeptides of mRNP complexes can be exchanged with a pool of RNA-binding proteins. In free mRNP complexes, this exchange of polypeptides is significantly slower than in the polysomal mRNP complexes. Heat-shock treatment of chicken myotubes induces the synthesis of three polypeptides of Mr = 81 000, 65 000 and 25 000 (heat-shock polypeptides). Whether this altered pattern of protein synthesis following heat-shock treatment could affect the polypeptide composition of translationally active polysomal mRNPs was examined. The results of these studies show that, compared to normal cells, more newly synthesized polypeptides were assembled into polysomal mRNPs following heat-shock treatment. A [35S]methionine-labeled polypeptide of Mr = 80 000 was detected in mRNPs of heat-shocked cells, but not of normal cells. This polypeptide was, however, detected by AgNO3 staining of the unlabeled polypeptide of mRNP complexes of normal cells. These results, therefore, suggest that the assembly of newly synthesized 80 000-Mr polypeptide to polysomal mRNPs was enhanced following induction of new heat-shock mRNAs. The results of these studies reported here have been discussed in relation to the concept that free mRNP complexes are inefficiently translated in vivo.(ABSTRACT TRUNCATED AT 400 WORDS)


A continuum theory and an experiment for the ion-induced swelling behavior of articular cartilage.
Swelling of normal bovine articular cartilage equilibrated in NaCl solutions was dimensionally measured in thin strips of tissue. The ion-induced strains show that free swelling of articular cartilage is anisotropic and inhomogeneous. For the molar concentrations used, contraction increased linearly with concentration, defining a "coefficient of chemical contraction" (alpha c). Isometrically constrained specimens registered a rise in tensile force followed by stress relaxation. An extension of the biphasic theory incorporating this ion-induced strain is proposed. This theory can describe the equilibrium anisotropic swelling behavior of cartilage and explain the transient force history observed in the isometric experiment.


A School-Based Multilevel Study of Adolescent Suicide Ideation in California High Schools.
To assess the between-school variation in suicide ideation and to estimate the contribution of school-level attributes, student-level characteristics, and 2 cross-level interactions (school by student) to student suicide ideation. A secondary analysis of the California Healthy Kids Survey in 2 large and representative samples of California high schools and students: 2009-2011 and 2011-2013. This is a population sample of all public high school students (grades 9 and 11) in California. Analyses were first conducted on surveys administered in the 2011-2013 academic years to 790 schools with 345 203 students and replicated on surveys administered in 2009-2011 to 860 schools with 406 313 students. School-level suicide ideation rates ranged between 4% and 67%, with a median of 19.3% and mean of 20.0% (SD, 5.7%). Student suicide ideation was explained by student-level characteristics (R2 = .20) and to a larger extent by school-level attributes (R2 = .55). Student-level characteristics predictive of suicide ideation included, sex, ethnic and racial affiliation, victimization, and perceptions of school climate. In both samples, school size and average level of academic achievement were not associated with rates of school suicide ideation. Schools with a larger number of girls and higher levels of victimization had higher rates of suicide ideation in both samples. The hypotheses regarding cross-level interactions were not confirmed. Differences among schools in student suicide ideation are meaningful. The findings suggest an emphasis on the role of schools in prevention programs, public health campaigns to reduce suicide, multilevel research, and theory development.


EPIDEMIOLOGY OF GASTROINTESTINAL NEUROENDOCRINE TUMORS IN A U.S. COMMERCIALLY INSURED POPULATION.
To estimate incidence and prevalence of gastrointestinal neuroendocrine tumors (GI NETs) in U.S. commercially insured patients. This was a retrospective, cross-sectional study using 2009 to 2014 data from MarketScan and PharMetrics commercial claims databases. Patients were 18 to 64 years old, and had 1 inpatient or 2 outpatient claims with GI NET, identified by International Classification of Diseases, 9th Revision, Clinical Modification codes. Incidence was calculated as number of patients with NET who were disease-free for 2 years prior, divided by number of enrollees and reported as per million person-years (PMPY). Prevalence was calculated as the number of GI NET patients divided by the number of enrollees per year. The annual number of patients with GI NET ranged from 2,014 to 3,413 in MarketScan and 1,436 to 2,336 in PharMetrics. Incidence increased from 2011 to 2014: 67.0 to 79.1 PMPY in MarketScan and 47.4 to 58.2 PMPY in PharMetrics. Incidence increased by 24.3% in females and 10.7% in males in MarketScan, and by 17.6% in females and 29.3% in males in PharMetrics. Incidence increased with age and was highest in the 45 to 54 and 55 to 64 age groups. Prevalence increased from 77.9 to 131.2 per million per year (MarketScan) and 50.8 to 108.9 (PharMetrics) from 2009 to 2014. Prevalence was generally higher in females than males and highest in 55 to 64 year olds. These increases may be due to better diagnostics, increased awareness of NET among clinicians and pathologists, and/or actual increase in disease. Clinicians may see GI NET with increasing frequency and should become more familiar with its presentation and treatment. GI = gastrointestinal; ICD-9-CM = International Classification of Diseases, 9th Revision, Clinical Modification; NET = neuroendocrine tumor; PMPY = per million person-years; SEER = Surveillance, Epidemiology, and End Results.


Mechanism underlying oxidative stress-mediated lipotoxicity: exposure of J774.2 macrophages to triacylglycerols facilitates mitochondrial reactive oxygen species production and cellular necrosis.
The aim of this study was to elucidate death pathways in macrophages resulting from exposure to triacylglycerols (TG), mechanisms which may be relevant to the development of atherosclerosis. A commercial TG emulsion (lipid emulsion, LE; 0.1-1.5 mg lipids/ml) was added to J774.2 cells in culture. Within the first 24 h after TG treatment, cellular reactive oxygen species (ROS) levels were strongly elevated and basal caspase-3 activity was attenuated. In contrast, after 48 h, ROS production was arrested. TG-mediated ROS production was demonstrated to be via mitochondrial complex 1 of the electron-transfer chain since the inhibitor of complex 1 rotenone significantly attenuated the cellular ROS levels in TG-treated cells. The TG effect culminated in cell death, with no caspase-3 activation. We therefore evaluated the effect of TG on apoptotic cells showing high caspase activity. TG induced elevated ROS levels and suppressed caspase-3 in apoptotic cells pretreated for 24 h with cycloheximide. Dual staining with propidium iodide and Annexin V followed by flow cytometric analysis showed that TG facilitated cell death with clear necrotic characteristics. To elucidate whether the necrotic cell death process is indeed oxidant dependent, antioxidant protection was studied. Treatment with N-acetylcysteine (NAC) (0.5 mM), ascorbic acid (0.5 mM), and resveratrol (0.2 mM) protected against the TG lipotoxic effect, while, surprisingly, lipophilic antioxidants did not. The combination of NAC, ascorbic acid, and resveratrol, each at much lower concentrations, had a synergistic protective effect. In conclusion, we show here for the first time that exposure to TG can directly regulate lipotoxicity in macrophages by inducing mitochondria-mediated prolonged oxidative stress; this, in turn, can inactivate the apoptotic caspase system, resulting in necrotic cell death which can be prevented by specific antioxidants.


Isolation and identification of phenolic substances from the fungus Penicillium spinulosum.
Penicillium spinulosum grown in a Czapek-Dox medium containing glucose produces two phenolic substances: 4-methyl orcinol (beta-orcinol) and 3-methyl orsellinic acid (beta-orcinolcarboxylic acid). Their isolation and identification are described. They are considered to be precursors of quinoids occuring in aged media and responsible for their red-violet colours. Preliminary results indicate that one of the quinoid compounds may be a diphenoquinone.


Detection of IKKε by immunohistochemistry in primary breast cancer: association with EGFR expression and absence of lymph node metastasis.
IKKε is an oncogenic kinase that was found amplified and overexpressed in a substantial percentage of human breast cancer cell lines and primary tumors using genomic and gene expression analyses. Molecular studies have provided the rational for a key implication of IKKε in breast cancer cells proliferation and invasiveness through the phosphorylation of several substrates. Here, we performed immunohistochemical detection of IKKε expression on tissue microarrays constituted of 154 characterized human breast cancer tumors. We further determined the association with multiple clinicopathological parameters and 5-years overall, disease-free and distant disease free survival. We observed expression of IKKε in 60.4% of the breast cancer tumors. IKKε expression status showed no association with a panel of markers used for molecular classification of the tumors, including ER/PR/HER2 status, or with the molecular subtypes. However, IKKε expression was inversely associated with lymph node metastasis status (p = 0.0032). Additionally, we identified a novel association between IKKε and EGFR expression (p = 0.0011). The unexpected observation of an inverse association between IKKε and lymph node metastasis advocates for larger scale immunohistochemical profiling of primary breast tumors to clarify the role of IKKε in metastasis. This study suggests that breast cancer tumors expressing EGFR and IKKε may be potential targets for drugs aiming at inhibiting IKKε activity or expression.


WT1 expression is inversely correlated with MYCN amplification or expression and associated with poor survival in non-MYCN-amplified neuroblastoma.
Neuroblastoma (NB) is the most common extra cranial solid tumor in childhood and the most frequently diagnosed neoplasm during infancy. A striking feature of this tumor is its clinical heterogeneity. Several tumor progression markers have been delineated so far, among which MYCN amplification, which occurs in about 25% of total NB cases, with the percentage increasing to 30% in advanced stage NB. Although MYCN amplification is strongly correlated with NB of poor outcome, the MYCN status cannot alone predict all cases of poor survival in NB. Indeed NB without MYCN amplification (about 70-80% of NB) are not always favorable. WT1 was initially identified as a tumor suppressor gene involved in the development of a pediatric renal tumor (Wilms' tumor). Here, we describe an inverse correlation between WT1 expression and MYCN amplification and expression. However and most notably, our results show that WT1 gene expression is associated with a poor outcome for patients showing non-MYCN-amplified tumors. Thus WT1 expression is clinically significant in NB and may be a prognostic marker for better risk stratification and for an optimized therapeutic management of NB.


MR imaging in a desmoid tumor of the posterior mediastinum with extension into the abdominal cavity. A case report.
We report on a rare case of desmoid tumor in a 40-year-old man with low back pain and cough. There was no history of previous surgery or trauma. MR imaging revealed a posterior mediastinal mass extending into the abdominal cavity.


Quantification of the curvature and shape of the interventricular septum.
The interventricular septum (IVS) occupies a unique position within the heart, lying between the left (LV) and right (RV) ventricular cavities. Changes in its normal geometry may signify not only abnormalities of the septal myocardium, but also abnormal pressure differences between the LV and RV. Flattening of the IVS has been noted with cross-sectional imaging in association with pulmonary hypertension, but the septal curvature and shape have not previously been measured in three dimensions. This paper describes a method to model the RV surface of the IVS from spatially registered cross-sectional images for measurements of curvature. A smoothing 2D spline surface is constructed through the RV septal surface at regular times during the cardiac cycle, and the principal curvatures, as well as the Gaussian and mean curvatures, shape index, and curvedness, are calculated. Vector and color surface maps and graphs of average curvature and shape indices are constructed. Consistent curvature patterns were observed in four normal subjects. This method of measuring septal geometry can provide potentially useful new information on the effects of RV disease. We examine the problem of describing septal motion, and describe a simple measure of septal curvature that may be of clinical value.


Air Bubbles in the Heart: A Case of Contrast Media Injection-Induced Venous Air Embolism.
Venous air embolism (VAE) is more frequently recognized nowadays with the increased use of computed tomography (CT). It may be detected during or even after intravenous contrast media injection. A wide range of clinical manifestations exist, ranging from an incidental finding in a clinically asymptomatic patient to obstructive shock and circulatory failure. Those found incidentally are usually small and have no significant effect on circulatory physiology. Larger air emboli, however, may be potentially fatal, and therefore it is important to recognize such a phenomenon in the setting of intravenous contrast media injection.


Lifitegrast ophthalmic solution in the treatment of signs and symptoms of dry eye disease: design, development, and place in therapy.
A new topical ophthalmic medication, lifitegrast 5%, was recently approved by the US Food and Drug Administration for use in dry eye patients. Lifitegrast is an integrin antagonist that decreases inflammation on the ocular surface, thereby improving dry eye disease (DED). Through a series of prospective, multicenter, randomized, masked, placebo-controlled studies in >2,000 patients total, lifitegrast was shown to be effective for improvement in both the signs and symptoms of DED. A subsequent study focused on the safety profile of lifitegrast and demonstrated that the majority of adverse events were mild and resolved over time. Lifitegrast is now available for use in clinical practice.


Beyond rhetoric: what we need to know to eliminate disparities.
Racial and ethnic disparities in health care are well documented and can be discussed in 3 broad categories: health system factors, patient-level factors, and patient/provider interaction. Clinicians and others working in health care and related fields are knowledgeable about disparities in health, but the general US population is not. Racial/ethnic disparities are most striking in life expectancy, infant mortality, and lack of health insurance. The inaugural edition of the National Healthcare Disparities Report, due out in 2003, will provide valuable insights into the state of health care in America, including a comprehensive view of disparities in health care. The Agency for Healthcare Research and Quality is conducting and supporting research, data collection, and other initiatives aimed at reducing racial/ethnic disparities in health care. The documented disparities in health care represent a critical opportunity for quality improvement that requires input from all sectors, including policymakers, providers, community leaders, and patients.


The in vivo gastrointestinal absorption in rats of the intact cyclo(L-leucylglycine) dipeptide.
Unanesthetized rats with catheterized portal veins were administered, intragastrically, a saline solution of the diketopiperazine cyclo(L-leucyl-[U-14C]glycine) (cyclo(L-Leu-[14C]Gly)) at a dose of 47.9 nmol. The appearance of this cyclic dipeptide in portal vein plasma was followed chromatographically using a microcolumn of Sephadex G-25 complexed with copper. Further identification was done by thin-layer chromatography. Net absorption was evaluated by the balance method. The intestinal site of maximal absorptive capacity for cyclo(L-Leu-[14C]Gly) was also investigated. The gastric emptying rate was 98% in 15 min. After intragastric administration, cyclo(L-Leu-[14C]Gly) was absorbed (peak at 2.5 min) into the portal vein. The balance method showed that the efficiency of absorption was 94% within the first 10 min and was completed after 20 min. This compound was absorbed intact and remained unmetabolized in the portal vein of the rat and seemed to be absorbed throughout the length of the small intestine. Shortly after administration (1- to 5-min period), the greatest absorption of the diketopiperazine occurred at the level of the duodenum; however, the absorption maximum appeared to move down the gut and after 10 min the highest uptake took place in the jejunum, but never seemed to reach the ileum to a significant degree. Only negligible amounts of the cyclic dipeptide were excreted with the feces. Cyclo(L-Leu-[14C]Gly) is thus an example of a low molecular weight peptide which is rapidly and completely absorbed, after its intragastric administration at low concentration and is enzymatically stable during the process of absorption. In vitro experiments determined that this peptide apparently traverses the intestinal wall passively and does not use the carrier-mediated mechanisms for linear peptides.


Hypertension may affect tooth-supporting alveolar bone quality: a study in rats.
This study evaluates the ligature-induced bone loss (BL) and quality of tooth-supporting alveolar bone in spontaneously hypertensive rats (SHRs) by histometric, histochemical, and immunohistochemical analyses and assesses the effects of lercanidipine on these parameters. Wistar rats and SHRs were assigned to one of the following groups: normotensive rats (n = 15), untreated SHRs (n = 15), and treated SHRs (n = 15). The latter group was treated daily with lercanidipine for 45 days. Two weeks after the beginning of drug administration, the first right mandibular molar received a cotton ligature, whereas the contralateral tooth was left unligated. The following parameters were analyzed in the furcation area of decalcified histologic sections: BL, bone density (BD), number of positive cells for tartrate-resistant acid phosphatase (TRAP+), and expression of receptor activator of nuclear factor-kappa B ligand (RANKL) and osteoprotegerin (OPG). In ligated teeth, no significant differences among groups were found regarding BL, TRAP+ cells, and the ratio of RANKL/OPG+ cells (P >0.05), although the expression of RANKL was decreased in the treated SHR group (P <0.05). Increased BL and decreased BD were observed around unligated teeth of the untreated and treated SHR groups (P <0.05). In the furcation area of the unligated teeth, the untreated SHR group presented a higher number of TRAP+ cells and higher ratio of RANKL/OPG+ cells compared to the other groups. SHRs present harmful alterations in the quality of tooth-supporting bone, independently of inflammation. In addition, the administration of lercanidipine for 45 days decreased the expression of bone-resorption markers.


Early detection and identification of amphizoic amoebae from nasal exudates of a symptomatic case.
A man visited the Out Patient Department of the hospital for Tropical Diseases in February 2004 with low grade fever and severe headache for a week. He had the history of diving in a natural pond 2-3 days before the onset of the disease. A thick bloody mucous was observed from the nasal discharge. Fresh microscopic observation of the exudates in 0.85% sodium chloride revealed numerous active amoeba trophozoites. Two groups of the trophozoites were observed The first group was 10 micro sized amoeba with active directional movement by lobopodia and the second group was 15-30 micro sized amoeba with active multiprogressive movement by filopodia. Few flagellate forms were observed after exflagellation in distilled water and some polygonal cysts were also found. Giemsa' stain was used to differentiate the amoeba trophozoites from the leukocytes. It was concluded that this patient was infected by both Naegleria spp. and Acanthamoeba spp. This is the first report of double infection of free-living amoeba in a symptomatic and non-fatal patient.


Comparison of early aggressive versus nonaggressive fluid resuscitation in acute pancreatitis: a meta-analysis.
Early fluid resuscitation is one of the main therapeutic strategies for acute pancreatitis (AP). This study investigated the effects of early aggressive and nonaggressive hydration on AP. The aim of this meta-analysis is to investigate the differences between aggressive and nonaggressive intravenous fluid resuscitation in AP. This study was based on publicly available data, all of which have been extracted from previous ethically approved studies. Two authors systematically searched PubMed, Embase (via OVID), Web of Science, and Cochrane Library to find all published research before February 2023. In-hospital mortality were set as primary endpoints. This meta-analysis included seven randomized controlled trials (RCTs) and eight cohort studies with 4072 individuals in nonaggressive (n = 2419) and aggressive (n = 1653) hydration groups. The results showed that patients in the nonaggressive group had a lower mortality rate than those in the aggressive hydration group [relative risks (RR), 0.66; p = 0.02]. Subgroup analysis results showed that patients in the nonaggressive hydration group had lower mortality rates in RCTs (RR, 0.39; p = 0.001), studies conducted in Eastern countries (RR, 0.63; p = 0.002), and studies with severe pancreatitis (RR, 0.65; p = 0.02). In addition, the nonaggressive hydration group had lower rates of infection (RR, 0.62; p < 0.001), organ failure (RR, 0.65; p = 0.02), and shock (RR, 0.21; p = 0.02), as well as a shorter hospital stay (weighted mean difference, -1.63; p = 0.001) than the aggressive hydration group. Early nonaggressive fluid resuscitation is associated with lower mortality, lower risk of organ failure and infection, and shorter hospital stays than aggressive fluid resuscitation. CRD42023396388.


Rapid proteomic remodeling of cardiac tissue caused by total body ionizing radiation.
Accidental nuclear scenarios lead to environmental contamination of unknown level. Immediate radiation-induced biological responses that trigger processes leading to adverse health effects decades later are not well understood. A comprehensive proteomic analysis provides a promising means to identify and quantify the initial damage after radiation exposure. Early changes in the cardiac tissue of C57BL/6 mice exposed to total body irradiation were studied, using a dose relevant to both intentional and accidental exposure (3 Gy gamma ray). Heart tissue protein lysates were analyzed 5 and 24 h after the exposure using isotope-coded protein labeling (ICPL) and 2-dimensional difference-in-gel-electrophoresis (2-D DIGE) proteomics approaches. The differentially expressed proteins were identified by LC-ESI-MS-MS. Both techniques showed similar functional groups of proteins to be involved in the initial injury. Pathway analyses indicated that total body irradiation immediately induced biological responses such as inflammation, antioxidative defense, and reorganization of structural proteins. Mitochondrial proteins represented the protein class most sensitive to ionizing radiation. The proteins involved in the initial damage processes map to several functional categories involving cardiotoxicity. This prompts us to propose that these early changes are indicative of the processes that lead to an increased risk of cardiovascular disease after radiation exposure.


Bilateral myofascial trigger points and pressure pain thresholds in the shoulder muscles in patients with unilateral shoulder impingement syndrome: a blinded, controlled study.
To identify the presence of myofascial trigger points (TrPs) and pressure pain threshold (PPT) levels in the shoulder muscles of both involved and uninvolved sides in patients with unilateral shoulder impingement syndrome (SIS). Twenty-seven patients with SIS and 20 matched control patients participated in this study. TrPs of 10 shoulder muscles and 8 PPTs, including tibialis anterior PPT, were assessed. SIS group showed a greater number of TrPs (t=-2.697; P=0.010) than the control group. The muscles of the uninvolved side of the SIS group also presented some active TrPs. PPTs showed small differences between involved and uninvolved sides of patients with SIS and higher differences between both sides of the SIS group and dominant side of controls although with significant difference only in the supraspinatus PPT (F=3.239; P=0.045). The muscle PPTs of the patients presenting TrPs in each muscle of the involved side were lower than the PPTs of the patients without TrPs in the same muscle for both involved and uninvolved sides with few significant differences. The high number of TrPs in the involved side of patients with SIS suggests the presence of peripheral sensitization. The results reject the presence of central alterations. Finally, the patients with unilateral SIS may present bilateral deficits related to myofascial pain.


Microleakage of cervical cavities restored with flowable composites.
To investigate the microleakage of cervical cavities restored with flowable composites in conjunction with an all-in-one adhesive system (AQ Bond) and an experimental two-step self-etching primer system (ABF) after thermocycling or flexural load cycling. 180 wedge-shaped cervical cavities on the labial surfaces of bovine incisors were treated with AQ Bond or ABF according to the manufacturers' instructions. The treated cavities were filled with one of three flowable composites (AElite Flo, Metafil Flo or Protect Liner F). Ten of 30 specimens for each group were immersed in 0.5% basic fuchsin solution immediately after finishing of the restorations. Specimens to be subjected to thermocycling (5-60 degrees C, 15 seconds dwell time, 5000 cycles) or to flexural load cycling (approximately 0.5 mm labio-lingual displacement at the incisal edge, 10,000 cycles, 1 Hz) prior to immersion in the dye were also prepared. After 24-hour storage in the dye solution, the teeth were sectioned longitudinally through the center of the restorations, and the degrees of dye penetration scored. The microleakage scores of a hybrid composite (Clearfil AP-X) obtained from our previous study were used for comparison. The data were analyzed with the Kruskal-Wallis test and the Mann-Whitney U-test (P < 0.05). No significant differences in the microleakage patterns and scores were found among the flowable composites. On the other hand, significant differences in the microleakage patterns and scores were observed between the flowable and the hybrid composites. Thermocycling caused deterioration of marginal integrity, and the flowable composites showed more microleakage than the hybrid composite. In contrast, flexural load cycling did not cause deterioration of the marginal integrity when the cavities were filled with the flowable composites. Statistical analysis also revealed that the adhesive systems played a large role in the microleakage patterns.


Function-stabilizing mechanism of plasminogen activator inhibitor type 1 induced upon binding to alpha1-acid glycoprotein.
Recently, we found that alpha(1)-acid glycoprotein (AGP), one of the major acute-phase proteins, forms a function-stabilizing complex with plasminogen activator inhibitor 1 (PAI-1). In this study we describe the mechanism by which AGP, as well as its recombinant fragment AGP(118)(-)(201), interacts exclusively with the active form of PAI-1 and stabilizes its conformation. The binding domain of PAI-1 for AGP was initially mapped by antibodies reacting with the well-defined PAI-1 epitopes and then verified in binding assays utilizing a library of PAI-1 mutants. The latter consisted of PAI-1 molecules with individual, tandem, or grouped mutations in the epitope region of MA-55F4C12, MA-33B8, MA-33H1F7, MA-44E4, and MA-8H9D4. Solid-phase binding experiments showed that only MA-8H9D4 did not bind to the PAI-1/AGP complex, indicating that its epitope is hidden upon binding of PAI-1 to AGP. Consistently, only PAI-1 mutants with substitutions in the region of R300-D305, constituting the MA-8H9D4 epitope, showed a lack of binding or severe deficit in both the capacity and affinity of binding to AGP. These results support a location of the binding site close to the epitope within the segment connecting the regions hI with S5A. In conclusion, our present data suggest that AGP binding stabilizes the active conformation of PAI-1 by restricting the movement of beta-sheet A and thereby preventing insertion of the reactive center loop.


Targeting skeletal muscle tissue oxygenation (StO2) in adults with severe sepsis and septic shock: a randomised controlled trial (OTO-StS Study).
Evaluation of the ratio of oxyhaemoglobin to total haemoglobin in skeletal muscle (StO2) using near-infrared spectroscopy may aid in the monitoring of patients with sepsis. This study assessed the benefits and risks of targeting StO2 in adults with severe sepsis or septic shock. A European randomised controlled trial was performed on two parallel groups. Five intensive care units (ICU) in France, Greece, Spain and Germany were used for the study. A total of 103 adults with severe sepsis or septic shock on ICU admission were randomised (54 subjects in the experimental arm and 49 subjects in the control arm). Haemodynamic management using an algorithm that was adapted from the 2004 Surviving Sepsis Campaign guidelines with (experimental arm) or without (control arm) targeting an StO2 value greater than 80% at a minimum of two different sites. The primary outcome was a composite: 7-day all-cause mortality or worsening of organ function, defined as a positive difference in Sepsis-related Organ Failure Assessment (SOFA) score between day 7 and randomisation (ie, delta SOFA >0). Secondary endpoints: 30-day mortality, duration of mechanical ventilation and vasopressor therapy up to 30 days from randomisation. The study ended prematurely due to lack of funding after enrolment of 103/190 patients. Eighteen patients (33.3%) in the experimental arm and 14 (28.6%, P=0.67) in the control arm died or exhibited delta SOFA >0 on day 7. The mean number of days on mechanical ventilation was 12.2±10.6 in the experimental group and 7.6±7.9 in the control group (P=0.03). Thirty-one (57%) patients in the experimental arm and 14 (29%) patients in the control arm received red cells by day 7 (P=0.01). Despite the limitation related to premature termination, this study provides no data to support the routine implementation of resuscitation protocols incorporating StO2 >80% at two or more muscle sites as a target. StO2-guided therapy may be associated with prolonged use of mechanical ventilation and an increased number of red blood cell transfusions. NCT00167596; Results.


The effect of vitamin E on basic fibroblast growth factor level in human fibroblast cell culture.
Basic fibroblast growth factor (bFGF) is angiogenic and effective in down-regulating excess collagen production. The aim of this study is to evaluate the effectiveness of vitamin E (Tocotrienol Rich Fraction) in altering the level of bFGF, a cytokine involved in the scar formation process. In this model, normal human fibroblasts were treated with various concentrations of vitamin E at different time frames. The levels of bFGF were determined by Enzyme-Linked Immunosorbant Assay (ELISA). This study demonstrated that Tocotrienol Rich Fraction (TRF) stimulated bFGF production by fibroblast and postulate that vitamin E may decrease aberrant scar formation.


Potential Feasibility of an Online Hypnosis Intervention for Women with Persistent Pelvic Pain.
This study aimed to examine the potential feasibility of an online hypnotic intervention for women with persistent pelvic pain. The secondary aim was to explore the effect of the hypnosis intervention on anxiety, depression, pain severity, coping, pain catastrophizing, and pain disability in comparison to a no-intervention control. Twenty women with persistent pelvic pain completed assessment questionnaires and were recruited from a variety of social media sites related to persistent pelvic pain and randomized to either control or hypnotic intervention groups. The intervention group completed a 7-week online hypnotic intervention. Results found a 30% dropout rate and modest compliance (90%-40%) with practice of audio recordings. Comments from the 7 participants who completed the hypnosis intervention indicated it was acceptable. Significant reductions in screening measures of anxiety and depression were found; however, there were no significant effects shown for pain severity, avoidant coping, pain catastrophizing, or pain disability. The intervention is potentially feasible, but further refinement and optimization is needed to increase retention, compliance, and potential effects.


Autoimmune Pulmonary Alveolar Proteinosis Complicated by Myelodysplastic Syndrome: A Case Report.
Pulmonary alveolar proteinosis (PAP) is characterized by an abnormal surfactant accumulation in peripheral air spaces. Autoimmune PAP (APAP) results from macrophage dysfunction caused by anti-granulocyte-macrophage colony-stimulating factor (GM-CSF) autoantibodies, and the presence of antibodies more than the cutoff value is specific for APAP. In contrast, secondary PAP (SPAP) does not require anti-GM-CSF autoantibodies and is complicated by other diseases, including myelodysplastic syndrome (MDS). A 73-year-old man with anemia and thrombocytopenia was diagnosed with APAP and MDS simultaneously. The measurement of serum anti-GM-CSF autoantibodies is important for the correct diagnosis and management of PAP, even with an established diagnosis of underlying SPAP-suggestive disease.


Evaluation of the effect of soybean milk and soybean milk peptide on bone metabolism in the rat model with ovariectomized osteoporosis.
We have reported that soybean milk is an excellent source for increasing bone mineral density (BMD) and mechanical bone strength. However, it is not known what kind of components in soybean milk affect bone metabolism. Consequently, the purpose of this study is to find the effective components in soybean milk on bone metabolism. It might be some peptide in soybean milk. Therefore, in this study the soybean milk was separated into two different preparations according to molecular weight: a high-molecular-weight soybean milk, and a low-molecular-weight soybean milk. Then, the effect of the peptides in soybean milk on bone metabolism was examined. After producing the experimental osteoporotic model rats, they were divided into four groups. The BMD and the mechanical bone strength of the three experimental groups, whose diet contained a soybean milk, a high-molecular soybean milk, or a low-molecular soybean milk (soybean milk peptide) were significantly higher than those of the control group. Moreover, the intestinal Ca absorption for the three experimental groups was significantly increased. From these results, the peptides in the soybean milk are effective for the acceleration of the intestinal Ca absorption. It is possible to assume that the mechanism for increasing the BMD and the mechanical strength in the three experimental groups was due to increasing the intestinal Ca absorption by alimenting the soybean milk, the high-molecular soybean milk or the low-molecular soybean milk.


Tourniquet Deflation Prior to 20 Minutes in Upper Extremity Intravenous Regional Anesthesia.
Bier blocks, or intravenous regional anesthesia (IVRA), are a method of anesthesia for upper extremity surgeries. This study reports our experience with tourniquet deflation prior to 20 minutes with upper extremity IVRA. This study was designed as a retrospective cohort analysis. Records, including intraoperative and immediate postoperative anesthesia notes, of 430 patients who underwent IVRA with an upper extremity Bier block and a corresponding tourniquet time of less than 20 minutes were reviewed. Patient demographics, procedure(s) performed, American Society of Anesthesiologists scores, volume of lidocaine used in Bier block, tourniquet time, and any complications were recorded. This cohort consisted of 127 males and 303 females. The 3 most common procedures performed were carpal tunnel release (315), trigger finger release (47), and excision of masses (34). The average tourniquet time for this cohort was 16 minutes (range, 9-19 minutes), and the average volume of lidocaine (0.5% plain) injected was 44 mL (range, 30-70 mL). A tourniquet time of 17 minutes or less was observed in 339 patients, and 170 patients had tourniquet times of 15 minutes or less. Five complications were recorded: intraoperative vomiting, mild postoperative nausea/vomiting, severe postoperative nausea and vomiting, and transient postoperative hypotension that responded to a fluid bolus. No major complications were observed in our cohort of upper extremity IVRA and tourniquet times of less than 20 minutes. Several variables play a role in the safety of upper extremity IVRA.


Persistent tachycardia within isolated pulmonary veins during atrial fibrillation ablation.
During circumferential pulmonary vein (PV) isolation for ongoing atrial fibrillation (AF), distinguishing passive conduction to the pulmonary vein (PV) from rapid PV arrhythmia in the isolated PV is difficult. Hence, the purpose of this study is to investigate both the feasibility of distinguishing the PV tachycardia after circumferential PV isolation and the electrophysiological characteristics of these tachycardia. Among 178 consecutive patients who underwent circumferential PV isolation during ongoing AF, fibrillatory PV converted to a regular cycle length PV tachycardia independent of the atrial rhythm (=independent PV tachycardia) in 13 PVs among 12 (7%) patients. We classified independent PV tachycardia according to 3 different atrial rhythms: sinus rhythm (type 1, n = 2), atrial tachycardia (type 2, n = 4), and AF (type 3, n = 6). independent PV tachycardia was observed in 3 right PV and 10 left PV (P = 0.0864). There were 10 mappable independent PV tachycardia, in which 8 were focal and 2 were macroreentrant tachycardia. i-PVT can be diagnosed in a small number of patients who underwent circumferential PV isolation during AF. The main mechanism or independent PV tachycardia was focal tachycardia mainly in the left PV.


Urea in dry-rolled corn diets: finishing steer performance, nutrient digestion, and microbial protein production.
In Exp. 1, 88 yearling steers (332 kg) were fed dry-rolled corn finishing diets to evaluate effects of dietary urea level on performance and carcass characteristics. Diets contained 0, .5, 1.0, or 1.5% urea (DM basis), which supplied all supplemental N, and 10% chopped prairie hay. Gains (P = .10) and gain efficiency (G/F; P < .05) were increased by .5% urea, with little improvement by additional urea. Regression analysis estimated optimal dietary urea at .9% of DM for ADG and G/F. Fat thickness (P < .05) and yield grade (P < .10) increased linearly with dietary urea level. In Exp. 2, four ruminally and duodenally cannulated steers (557 kg) were fed the diets used in Exp. 1 to evaluate effects of dietary urea on site and extent of digestion. True ruminal OM and starch digestion were increased 25 and 37%, respectively, by .5% urea, but higher urea levels did not differ from .5%. Flows of total N and microbial N to the duodenum were not affected by urea level. In Exp. 3, 100 yearling steers (347 kg) were fed dry-rolled corn finishing diets that contained 10% alfalfa hay as the dietary roughage to evaluate effects of dietary urea level on performance and carcass characteristics. Urea levels were 0, .35, .70, 1.05, or 1.40% urea (DM basis), with no other supplemental N provided. Dry matter intake (P = .10), ADG (P < .05), and G/F (P < .05) increased with intermediate concentrations of urea but decreased with the highest concentration. Regression analysis indicated that the optimal dietary urea level was .5% of DM for ADG and G/F. Urea increased dietary energy utilization but not metabolizable protein supply.


Sex differences in schizophrenia, bipolar disorder, and post-traumatic stress disorder: Are gonadal hormones the link?
In this review, we describe the sex differences in prevalence, onset, symptom profiles, and disease outcome that are evident in schizophrenia, bipolar disorder, and post-traumatic stress disorder. Women with schizophrenia tend to exhibit less disease impairment than men. By contrast, women with post-traumatic stress disorder are more affected than men. The most likely candidates to explain these sex differences are gonadal hormones. This review details the clinical evidence that oestradiol and progesterone are dysregulated in these psychiatric disorders. Notably, existing data on oestradiol, and to a lesser extent, progesterone, suggest that low levels of these hormones may increase the risk of disease development and worsen symptom severity. We argue that future studies require a more inclusive, considered analysis of gonadal steroid hormones and the intricacies of the interactions between them, with methodological rigour applied, to enhance our understanding of the roles of steroid hormones in psychiatric disorders. LINKED ARTICLES: This article is part of a themed section on The Importance of Sex Differences in Pharmacology Research. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v176.21/issuetoc.


Low serum thyroxine on initial newborn screening is associated with intraventricular hemorrhage and death in very low birth weight infants.
Transient hypothyroxinemia (TH) of prematurity has been correlated with poor neurodevelopmental outcome. However, the relationship between thyroid function and neonatal mortality and brain injury has not been described. To investigate the relationship between thyroid function and neonatal outcome. Review of infants weighing <1500 grams admitted to a single level III newborn intensive care unit (n = 342). Serum total T4 values of initial newborn screening of infants dying before hospital discharge were compared with those of surviving infants. Total T4 values from infants with and without intraventricular hemorrhage (IVH) and periventricular leukomalacia (PVL) also were compared. T4 values strongly correlated with gestational age (r = .56). Overall, 289 (85%) of 342 infants had TH. None of the infants had true congenital hypothyroidism. T4 values of infants with cystic PVL (n = 15) were not statistically different from those for infants who did not develop cystic PVL. Infants with IVH (n = 58) had a lower T4 value than did infants who did not develop IVH (5.4 +/- 3.4 microg/dL vs 7.8 +/- 3.6 microg/dL). Infants who died before hospital discharge (n = 24) had a lower T4 value than did infants discharged to home (3.4 +/- 2.2 vs 7.9 +/- 3.7 microg/dL). After controlling for potential confounding variables, T4 value remained associated with an increased odds of IVH (odds ratio: 1.2; 95% confidence interval: 1.05 to 1.4) and mortality (odds ratio: 2.3; 95% confidence interval 1.6 to 3.4). In our population of very low birth weight infants, TH has an incidence of 85%. Very low T4 values on initial newborn screening are associated with increased odds of death and IVH. Additional investigation is needed to determine whether low serum thyroxine level contributes to IVH and neonatal death or whether it is simply an associated factor.


Stingless Bees as Alternative Pollinators of Canola.
Alternative pollinators can ensure pollination services if the availability of the managed or most common pollinator is compromised. In this study, the behavior and pollination efficiency of Apis mellifera L. and two species of stingless bees, Plebeia emerina Friese and Tetragonisca fiebrigi Schwarz, were evaluated and compared in flowers of Brassica napus L. 'Hyola 61'. A. mellifera was an efficient pollinator when collecting nectar because it effectively touched the reproductive organs of the flower. In contrast, stingless bees were efficient pollinators only when collecting pollen. The number of pollen grains deposited on the stigma after a single visit by worker bees of the three species was greater than the number of grains resulting from pollination without the bee visits. On average, the three species deposited enough pollen grains to fertilize all of the flower ovules. A. mellifera and P. emerina had similar pollination efficiency because no significant differences were observed in the characteristics of the siliques produced. Although T. fiebrigi is also an effective pollinator, the seed mass produced by their pollination was lower. Native bees promoted similar rates of fruit set compared with A. mellifera. Thus, P. emerina has potential to be used for pollination in canola crops.


Mycobacterium szulgai infection in the flexor sheath of the right index finger in an immunocompetent patient.
A 53-year-old woman was identified with Mycobacterium szulgai infection in the flexor sheath of the right index finger. Tissue was debrided at operation, and the patient was successfully treated with appropriate antimicrobials. M. szulgai is a rare cause of non-tubercular mycobacterium infection worldwide, and there are currently no clear guidelines on diagnosis and management. This is the first case reporting M. szulgai infection in the flexor sheath of the right index finger of a non-immunocompromised patient in the UK.


Electrophysiology and Innervation of the Photosensitive Epistellar Body in the Lesser Octopus Eledone cirrhosa.
The innervation and responses to light of the cephalopod epistellar body were investigated in preparations isolated from the stellate ganglia of the lesser or northern octopus, Eledone cirrhosa. Extracellular generator potentials in response to flashes of light were recorded from these photosensitive vesicles, with the amplitude of the response being found to be dependent upon the intensity of the flash and the level of ambient illumination. Intracellular recordings from photoreceptor cells of the epistellar body showed that they had resting potentials of about -49 +/- 7 mV (mean +/- SD, n = 43) and were depolarized by flashes of white, but not red (>650 nm) light. The evoked depolarization consisted of a transient component, followed by a steady plateau in which the amplitude of the depolarization was well correlated with the log of the stimulus intensity. The evoked depolarizations induced action potentials in the photoreceptor cells, with the frequency of firing being well correlated with the stimulus intensity. The morphologies of individual photoreceptor cells were visualized by intracellular injections of the fluorescent dye Lucifer yellow, and the path of the epistellar nerve across the stellate ganglion, into the pallial nerve, toward the brain was traced using the lipophilic dye Di-I. This pathway was confirmed physiologically by recording light-evoked responses from the cut end of the pallial nerve.


High-Performance Li-S Batteries with a Minimum Shuttle Effect: Disproportionation of Dissolved Polysulfide to Elemental Sulfur Catalyzed by a Bifunctional Carbon Host.
A long cycle-life Li-S battery (both the coin cell and pouch cell) is reported with minimum shuttle effect. The performance was achieved with a bifunctional carbon material with three unique features. The carbon can catalyze the disproportionation of dissolved long-chain polysulfide ions to elemental sulfur; the carbon can ensure homogeneous precipitation of Li sulfide on the host carbon, and the carbon has a honeycomb porous structure, which can store sulfur better. All the features are demonstrated experimentally and reported in this paper. Few dissolved polysulfides are found by high-performance liquid chromatography in the electrolyte of the Li-S batteries during cycling, and only dissolved elemental sulfur is detected. The unique porous structure of the carbon made from raw silk is revealed by scanning electron microscopy. The N-containing functionalities that were introduced to carbon from the amino acids of raw silk can catalyze the disproportionation of the dissolved Sn2- to solid S8 at the cathode side, thereby mitigating the shuttle effect. In addition, the hierarchical honeycomb porous structures generated by a carbonization process can physically trap high-order lithium polysulfides and sustain the volume change of sulfur. With the synergistic effects of the unique structures and characteristics of the carbon prepared at 800 °C, the sulfur/carbon composite delivers a high reversible capacity of over 1000 mAh g-1 after 100 cycles with a sulfur content of 1.2 mg cm-2 in a pouch cell.


Bone and soft tissue outcomes, risk factors, and complications of implant-supported prostheses: 5-Years RCT with different abutment types and loading protocols.
Data on risk factors and complications after long-term implant treatment is limited. The aims were to evaluate the role of various fixation modes and to analyze complications and risks that affect long-term use of implant-supported partial fixed dental prostheses. Fifty partially edentulous subjects received three Brånemark TiUnite™ implants. Superstructures were attached directly at implant level (IL) or via abutments: machined surface (AM) and an oxidized surface (AOX, TiUnite™). Implants were immediately loaded (test) or unloaded for 3 months (control). Examinations occurred over a 5-year period. Forty-four subjects were re-examined after 5 years. Cumulative survival rates in test and control groups were 93.9% and 97.0%, respectively. Marginal bone loss (MBL; Mean [SEM]) was significantly lower at superstructures connected to AM (1.61 [0.25] mm) than at sites with no abutment IL (2.14 [0.17] mm). Peri-implantitis occurred in 9.1% of subjects and in 4.0% of implants. Multiple linear regression indicated that increased probing pocket depth (PPD), periodontal disease experience, deteriorating health, and light smoking (≤10 cigarettes/day) predict greater MBL, whereas increased buccal soft tissue thickness and higher ISQ predict lower MBL. The results show that MBL was influenced by the connection type. A machined abutment, instead of connecting the superstructure directly at the implant level, was beneficial. The following factors influenced MBL: PPD, periodontal disease experience, deteriorating health, light smoking, buccal soft tissue thickness, and ISQ. The results on peri-implantitis underscore the need for long-term maintenance care. Further, the abutment material surface properties constitute additional target for strategies to minimize MBL.


Cell Signaling Pathways Involved During Invasion and Syncytialization of Trophoblast Cells.
Implantation involves an extensive cross talk between the trophoblast cells and the receptive endometrium through embryonic as well as endometrial-derived factors that regulate the invasion and migration of trophoblast cells and also syncytia formation. Any aberration in this highly regulated process may lead to pregnancy complications such as preeclampsia, intrauterine growth restriction, or even pregnancy failure. How various cytokines and growth factors act by activating various cell signaling pathways leading to the expression of the effector molecules have been reviewed, which control invasion and migration of trophoblast cells and syncytialization. The gaps in our current understanding of the various signaling pathways, activated by different cytokines/growth factors, their possible cross talk for optimized effector function(s), and future prospects in this field have been discussed.


Adult smoking in the home environment and children's IQ.
In a sample of 3- and 5-yr.-old children, smoking in the home was found to be significantly and inversely related to IQ. Children of normal birth weight and without neurological impairment had been enrolled in a longitudinal study of child development. Analyses were conducted with sex, ethnicity, socioeconomic status, educational stimulation in the home, day care, and mother's intelligence controlled. Significant results were obtained for scores on the Peabody Picture Vocabulary Test-Revised at age three years and on the major Stanford-Binet Fourth Edition scales at ages three and five years. All effects were for the mother, not the father, smoking in the home.


Iliac bone cysts adjacent to the sacroiliac joint: an unusual cause of sacroiliac pain.
The aim of this study was to describe cystic bone lesions involving the sacroiliac region of the iliac bone as a rare cause of sacroiliac joint-related pain. The study included 9 patients with benign cystic bone lesion in Zone 1 according to Enneking and Dunham with a minimum of 2 years follow-up. Detailed radiological examination was performed using magnetic resonance imaging or computed tomography. Extended curettage, adjuvant treatment with phenol and thermal cauterization and bone grafting with auto/allografts were performed. Patients were analyzed for age of onset, side of involvement, clinical and radiological findings, tumor stage, complications and clinical/radiological findings at the final follow-up. Female to male ratio was 4 to 5. Average age at the time of diagnosis was 40.3 (range: 27 to 54) years. Average diameter of the lesion was 6.6 (range: 4 to 11) cm. Superficial infection was detected in one patient and hypoesthesia around the site of incision in two. Clinical improvement in pain and limp was reported in all patients. No radiological recurrence was detected after an average follow-up time of 30.7 (range: 21 to 40) months. Benign tumor-like cystic lesions should be kept in mind in the differential diagnosis of sacroiliac joint-related pain. Such lesions can be safely and effectively managed with intralesional curettage, local adjuvant methods and bone grafting.


Illuminating dynamic neutrophil trans-epithelial migration with micro-optical coherence tomography.
A model of neutrophil migration across epithelia is desirable to interrogate the underlying mechanisms of neutrophilic breach of mucosal barriers. A co-culture system consisting of a polarized mucosal epithelium and human neutrophils can provide a versatile model of trans-epithelial migration in vitro, but observations are typically limited to quantification of migrated neutrophils by myeloperoxidase correlation, a destructive assay that precludes direct longitudinal study. Our laboratory has recently developed a new isotropic 1-μm resolution optical imaging technique termed micro-optical coherence tomography (μOCT) that enables 4D (x,y,z,t) visualization of neutrophils in the co-culture environment. By applying μOCT to the trans-epithelial migration model, we can robustly monitor the spatial distribution as well as the quantity of neutrophils chemotactically crossing the epithelial boundary over time. Here, we demonstrate the imaging and quantitative migration results of our system as applied to neutrophils migrating across intestinal epithelia in response to a chemoattractant. We also demonstrate that perturbation of a key molecular event known to be critical for effective neutrophil trans-epithelial migration (CD18 engagement) substantially impacts this process both qualitatively and quantitatively.


Integrating Clinical Probability into the Diagnostic Approach to Idiopathic Pulmonary Fibrosis: An International Working Group Perspective.
Background: When considering the diagnosis of idiopathic pulmonary fibrosis (IPF), experienced clinicians integrate clinical features that help to differentiate IPF from other fibrosing interstitial lung diseases, thus generating a "pre-test" probability of IPF. The aim of this international working group perspective was to summarize these features using a tabulated approach similar to chest HRCT and histopathologic patterns reported in the international guidelines for the diagnosis of IPF, and to help formally incorporate these clinical likelihoods into diagnostic reasoning to facilitate the diagnosis of IPF. Methods: The committee group identified factors that influence the clinical likelihood of a diagnosis of IPF, which was categorized as a pre-test clinical probability of IPF into "high" (70-100%), "intermediate" (30-70%), or "low" (0-30%). After integration of radiological and histopathological features, the post-test probability of diagnosis was categorized into "definite" (90-100%), "high confidence" (70-89%), "low confidence" (51-69%), or "low" (0-50%) probability of IPF. Findings: A conceptual Bayesian framework was created, integrating the clinical likelihood of IPF ("pre-test probability of IPF") with the HRCT pattern, the histopathology pattern when available, and/or the pattern of observed disease behavior, into a "post-test probability of IPF." The diagnostic probability of IPF was expressed using an adapted diagnostic ontology for fibrotic interstitial lung diseases. Interpretation: The present approach will help incorporate the clinical judgment into the diagnosis of IPF, thus facilitating the application of IPF diagnostic guidelines and, ultimately improving diagnostic confidence and reducing the need for invasive diagnostic techniques.


Diagnostic Utility of UroVysion Combined With Conventional Urinary Cytology for Urothelial Carcinoma of the Upper Urinary Tract.
We prospectively evaluated the utility of UroVysion in urothelial carcinomas of the upper urinary tract (UCUUTs). Ninety patients who received nephroureterectomy for UCUUT were enrolled. We performed urinary cytology and UroVysion before nephroureterectomy. We also performed the assays on 23 volunteers without a history of urothelial carcinoma. Seventy-five high-grade urothelial carcinomas (HGUCs), 10 low-grade urothelial carcinomas, and five other conditions were enrolled. Sensitivity, specificity, positive predictive value, and negative predictive value for HGUC detection by urinary cytology were 28.0%, 100.0%, 100.0%, and 31.6%, respectively; for detection by fluorescence in situ hybridization, these values were 60.0%, 84.0%, 93.8%, and 41.2%, respectively. UroVysion detected the only deletion of 9p21 in eight of 23 samples negative for HGUC by urinary cytology and in three of 23 volunteers. Combining urinary cytology and UroVysion can improve the diagnostic accuracy of UCUUT. Caution is advised in diagnosing UCUUT based only on deletion of 9p21.


Executive dyscontrol in normal aging: normative data, factor structure, and clinical correlates.
Although there is ample evidence of frontal system dysfunction in old age, the clinical significance of these impairments has not been well studied. In this article, we examine the factor structure of putative executive measures in a sample of well elderly subjects. Three stable factors emerged, but only one was associated with measures of functional status. This factor was most strongly associated with relatively simple bedside executive measures that might prove useful in dementia screening. In contrast, a second factor, dominated by the Wisconsin Card Sorting Task, was weakly associated with disability. These data suggest that certain executive measures may be more relevant to functional outcomes, and hence dementia case finding, than others. Moreover, associations with functional status should not be casually extrapolated from regional frontal clinical correlations, particularly with the dorsolateral prefrontal cortex.


Inhibitors of HGFA, Matriptase, and Hepsin Serine Proteases: A Nonkinase Strategy to Block Cell Signaling in Cancer.
Hepatocyte growth factor activators (HGFA), matriptase, and hepsin are S1 family trypsin-like serine proteases. These proteases proteolytically cleave the single-chain zymogen precursors, pro-HGF (hepatocyte growth factor), and pro-MSP (macrophage stimulating protein) into active heterodimeric forms. HGF and MSP are activating ligands for the oncogenic receptor tyrosine kinases (RTKs), c-MET and RON, respectively. We have discovered the first substrate-based ketothiazole inhibitors of HGFA, matriptase and hepsin. The compounds were synthesized using a combination of solution and solid-phase peptide synthesis (SPPS). Compounds were tested for protease inhibition using a kinetic enzyme assay employing fluorogenic peptide substrates. Highlighted HGFA inhibitors are Ac-KRLR-kt (5g), Ac-SKFR-kt (6c), and Ac-SWLR-kt (6g) with K is = 12, 57, and 63 nM, respectively. We demonstrated that inhibitors block the conversion of native pro-HGF and pro-MSP by HGFA with equivalent potency. Finally, we show that inhibition causes a dose-dependent decrease of c-MET signaling in MDA-MB-231 breast cancer cells. This preliminary investigation provides evidence that HGFA is a promising therapeutic target in breast cancer and other tumor types driven by c-MET and RON.


Snare technique of vascular transposition for microvascular decompression--technical note.
Recurrence of trigeminal neuralgia (TN) or hemifacial spasm (HFS) after microvascular decompression (MVD) is not rare. The prosthesis material eventually adheres to the neurovascular structures and again transmits arterial pulsation to the nerve. A snare ligature technique using a Gore-Tex tape can be used for the transposition of the offending artery. No prosthesis is necessary once the transposition is complete. This technique requires introduction of either Gore-Tex tape or thread around the artery and suture over the petrous dura, so an adequate working space as if operating in a shallow basin is essential. Therefore, the osteoplastic craniotomy is a little larger than usual with the scalp flap entirely reflected using a semicircular skin incision. The Gore-Tex tape can be directly snared around the artery and sutured over the petrous dura. If this procedure is difficult, a thread can be attached to both ends of the Gore-Tex tape to pass the tape around the vessel. Seven patients with TN and 13 patients with HFS have undergone this surgery. Although the follow-up period is not yet long enough, there has been no case of recurrence. The present technique for MVD can provide complete and permanent transposition of the offending artery.


Ventilator Management of Bronchopleural Fistula Secondary to Methicillin-Resistant Staphylococcus aureus Necrotizing Pneumonia in a Pregnant Patient with Systemic Lupus Erythematosus.
Managing mechanical ventilation in patient with bronchopleural fistula with coexisting acute respiratory distress syndrome is a challenging situation for the intensivist. We are reporting a case of a pregnant patient with systemic lupus erythematosus on immunosuppressive medications who developed methicillin-resistant Staphylococcus aureus necrotizing pneumonia complicated by bronchopleural fistula and acute respiratory distress syndrome.


[Prediction of ischaemic lesions of the brain in reconstructive operations on internal carotid arteries].
The present study was undertaken to examine the relationship between the level of the intensity of the ultrasonic signal reflected from atherosclerotic plaques (ATP) of carotid arteries and the risk for formation of an ischaemic lesion in the brain matter, detected during diffusion-weighted magnetic resonance imaging (DW-MRI) performed 24 hours after carotid endarterectomy (CEA) or carotid angioplasty and stenting (CAS). Our prospective study included a total of 78 patients presenting with stenosis of the sinus of the interior carotid artery. Of these, 42 patients were subjected to CEA and 36 subjects endured CAS. All patients in the preoperative period underwent ultrasonographic examination with determination of the degree of heterogeneity of ATPs and registration of the values of the intensity of acoustic characteristics of the signal. The condition of the brain matter before and 24 hours after the intervention was assesses by the findings of DW-MRI. None of the patients after the reconstructive intervention during the postoperative period demonstrated any evidence of acute cerebral circulation disorders. DW-MRI carried out 24 hours after the operation revealed acute ischaemia foci (AIF) in 9 (21.4%) patients after CEA and in 18 (50%) patients after CAS (p=0.05). It was revealed that the postoperative occurrence of AIF was related to the intensity of the ultrasonographic signal prior to the operation: in the CEA group patients the postoperative ischaemic foci were associated with high-intensity ultrasonographic signals (more than 25 dB), whereas in the CAS group patients, vice versa - with low-intensity signals (less than 25dB). For CEA, sensitivity and specificity of the preoperative ultrasonographic method of predicting postoperative embolic lesions of the brain appeared to be similar, amounting to 100% each (with the cut-off point of high- and low-intensity signals equaling 25 dB), and for CAS, sensitivity of the method turned out to be 75% and specificity - 100% (with the same cut-off point of 25 dB). A conclusion was drawn that quantitative characteristics of the intensity of an ultrasonographic signal from fragments of atherosclerotic plaques of the sinus of the internal carotid artery made it possible with high probability to predict the risk for the development of AIF in the brain matter after both CEA and CAS and may therefore serve as a reliable criterion for appropriate therapeutic decision-making with the lowest risk of inflicting lesions in a particular case. The threshold cut-off points of high- and low-intensity ultrasonographic signals, as well as their clinical significance are yet to be specified and verified with the growing number of cases.


Analysis of pesticides in dried hops by liquid chromatography-tandem mass spectrometry.
An analytical method was developed for the determination of eleven agrochemicals [abamectin (as B1a), bifenazate, bifenthrin, carfentrazone-ethyl, cymoxanil, hexythiazox, imidacloprid, mefenoxam, pymetrozine, quinoxyfen, and trifloxystrobin] in dried hops. The method utilized polymeric and NH2 solid phase extraction (SPE) column cleanups and liquid chromatography with mass spectrometry (LC-MS/MS). Method validation and concurrent recoveries from untreated dried hops ranged from 71 to 126% for all compounds over three levels of fortification (0.10, 1.0, and 10.0 ppm). Commercially grown hop samples collected from several field sites had detectable residues of bifenazate, bifenthrin, hexythiazox, and quinoxyfen. The control sample used was free of contamination below the 0.050 ppm level for all agrochemicals of interest. The limit of quantitation and limit of detection for all compounds were 0.10 and 0.050 ppm, respectively.


Adapting CBT for youth anxiety: Flexibility, within fidelity, in different settings.
Anxiety disorders are common in youth, associated with impairments in daily functioning, and often persist into adulthood when untreated. Cognitive behavioral therapy (CBT) for youth anxiety is a well-established intervention and has been modified to fit several treatment settings. Despite decades of results supporting the efficacy of CBT, there is a large gap in access to this treatment and a need to consider how it can best be administered flexibly to increase uptake and personalization. We first discuss the core components of treatment for CBT through the lens of the Coping Cat treatment. Next, we review the empirical findings regarding adjustments made for CBT for youth anxiety delivered (a) in schools, (b) in community settings, (c) through telehealth, (d) through online computer programs, and (e) by caregivers at home. In each setting, we provide specific suggestions for how to implement CBT with flexibility while maintaining fidelity.


Hyperprolactinemia and erectile dysfunction.
Hyperprolactinemia from a pituitary adenoma is a rare cause of erectile dysfunction. Men with erectile dysfunction who are found to have a low testosterone level should have a measurement of their prolactin level. Treatment consists of lowering the prolactin level by medication or surgery, or both. Bromocriptine, a dopamine agonist, is efficacious in lowering elevated prolactin levels and can simultaneously shrink these pituitary tumors. With large tumors, transphenoidal surgery may be used to debulk/remove the tumor. Post-treatment prolactin levels can be used to monitor the efficacy of treatment.


In defense of change processes.
Nativist and constructivist approaches to the study of development share a common emphasis on characterizing beginning and end states in development. This focus has highlighted the question of preservation and transformation-whether core aspects of the adult end state are present in the earliest manifestations during infancy. In contrast, a developmental systems approach emphasizes the process of developmental change. This perspective eschews the notions of objective starting and ending points in a developmental progression and rejects the idea that any particular factor should enjoy a privileged status in explaining developmental change. Using examples from motor development and animal behavior, we show how a developmental systems framework can avoid the pitfalls of the long and contentious debate about continuity versus qualitative change.


Histopathologic and Biochemical Evidence for Mitochondrial Disease Among 279 Patients with Severe Statin Myopathy.
Statins have well-known benefits in the prevention of cardiovascular disease, however, 7-29% of patients develop muscle side effects and up to 0.5% develop severe symptoms. Mitochondrial dysfunction has been associated with severe statin-induced myopathy (SM); however, there is a paucity of systematic studies in affected individuals. The goal of this study was to combine clinical and laboratory features with quantitative biochemical and histopathologic studies of skeletal muscle biopsies from SM cases to determine what proportion could be attributed to mitochondrial dysfunction and how many of these had primary respiratory chain defects. A retrospective analysis was performed on patient records derived from 279 SM patients whose muscle biopsies were referred to our clinical diagnostic laboratory for analysis. Clinical, histopathologic and biochemical features were compared with two myopathic control groups unexposed to statins: individuals with idiopathic mitochondrial myopathy (MMP; n = 94) and with unknown metabolic myopathy (UMP; n = 86); normal controls were unavailable for this record review study. More SM patients had significantly elevated plasma CK than in the other two groups (p < 0.01). A subset of SM patients (67 of 279; 24%) had histopathologic and/or electron microscopic (EM) evidence for mitochondrial dysfunction in skeletal muscle; more cases were identified by EM than by histochemical analysis. Of 279 cases, 29 (10%) were confirmed to have respiratory chain defects by biochemical analysis; 4 of these had mitochondrial abnormalities by EM. An additional 20 cases had mitochondrial abnormalities by EM without a biochemical diagnosis. Both primary and secondary mitochondrial dysfunction was found in subsets of SM patients. The fact that respiratory chain defects were not found in most cases with histopathologic mitochondrial abnormalities does not rule out primary mitochondrial disease in these cases, however, it is more likely that secondary effects on mitochondrial structure and function have occurred; molecular analysis may be helpful only in a small number of cases.


[Neurogenic ectopic ossification: a physiatry update].
The first aim of this paper is to present a critical review of the existing literature on neurogenic ectopic ossification. The second aim is to introduce the two papers published in this issue of the journal. In addition, etiopathogenic aspects are described as well as some insights in classical therapies and new therapeutic options which could prove to be useful in the near future.


Micro RNA: an epigenetic regulator of type 2 diabetes.
Type 2 Diabetes is a complex disease with multifactorial pathogenesis. The interplay between genes and lifestyle changes complicates the etiology of the disease. In spite of growing number of attempts to unravel the mechanism of this metabolic disease, the molecular nature of type 2 Diabetes is not fully understood. The discovery of a new class of non-coding RNAs, micro RNAs and their role in regulation of gene expression have paved the way for better understanding of disease pathogenesis. Increasing number of evidences suggest crucial role of miRNAs in insulin resistance and β cell dysfunction, which are the two main features of type 2 Diabetes. This review summarizes the role of miRNA in elicitation and progression of type 2 Diabetes.


Properties of a catalase from a peroxide-resistant mutant of Proteus mirabilis.
A catalase (EC 220.127.116.11) from Proteus mirabilis PR, a mutant with strong resistance to hydrogen peroxide, was purified to homogeneity and compared with catalase from wild-type P. mirabilis. In crude extracts from the mutant, catalase was present as two different entities called A and B, that could be resolved by ion-exchange chromatography. The B form was transformed into A. The pure catalase preparation contained the A form only. This catalase was not found to be different from the wild-type enzyme, considering its molecular weight, subunit composition, isoelectric pH, and reactivity to specific antibodies. Partial proteolytic cleavage of the two bacterial enzymes with four different proteases proceeded at the same rate and produced identical patterns. However, pure catalase from the mutant had a specific activity against H2O2 of 2.7 X 10(7) M-1 X s-1, and its purity index (A406/A280) was 1.12. These values were higher than previously determined for the wild-type enzyme. Furthermore, the mutant catalase was more stable to heat. The results suggest that the purified catalase (A form) differs from the wild-type enzyme and appears to be a more efficient catalase against H2O2. Both enzymes were found to be much more resistant than beef liver catalase to the classically used catalase inhibitor 3-amino-1,2,4-triazole.


[Structural changes in heart at experimental widespread purulent peritonitis].
Structural changes in the heart are studied at an experimental widespread purulent peritonitis. It was established that in 6 hours after initiation of peritonitis in a myocardium the severe disorders of blood circulation, interstitial edema, the phenomena of kariopyknosis, development of systemic toxic damages specifying in high speed at this disease were observed. One of the mechanism of their development is a energy deficiency. The proof of this is destructive changes of cardiomyocytes mitochondria. The comparative analysis of use of metabolic preparations "Citoflavin", containing amber acid, and "Neoton", containing phosphocreatine, for the purpose of pharmacological support of cardiac activity at an experimental widespread purulent peritonitis has revealed high efficiency of the preparation "Citoflavin". It caused more intensive decrease of inflammatory changes in a myocardium, preventing of cardiomyocytes necrobiosis, contribution to preservation of normal structure and growth of quantity of mitochondria.


Utility of Short-Acting Intravenous Insulin Therapy in Preparation of F-18 Fluorodeoxyglucose Positron Emission Tomography Computed Tomography Scan in Cancer Patients Incidentally Detected with High Blood Glucose Levels on the Day of Test.
In diabetic (DM) patients, hyperglycemia degrades image quality in F-18 FDG PET CT by altering bio-distribution of FDG in the body and augmenting soft tissue and muscular uptake. We intend to evaluate the use of short acting I.V insulin in minimising the rescheduling of patients detected with FBG>160 mg/dL on the day of scan. To show the utility of short acting IV insulin therapy in preparation of cancer patients incidentally detected with high blood glucose levels for F-18 FDG PET CT scan, (>160mg/dL) and to compare the obtained image quality with patients detected with fasting blood glucose level (FBG) <100mg/dL and <160 mg/dL, using visual and semi quantitative methods. 613 cancer patients referred for PET CT were divided into 3 groups, Group I (n=30): known diabetics (DM) or incidentally diagnosed with FBG >160 mg/dL, Group II (n=349): DM patients with FBG <160 mg/dL (100-160mg/dL), Group III (n=234): Non DM patients FBG <100mg/dL. In Group I short acting insulin was given intravenously using a sliding scale, post insulin after 90 minutes F-18 FDG (radiotracer) injection was given and PETCT scan was obtained 60 mins post radiotracer injection. Qualitative image analysis was done using biodistribution score and quantitative analysis was done by chi square test, ANOVA (analysis of variance) and paired t-test. In group I patients post insulin there was significant decrease in FBG levels (216±22.2 to 136±13.4mg/dL) and acceptable image quality. Comparison of quantitative parameters (mean and maximum SUV calculated by drawing ROI around brain, heart, liver, muscle, subcutaneous fat) among the 3 groups showed significant intergroup difference with p value <0.05. This short acting I.V insulin protocol is safe and can be used to obtain optimal quality F-18 FDG PET CT scan images by alleviating the need for rescheduling patients though they present with high glucose levels.


New Functions and Subcellular Localization Patterns of c-di-GMP Components (GGDEF Domain Proteins) in B. subtilis.
The universal and pleiotropic cyclic dinucleotide second messenger c-di-GMP is most prominently known to inversely regulate planktonic and sessile lifestyles of Gram-negative species. In the Gram-positive model organism Bacillus subtilis, intracellular c-di-GMP levels are modulated by a concise set of three diguanylate cylases (DgcK, DgcP, DgcW) and one phosphodiesterase (PdeH). Two recent studies have reported the negative influence of the c-di-GMP receptor DgrA (PilZ domain protein) on swarming motility indicating a conserved role of this second messenger across the bacterial domain. However, it has been suggested that the degenerated GGDEF protein YdaK and the inactive EAL domain protein YkuI may also function as c-di-GMP receptors regulating potentially other processes than motility. Here we describe a novel c-di-GMP dependent signaling network in B. subtilis regulating the production of an unknown exopolysaccharide (EPS) that leads to strongly altered colony morphologies upon overproduction. The network consists of the c-di-GMP receptor YdaK and the c-di-GMP synthetase DgcK. Both proteins establish a spatially close signal-effector cluster at the membrane. The cytoplasmic DgcP synthetase can complement for DgcK only upon overproduction, while the third c-di-GMP synthetase, DgcW, of B. subtilis is not part of the signaling pathway. Removal of the regulatory EAL domain from DgcW reveals a distinct function in biofilm formation. Therefore, our study is compatible with the "local pool signaling" hypothesis, but shows that in case of the yda operon, this can easily be overcome by overproduction of non-cognate DGCs, indicating that global pools can also confer signals to regulatory circuits in a Gram-positive bacterium.


Neurophysiological measurements in patients with genuine stress incontinence of urine and the relation of neurogenic defects to the presence of spina bifida occulta.
Neurophysiological measurements comprising surface electromyography (EMG) of the urethral and anal sphincters, measurement of the sensory thresholds of the dorsal nerve (DN) of the clitoris and the urethra and sacral reflex latencies from the dorsal nerve to urethra and anus and from the urethra to anus were performed in 44 females with genuine stress incontinence, in order to detect any relationship between the clinical disorder and a neurogenic defect in the innervation of the muscles involved in maintaining continence. Plain X-rays of the renal tracts (KUB films) were also studied to establish whether the prevalence of spina bifida occulta was increased in this group of patients and was a likely explanation for the nerve defects. Forty-three patients were found to have abnormal neurophysiological responses and the prevalence of spina bifida occulta was 50%, which compares with a prevalence of 17% in normal female controls. Genuine stress incontinence appears to be at least partly associated with defective innervation of the lower urinary tract and it is likely that in some cases the defect may be related to the presence of spina bifida occulta.


Immunologic and viral factors in Sjögren's syndrome.
Sjögren's syndrome is a multifactorial disease in which genetic and possibly viral factors play major roles. The recent development of an SS-like disease in patients infected with HIV-1 suggests a possible retrovirus.


The establishment of a nurse consultant role in paediatric intensive care: a reflective analysis.
Through a review of literature and research, together with reflection on clinical practice, this article reflectively analyses and evaluates the concept of the establishment and development of a nurse consultant post in paediatric intensive care. Manley's (1997) conceptual framework is used as a structure for the reflection, which has enabled a detailed and logical approach and allowed both reflection and analysis of the role in relation to the speciality. It is evident that nurse consultant posts have been developed in a variety of clinical specialities and are providing a real opportunity to improve patient care, progress nursing as a profession and provide a clinical career framework for nurses. The concept of the nurse consultant in paediatric intensive care is both innovative and strategic: Manley has identified many sub-roles, skills and processes necessary to influence and develop the role. The elements of 'transformational leadership', 'change agent' and 'collaborator' identified by Manley appear to hold the key to the ability to influence and develop paediatric intensive care nursing from a practice perspective.


Utilizing the ultraviolet (UV detect) camera to enhance the appearance of photodamage and other skin conditions.
Ultraviolet (UV) light (Wood's light) has been used since 1903 to document alterations in the pigment of the skin. The development of standard UV photographic methods has allowed better opportunities for patient education and the monitoring of their therapeutic progress. To incorporate standardized UV photography into our cosmetic dermatology practice as a tool for patient teaching and monitoring therapeutic programs. Patients with Fitzpatrick Type I to III skin types were photographed with visible and ultraviolet light. The resultant photographic prints were discussed with the patient. When appropriate, therapeutic programs to reverse the findings were instituted for these patients. Follow-up photographs were used to document changes. The UV camera became a useful tool in our practice. One picture was worth a thousand words. The UV camera documented pigment changes, melasma, vitiligo, and posttraumatic or postsurgical hypopigmentation. The UV camera was also useful to monitor treatment programs designed to redistribute the pigment. The UV camera should become an integral part of sun damage detection both in the physician's office and in the community. Not only does the camera document pigmentary changes but it also demonstrates improvement after therapeutic intervention.


Elevated urinary 8-isoprostaglandin F(2alpha) in females with Graves' hyperthyroidism.
In this study, we investigate how oxidative stress alters the urinary F2-isoprostanes' level and we examine the correlation between 8-isoPGF(2alpha) and thyroid hormones in female patients with Graves' hyperthyroidism. We quantitatively determined the concentrations of urinary F2-isoprostanes using gas chromatography-mass spectrometry in the selected ion-monitoring mode. We recruited individuals in the following three groups of subjects for this study: (1) female hyperthyroidism patients (n = 14, 21-71 years), (2) female hypothyroidism patients (n = 16, 16-66 years), and (3) female age-matched normal controls (n = 10, 20-61 years). The average concentration of 8-iso prostaglandin F(2alpha) (8-isoPGF(2alpha)) in hyperthyroidism patients was significantly higher than that in the healthy controls (P < 0.05). The concentration of 8-isoPGF(2alpha) in hypothyroidism patients was similar to that in normal controls. Although the level of 8-isoPGF(2alpha) in two of the patients was slightly elevated, the P value was not significant (NS). Our data suggest that the increased level of urinary 8-isoPGF(2alpha) may reflect possible oxidation injuries in hyperthyroidism patients due to the high level of thyroid hormones. Therefore, the elevated 8-isoPGF(2alpha) in patients could be used as an important biomarker for hyperthyroidism disease.


Cardiovascular function is not associated with creatine kinase activity in a black African population: The SABPA study.
Higher creatine kinase (CK) activity is associated with the development of cardiovascular disease in black African populations. We compared CK activity and investigated associations of blood pressure with CK activity in black and white men as well as black and white women. Ambulatory blood pressure, total peripheral resistance and pulse wave velocity of 197 black and 208 white participants were determined and serum CK activity was measured. Blood pressure and pulse wave velocity were higher in black men and women (all p < 0.001) when compared to their white counterparts. CK activity only varied between black and white women (75.9 U/l vs 62.8 U/l, p = 0.009), even after adjusting for age, body mass index and physical activity. Despite the worse cardiovascular profile of black men and women, and the higher CK activity in the black women, we were unable to link blood pressure, pulse wave velocity or total peripheral resistance with CK activity, in the black African population. In white men, total peripheral resistance was associated with CK activity (R (2) = 0.32; β = 0.25; p = 0.009), whereas systolic blood pressure (R (2) = 0.46; β = 0.17; p = 0.03) and pulse pressure (R (2) = 0.31; β = 0.21; p = 0.01) were associated with CK activity in white women. The lack of associations in the black African population suggests that the link between a worse cardiovascular profile and CK activity may be overshadowed by other contributing factors. Whereas, the established link between cardiovascular function and CK activity in the white groups may be the result of enhanced smooth muscle cell contractility and/or attenuated nitric oxide synthesis capacity.


Resistance to targeted cancer drugs through hepatocyte growth factor signaling.
Cancer therapeutics that target a signaling pathway to which the cancer cells are addicted can deliver dramatic initial responses, but resistance is nearly always inevitable. A variety of mechanisms that cancer cells employ to escape from targeted cancer drugs have been described. We review here the role of Hepatocyte Growth Factor (HGF) and its receptor MET in drug resistance. We present data demonstrating that HGF can confer resistance to a number of kinase inhibitors in a variety of cancer cell lines and discuss our results in relation to the findings of others. Together, these data point at a major role for HGF/MET signaling in resistance to a variety of targeted cancer drugs.


Prenatal ultrasound diagnosis of neural tube defects. Pictorial essay.
Neural tube defects (NTD) are a heterogeneous group of malformations resulting from failure of normal neural tube closure before the fourth and fifth week of embryologic development. The three most common forms of NTD are: anencephaly, encephalocele and spinal dysraphism. Less common forms of neural tube defects include iniencephaly, amniotic bands and other types of spinal abnormalities including scoliosis/cyphosis, sacral agenesis, limb-body wall complex, diastematomyelia. The most part of these abnormalities are accessible to the ultrasound diagnosis in the midtrimester and sometimes even in the late first trimester of the pregnancy. This kind of abnormalities can occur in isolation or in association with other anomalies, which can also be characterized with ultrasound. In this pictorial essay the ultrasonographic aspects of the NTD will be discussed.


Amyloid-like fibril elongation follows michaelis-menten kinetics.
A number of proteins can aggregate into amyloid-like fibrils. It was noted that fibril elongation has similarities to an enzymatic reaction, where monomers or oligomers would play a role of substrate and nuclei/fibrils would play a role of enzyme. The question is how similar these processes really are. We obtained experimental data on insulin amyloid-like fibril elongation at the conditions where other processes which may impact kinetics of fibril formation are minor and fitted it using Michaelis-Menten equation. The correlation of the fit is very good and repeatable. It speaks in favour of enzyme-like model of fibril elongation. In addition, obtained [Formula: see text] and [Formula: see text] values at different conditions may help in better understanding influence of environmental factors on the process of fibril elongation.