Longitudinal Association Between Depression and Inflammatory Markers: Results From the Netherlands Study of Depression and Anxiety.
While cross-sectional associations of inflammatory markers interleukin-6 (IL-6) and C-reactive protein with major depressive disorder are well established, evidence for longitudinal associations mostly comes from studies on depression symptoms, not diagnoses. This study examined cross-sectional and bidirectional longitudinal associations between depression diagnosis and symptoms in an adult sample over a 6-year period. Data were obtained from the baseline (n = 2416) and 2- and 6-year follow-up assessments (n = 1925 and n = 1924, respectively) of the Netherlands Study of Depression and Anxiety. C-reactive protein and IL-6 were assessed at each wave, as were the Composite International Diagnostic Interview and Inventory of Depressive Symptomatology. Linear mixed models and generalized estimating equation models with a binomial distribution were used to study longitudinal associations between depression and inflammation and vice versa. There was a consistent cross-sectional association between current depressive disorder (vs. no current disorder) and symptoms with IL-6 across all follow-up measurements (Cohen's ddepression diagnosis = 0.06, p = .017; Bstandardized Inventory of Depressive Symptomatology = 0.029, SE = 0.011, p = .008). In longitudinal analyses, higher IL-6 levels predicted subsequent chronic course in those with a diagnosis at baseline in women but not in men (odds ratiowomen = 1.13, 95% confidence interval = 1.04-1.23), and both depressive disorder and high severity predicted higher IL-6 levels at the subsequent follow-up (p values < .01). In contrast, C-reactive protein was not associated with current depression in cross-sectional and longitudinal analyses. In this longitudinal study, cross-sectional and bidirectional longitudinal associations were found between depression and IL-6 levels. This underlines the importance of targeting inflammation pathways in the treatment of major depressive disorder. IL-6 could be a potential marker for patient profiling in personalized medicine approaches.


[Evaluation of the usefulness of the physico-chemical study of ascitic fluid in patients with chronic hepatopathies, neoplasms and spontaneous peritonitis].
In order to separate malignancy from chronic liver disease, the ascitic fluid (AF) of 45 in-patients was studied prospectively. Protein, cholesterol, triglycerides, LDH and glucose concentrations were determined in AF. Ascites/Serum (A/S) protein and LDH ratios were also established. Spontaneous bacterial peritonitis (SBP) incidence was studied in the cirrhotic group performing the pH, PMN count and culture of the AF. The 45 patients were classified in three groups: 29 with chronic liver disease, 10 with malignancy and 6 with miscellaneous pathology. Af protein concentration, its A/S ratio and AF cholesterol concentration were statistically significant (p less than 0.001) to differentiate malignancy from chronic liver disease. However, the AF glucose, triglycerides and LDH concentrations and the A/S LSH ratio were not useful in the differential diagnosis. The SBP incidence was 13%, its mortality rate 75% and the cultures were positive only in 25%.


Impaired triacylglycerol catabolism in hypertriglyceridemia of the diabetic, cholesterol-fed rabbit: a possible mechanism for protection from atherosclerosis.
The etiology of the hypertriglyceridemia in alloxan-diabetic rabbits was studied by two independent methods. Production and removal rates of VLDL triacylglycerol were measured in diabetic rabbits by injection of [3H]palmitate-labelled VLDL. Similarly, triacylglycerol total removal rates were determined in non-diabetic rabbits which were infused with Intralipid to mimic the plasma triacylglycerol concentrations of diabetic rabbits. Compared to nondiabetic rabbits, triacylglycerol removal rats were decreased in diabetic rabbits, particularly at higher levels of plasma triacylglycerol. During cholesterol and triacylglycerol supplementation of the diet, post-heparin plasma lipoprotein lipase activity of diabetic rabbits with severe hypertriglyceridemia averaged 36% of that of nondiabetics, suggesting an impaired triacylglycerol removal capacity. Furthermore, plasma triacylglycerol was inversely related to post-heparin plasma lipoprotein lipase activity among diabetic rabbits. VLDL triacylglycerol production increased with increasing plasma triacylglycerol concentration among diabetic cholesterol-fed rabbits with moderately severe hypertriglyceridemia, but reached an apparent plateau among rabbits with plasma triacylglycerol concentrations from approx. 2000-9000 mg/dl. Thus, severe hypertriglyceridemia in this model of insulin deficiency can be attributed only partially to VLDL hypersecretion, whereas a removal defect, resulting in saturation of the triacylglycerol removal mechanism, appears to be largely responsible. The impaired removal of plasma triacylglycerol is also related to the presence of cholesterol predominantly in lipoproteins of increased size. The data support the hypothesis that protection against atherosclerosis in cholesterol-fed diabetic rabbits results from exclusion of very large cholesterol-containing lipoproteins from the arterial wall.


Efficacy of a laser with a pulse duration of 300 ps in skin rejuvenation and treatment of pigmentation disorders in Asians: a series of four cases.
The photothermal effect of lasers is minimized and the photoacoustic effect is maximized as the pulse duration is shortened. Therefore, picosecond lasers with a short pulse and high peak power can be used to effectively treat various pigment disorders by reducing tissue damage. The first picosecond lasers were used for tattoo removal; they are also widely used for pigment treatment because of their reduced side effects compared with nanosecond lasers. Recently, picosecond lasers have been shown to be effective in the treatment of various skin conditions such as acne scars and large pores. There are many studies on picosecond lasers; however, there are no studies on a laser with a pulse duration of 300 ps. This report describes the use of a 300 ps Nd:YAG laser for treating pigment disorders and for skin rejuvenation in four Asians, with no side effects. Determining the clinical significance of the 300 ps pulse duration through comparative studies with various picosecond lasers is needed.


Analysis of Huntingtin-associated protein 1 in mouse brain and immortalized striatal neurons.
Huntingtin, the protein product of the Huntington's disease (HD) gene, is expressed with an expanded polyglutamine domain in the brain and in nonneuronal tissues in patients with HD. Huntingtin-associated protein 1 (HAP-1), a brain-enriched protein, interacts preferentially with mutant huntingtin and thus may be important in HD pathogenesis. The function of HAP-1 is unknown, but recent evidence supports a role in microtubule-dependent organelle transport. We examined the subcellular localization of HAP-1 with an antibody made against the NH2-terminus of the protein. In immunoblot assays of mouse brain and immortalized striatal neurons, HAP-1 subtypes A and B migrated together at about 68 kD and separately at 95 kD and 110 kD, respectively. In dividing clonal striatal cells, HAP-1 localized to the mitotic spindle apparatus, especially at spindle poles and on vesicles and microtubules of the spindle body. Postmitotic striatal neurons had punctate HAP-1 labeling throughout the cytoplasm. Western blot analysis of protein extracts obtained after subcellular fractionation and differential centrifugation of the clonal striatal cells showed that HAP-1B was preferentially enriched in membrane fractions. Electron microscopic study of adult mouse basal forebrain and striatum showed HAP-1 localized to membrane-bound organelles including large endosomes, tubulovesicular structures, and budding vesicles in neurons. HAP-1 was also strongly associated with an unusual large "dense" organelle. Microtubules were labeled in dendrites and axonal fibers. Results support a role for HAP-1 in vesicle trafficking and organelle movement in mitotic cells and differentiated neurons and implicate HAP-1B as the predominant molecular subtype associated with vesicle membranes in striatal neurons.


RAE1ε ligand expressed on pancreatic islets recruits NKG2D receptor-expressing cytotoxic T cells independent of T cell receptor recognition.
The mechanisms by which cytotoxic T lymphocytes (CTLs) enter and are retained in nonlymphoid tissue are not well characterized. With a transgenic mouse expressing the NKG2D ligand retinoic acid early transcript 1ε (RAE1ε) in β-islet cells of the pancreas, we found that RAE1 expression was sufficient to induce the recruitment of adoptively transferred CTLs to islets. This was dependent on NKG2D expression by the CTLs and independent of antigen recognition. Surprisingly, the recruitment of CTLs resulted in the subsequent recruitment of a large number of endogenous lymphocytes. Whereas transgenic mice did not develop diabetes, RAE1 expression was sufficient to induce insulitis in older, unmanipulated transgenic mice that was enhanced by viral infection and pancreatic inflammation. These results demonstrate that the expression of an NKG2D ligand in islets is sufficient to recruit CTLs regardless of their antigen specificity and to induce insulitis.


MicroRNAs as an emerging target for melanoma therapy.
Despite the growing focus on microRNAs (miRNAs) as novel diagnostic tools and therapeutic targets in cancer, global characterization of miRNA expression patterns and their specific targets in melanoma has lagged. In this issue, Reuland et al. (2012) identify miR-26a as being specifically downregulated in human melanoma cells. They further establish Silencer of Death Domains as a novel target for miR-26a, which functionally mediates melanoma cell death. These findings suggest that miR-26a may serve as a promising novel therapy for subsets of melanoma.


Co-expression of nerve growth factor and p75NGFR in the inferior alveolar nerve after mandibular distraction osteogenesis.
During mandibular distraction osteogenesis (DO), the inferior alveolar nerve (IAN) is damaged during distractor activation, but spontaneously recovers during consolidation. Although many neurotrophic factors are known to play critical roles, there have been few studies on the mechanism of peripheral nerve recovery after DO. The aim of this study was to observe the expression pattern of p75NGFR (low-affinity receptor of NGF) and to detect autocrine growth activity in IANs following mandibular DO. Unilateral mandibular distractions (0.5mm each, twice per day for 10 days) were conducted on eight mongrel dogs. Two each were killed at 7, 14, 28 and 56 days after completing distraction. The distracted IAN and contralateral control nerve were harvested. Immunohistochemical staining was performed to determine p75NGFR expression, and double immunofluorescent staining to detect NGF and p75NGFR co-expression. Levels of p75NGFR expression were found to be significantly elevated at 7 and 14 days in Schwann cells located in the outer layer of axon, but were almost undetectable at 28 and 56 days. In double immunofluorescent images, the co-expression of NGF and p75NGFR was also detected at 7 and 14 days. p75NGFR plays an important role in remyelination due to its abundant expression in Schwann cells of damaged nerves, and NGF is an autocrine growth factor present in distracted IANs during the early consolidation period after mandibular DO.


Stem cell therapy for electrophysiological disorders.
Cardiovascular diseases are a leading cause of mortality worldwide. Terminally differentiated adult cardiomyocytes lack the innate ability to regenerate. Cell- and gene-based therapies are emerging as exciting new experimental strategies for myocardial repair and treatment of a variety of cardiovascular diseases. The potential advantages and shortcomings of each strategy for electrophysiological disorders are discussed. Since the first description of human induced pluripotent stem cell-derived cardiomyocytes, these cells have garnered tremendous interest for their potential use in patient-specific analysis and therapy. However, a full understanding of their electrophysiological and contractile function is necessary before this potential can be realized. This review focuses on the mechanisms by which stem cell therapy may function as an antiarrhythmic treatment and early clinical results.


The use of a portable refractometer to measure desflurane.
The measurement of volatile anaesthetic agents by infrared absorption is liable to interference by other gases which absorb infrared light. In particular, nitrous oxide may, in principle, interfere with the measurement of desflurane. On the other hand, the refractometer should be immune to such effects. We demonstrated that interactions may occur between desflurane and nitrous oxide with some gas analysers and that the refractometer remains a useful instrument.


The evaluation of microscopic hematuria: a population-based study.
From 1979 until 1983, 2,005 men underwent routine urological examinations. Of these men 85 (4 per cent) had asymptomatic microscopic hematuria. All men underwent complete urological evaluation. Significant urological disease was detected in 22 per cent of the patients. Therefore, complete urological evaluation can be justified in a nonselected group of men with microscopic hematuria.


Paracrocinitomix mangrovi gen. nov., sp. nov., isolated from a mangrove sediment: proposal of two new families, Phaeocystidibacteraceae fam. nov. and Owenweeksiaceae fam. nov., and emended description of the family Schleiferiaceae.
A Gram-stain-negative and short rod-shaped bacterial strain designated GM2-3-6-6T was obtained from a mangrove sediment. Cells were light yellow-pigmented, catalase-positive and oxidase-positive. Carotenoid pigment was produced. Phylogeny of the 16S rRNA gene showed that strain GM2-3-6-6T was affiliated to the family Crocinitomicaceae, sharing maximum sequence similarities with Crocinitomix algicola 0182T, C. catalasitica IFO 15977T, and Putridiphycobacter roseus SM1701T of 93.8%, 93.6%, and 92.5%, respectively. The average nucleotide identity values, digital DNA-DNA hybridization estimates and average amino acid identity values between strain GM2-3-6-6T and the three close relatives were 68.6-68.8%, 18.5-19.2%, and 59.0-62.3%, respectively. The complete circular genome of strain GM2-3-6-6T was 4,365,762 bp in length with a DNA G + C content of 35.0%. The respiratory quinone was MK-7. The major polar lipids consisted of phosphatidylethanolamine, two unidentified phospholipids, one unidentified aminoglycolipid, one unidentified aminolipid and four other unidentified lipids. The major fatty acids were iso-C15:0, iso-C15:1 G, summed feature 3 (C16:1ω7c and/or C16:1ω6c), and iso-C17:0 3-OH. Based on genomic, phenotypic, and chemotaxonomic characterizations, strain GM2-3-6-6T represents a novel species of a novel genus, for which the name Paracrocinitomix mangrovi gen. nov., sp. nov. is proposed. The type strain is GM2-3-6-6T (= MCCC 1K04831T = KCTC 82931T). Additionally, phylogenomic analysis of the type strains of the family Schleiferiaceae and family Cryomorphaceae related members including uncultivated bacteria, was performed using the Genome Taxonomic Database toolkit (GTDB-Tk). Based on 16S rRNA gene phylogeny and genomic features, two novel families, Phaeocystidibacteraceae fam. nov. and Owenweeksiaceae fam. nov. are proposed. An emended description of the family Schleiferiaceae is also proposed.


Clinically significant endoscopic findings in a dyspeptic rural population cohort of Sindh, Pakistan: Are we over-investigating?
To discuss the clinically significant endoscopic findings of the upper GI tract and their association with different age groups in a dyspeptic rural population of Gadap town, Sindh. This was a retrospective secondary data analysis of 806 patients conducted in the medical ward of Fatima Hospital, Baqai Medical University from December 2016 to May 2019. It was approved by the University Ethics Committee. Patients' demographics and other data related to the procedure were recovered from patients' records. SPSS version 20 was used for statistical analysis. There were marginally more women suffering from dyspepsia as opposed to men (51.5% vs 48.5% respectively). Majority of the patients were less than 45 years of age, with most procedures being performed as outpatients. Nearly 40% of the patients did not have clinically relevant endoscopic findings. Most common significant finding on endoscopic examination was gastritis followed by hiatal hernia. Normal upper gastrointestinal endoscopy, regardless of age, is a common finding in patients suffering from dyspepsia in our setting. Therefore, in a resource constraint environment like ours, expensive endoscopic procedures should be reserved for those patients who are not responding to medical therapy or those who have alarm symptoms.


Prognosis of occlusive disease of the circle of Willis (moyamoya disease) in children.
The prognosis of 27 patients with moyamoya disease was studied. The ages at onset ranged from 11 months to 4-11/12 years. Follow-up study was performed within 4 years from the onset in 13, 5 to 9 years in 5, and 10 to 15 years in 9. Transient ischemic attacks (TIA) occurred most often during the first four years and decreased thereafter. Intellectual deterioration and neurologic deficits increased with time. Outcome included no sequelae in five (19%), occasional TIA or headache alone in nine (33%), mild intellectual and/or motor impairment in seven (26%), requirement for special school or care by parents or institutions after reaching the teen years in three (11%), continuous 24-hour care in two (7%), and death in one (3%). Poor prognosis was correlated with an early age at onset and hypertension.


Developmental regression and movement disorder as a phenotypic variant of POLR3A Mutation-Case report.
POLR3A is a main subunit encoding RNA polymerase III, which is involved in transcription of many RNA structures. Here, we report a new presentation of c.1771-6C > G intronic variant presenting as developmental regression, seizure, and dystonia in a 6-year-old boy associated with striatum involvement in the brain MRI.


Archeological Tourist Destination Image Formation: Influence of Information Sources on the Cognitive, Affective and Unique Image.
A destination's image is a critical factor in tourists' perceptions and evaluations of said destination. This paper analyzes the formation of the tourist destination image of Segóbriga Archeological Park, a cultural destination located in the province of Cuenca (Spain) that holds great heritage value. To this end, the paper adopted a multidimensional approach and used PLS-SEM to analyze the destination image, taking into account not only its cognitive and affective components, but also the unique image component. The latter has received less attention in the literature and is a novel factor among cultural destinations. The results show that this component is essential to the overall image of an archeological destination, but is not influenced by information sources.


Shifts in sediment bacterial communities reflect changes in depositional environments in a fluviatile context.
Sediments are complex heterogeneous matrices allowing to some extent the recording of past environmental conditions by integrating sediment characteristics, contamination and the microbial community assembly. In aquatic environments, abiotic environmental filtering is considered the primary deterministic mechanism shaping microbial communities in sediments. However, the number and relative contributions of geochemical and physical factors associated with biotic parameters (reservoir of microorganisms) complicate our understanding of community assembly dynamics. In this study, the sampling of a sedimentary archive in a site alternately subjected to contrasting inputs from the Eure and the Seine Rivers allowed us to study the response of microbial communities to changes in depositional environment over time. The coupling of the quantification and sequencing of the gene encoding the 16S rRNA with analyses of grain size, organic matter and major and trace metal contents demonstrated that microbial communities reflected contrasting sedimentary inputs over time. Total organic carbon (TOC) was the main factor influencing microbial biomass, while the quantity and quality of organic matter (R400, RC/TOC), major elements (i.e. Al, Fe, Ti) and trace metals (i.e. Zn, Pb, Cu, Cr, Ni, As, Co, Ag, Sb) shaped the structure of the microbial community. Besides the effect of geochemical factors, a specific microbial signature was associated with the contrasting sedimentary sources, highlighting the importance of the microbial reservoir in the assembly of microbial communities. Indeed, the main genera identified in the facies influenced by the Eure River were affiliated with the phyla Desulfobacterota (Syntrophus, Syntrophorhabdus, Smithella, Desulfatiglans), Firmicutes (Clostridium_sensu_stricto_1), Proteobacteria (Crenothrix), Verrucomicrobiota (Luteolibacter), while the contributions of the Seine River were characterised by some halophilic genera Salirhabdus (Firmicutes), Haliangium (Myxococcota) and SCGC-AB-539-J10 (Chloroflexi). This study sheds light on the overall processes determining the assembly of microbial communities in sediments and the importance of associating geochemical factors with reservoirs of microorganisms inherited from sediment sources.


Kynurenate and 7-chlorokynurenate formation in chronically epileptic rats.
The tryptophan metabolite kynurenic acid (KYNA) and its synthetic derivative, 7-chlorokynurenic acid (7-Cl-KYNA), are antagonists of the glycine co-agonist ("glycine(B)") site of the N-methyl-D-aspartate (NMDA)-receptor. Both compounds have neuroprotective and anticonvulsive properties but do not readily penetrate the blood-brain barrier. However, KYNA and 7-Cl-KYNA can be formed in, and released from, astrocytes after the peripheral administration of their transportable precursors kynurenine and 4-chlorokynurenine, respectively. The present study was designed to examine these biosynthetic processes, as well as astrogliosis, in animals with spontaneously recurring seizures. The fate and formation of KYNA and 7-Cl-KYNA was studied in vivo (microdialysis) and in vitro (tissue slices) in rats exhibiting chronic seizure activity (pilocarpine model) and in appropriate controls. Neuronal loss and gliosis in these animals were examined immunohistochemically. In vivo microdialysis revealed higher ambient extracellular KYNA levels and enhanced de novo formation of 7-Cl-KYNA in the entorhinal cortex and hippocampus in epileptic rats. Complementary studies in tissue slices showed increased neosynthesis of KYNA and 7-Cl-KYNA in the same two brain areas. Microscopic analysis revealed pronounced astrocytic reactions in entorhinal cortex and hippocampus in epileptic animals. These results demonstrate that the epileptic brain can synthesize glycine(B) receptor antagonists in situ. Astrogliosis probably accounts for their enhanced production in chronically epileptic rats. These results bode well for the use of 4-chlorokynurenine in the treatment of chronic seizure disorders.


Distinct roles for B7 costimulation in contact hypersensitivity and humoral immune responses to epicutaneous antigen.
Productive interactions between B7-1 and B7-2 costimulatory molecules on dendritic cells (DC) and CD28 on T cells are thought to be critical for successful antigen presentation. Epicutaneous application of haptens induces both contact hypersensitivity (CHS), an inflammatory cutaneous response mediated by CD8+ T cells, and an anti-hapten antibody response mediated by CD4+ helper T cells. The role of B7 costimulation in the immune response to oxazolone (Ox) was analyzed using mice lacking either B7-1 (B7-1-/-), B7-2 (B7-2-/-), or both (Db-/-) of these costimulatory molecules. The absence of both B7-1 and B7-2 results in diminished CHS. This inhibition is largely overcome at higher hapten sensitizing doses indicating the presence of compensatory pathways. In contrast, anti-Ox IgG1 and IgG2a responses were not detected in the absence of both B7-1 and B7-2, even at high sensitizing doses, indicating an obligatory role of B7 costimulation in IgG class switching. B7-1 and B7-2 have overlapping functions in both CHS responses and anti-hapten response. B7-2-/- mice demonstrated a modestly reduced CHS response only at very low doses of Ox (0.05%), but responded normally at higher Ox doses, and B7-1-/- mice had CHS responses indistinguishable from those of wild-type mice. Similarly, anti-Ox IgG responses were comparable in wild-type, B7-1-/- and B7-2-/- mice. Taken together, these studies reveal distinct roles for B7 costimulation in response to epicutaneous antigens with an obligatory role for IgG class switching and an important, but nonessential role for CHS responses.


The Pipkin fracture-dislocation of the hip.
The 'Pipkin' fracture-dislocation of the hip is an injury that is easily missed and is associated with serious sequelae. Eighty posterior dislocations of the hip were studied; there were nine 'Pipkin' injuries, seven of which are reported. The aetiology and management is discussed and the literature is reviewed. Guidelines for management are suggested.


Urologic Emergencies.
The diagnosis and management of urologic emergencies are incorporated into the basic training of all urology residents. In institutions without access to urologic services, it is usually left to the General Surgeon or Emergency Medicine physician to provide timely care. This article discusses diagnoses that are important to recognize and treatment that is practically meaningful for the non-Urologist to identify and treat. The non-Urology provider, after reading this article, will have a better understanding and a higher comfort level with treating patients with urologic emergencies.


Global asymptotic stability of the active disassembly model of flagellar length control.
Organelle size control is a fundamental question in biology that demonstrates the fascinating ability of cells to maintain homeostasis within their highly variable environments. Theoretical models describing cellular dynamics have the potential to help elucidate the principles underlying size control. Here, we perform a detailed study of the active disassembly model proposed in Fai et al. (elife 8:e42599, 2019). We construct a hybrid system which is shown to be well-behaved throughout the domain. We rule out the possibility of oscillations arising in the model and prove global asymptotic stability in the case of two flagella by the construction of a suitable Lyapunov function. Finally, we generalize the model to the case of arbitrary flagellar number in order to study olfactory sensory neurons, which have up to twenty cilia per cell. We show that our theoretical results may be extended to this case and explore the implications of this universal mechanism of size control.


Interstitial deletion of the long arm of chromosome 2 in a polymalformed newborn--karyotype: 46,XX,del(2)(q21;q24).
This report describes a polymalformed female newborn presenting an interstitial deletion of the long arms of chromosome 2. Karyotype: 46,XX,del(2)(q21 q24).


Interpreting the results of explicit and applied theory of mind collectively in autistic children: A solution from Rasch analysis.
Theory of mind is an ability to infer others' mental states, which is a foundation for generating appropriate social responses. Theory of mind can be conceptually divided into two related but distinguishable constructs: explicit theory of mind (conceptual knowledge/information about others' mental states) and applied theory of mind (the ability to use theory of mind skills in real-life contexts). Although these two theory of mind scores can be described by the percentages of children in the early, basic, and advanced developmental stages, the resulting information may not be sufficient to determine the corresponding relationships between these two theory of mind constructs or identify children with mismatched theory of mind abilities (e.g. children who have difficulty in effectively applying their theory of mind knowledge in real-life contexts). To resolve these limitations, methods for simultaneously interpreting the relationships between the two theory of mind scores are proposed. Based on the findings, each applied theory of mind score can reflect multiple scores of explicit theory of mind. In particular, the results do not take measurement error into consideration, which would make them more ambiguous. Therefore, the scores of applied theory of mind should be interpreted carefully, given that children who have the same applied theory of mind score may actually have high or low explicit theory of mind. Regarding the method for joint interpretation, cutoff scores were selected to identify children who have mismatched theory of mind abilities (high explicit theory of mind with low applied theory of mind or low explicit theory of mind with high applied theory of mind) and determine the priority for interventions.


Amelioration of intestinal reperfusion injury by moderate hypothermia is associated with serum sICAM-1 levels.
The aim of this study was to investigate the effects of moderate hypothermia on various serum markers involving in inflammation after intestinal ischemia-reperfusion (IR). The model of 30 min intestinal ischemia +90 min reperfusion was used. Three groups of rats were studied, n=7-8 per group: 1) sham at normothermia, 36.5 to 37.5 degrees C; 2) IR at normothermia and; 3) IR at moderate hypothermia, 32 to 33 degrees C. Serum levels of TNF-alpha, lipopolysaccharide-inducible CXC chemokine (LIX), and soluble intercellular adhesion molecule-1 (sICAM-1) were determined using ELISA technique. Histological features of terminal ileum were also graded. Intestinal IR at normothermia caused remarkable tissue injury together with an elevation in serum TNF-alpha, LIX, and sICAM-1 levels. Moderate hypothermia significantly decreased the degree of mucosal damage and attenuated the elevation of serum sICAM-1 levels. However, there were no significant differences in serum TNF-alpha and LIX levels between IR at normothermia and IR at hypothermia. Intestinal IR at normothermia induces the elevation of serum TNF-alpha, LIX, and sICAM-1 levels. Moderate hypothermia protects the small intestine from reperfusion injury. This beneficial effect is associated with serum sICAM-1 levels but not with serum TNF-alpha and LIX levels. We speculate that one of the mechanisms, by which hypothermia blunts the tissue injury, is at the step of firm adhesion between leukocytes and endothelial cells.


Functionalization of Magnetic Beads with Biotinylated Nanobodies for MALDI-TOF/MS-Based Quantitation of Small Analytes.
Over the last two decades, the variable domains from heavy chain-only antibodies in camelids (nanobodies) have emerged as valuable immunoreagents for analytical and diagnostic applications. One prominent use of nanobodies is for the detection of small molecules due to their ease of production, resistance to solvents used in sample extraction, facile genetic manipulation, and small size. These last two properties make it possible to produce biotinylated nanobodies in vivo, which can be loaded in an orientated manner on magnetic beads covered with avidin, creating high-density immunoadsorbenpi twbch ""ts. The method described here details the use of nanobody-based adsorbents to concentrate small molecular weight analytes for subsequent quantitative analysis by MALDI-TOF mass spectrometry. Quantitation requires the inclusion of an internal standard (IS), a compound with properties similar to those of the analyte, enabling compensation for uneven distribution during crystallization of the MALDI-TOF matrix. Since nanobody generation against small compounds requires conjugation to carrier proteins, the same conjugation chemistry can be used to synthesize the IS. By design the IS cross reacts with the capture nanobody and can be preloaded in the immunoadsorbent, facilitating quantitative detection of the target compound.


Common abdominal emergencies in children.
Because young children often present to EDs with abdominal complaints, emergency physicians must have a high index of suspicion for the common abdominal emergencies that have serious sequelae. At the same time, they must realize that less serious causes of abdominal symptoms (e.g., constipation or gastroenteritis) are also seen. A gentle yet thorough and complete history and physical examination are the most important diagnostic tools for the emergency physician. Repeated examinations and observation are useful tools. Physicians should listen carefully to parents and their children, respect their concerns, and honor their complaints. Ancillary tests are inconsistent in their value in assessing these complaints. Abdominal radiographs can be normal in children with intussusception and even malrotation and early volvulus. Unlike the classic symptoms seen in adults, young children can display only lethargy or poor feeding in cases of appendicitis or can appear happy and playful between paroxysmal bouts of intussusception. The emergency physician therefore, must maintain a high index of suspicion for serious pathology in pediatric patients with abdominal complaints. Eventually, all significant abdominal emergencies reveal their true nature, and if one can be patient with the child and repeat the examinations when the child is quiet, one will be rewarded with the correct diagnosis.


[Use of coated stents in two patients with congenital heart defects and secondary vascular aneurysms].
The formation of an aneurysm in the aorta or pulmonary artery is a dangerous potential complication of surgical and angioplasty procedures involving these vessels. Treatment using covered stents has emerged as an effective alternative to surgery and the use of conventional stents. The authors report on 2 patients who were treated successfully by the implantation of covered stents in the aorta and pulmonary artery following angioplasty and surgery, respectively. We discuss the mechanisms of aneurysm formation and the efficacy and limitations of using covered stents in such patients.


γ-Tubulin interacts with E2F transcription factors to regulate proliferation and endocycling in Arabidopsis.
γ-Tubulin is associated with microtubule nucleation, but evidence is accumulating in eukaryotes that it also functions in nuclear processes and in cell division control independently of its canonical role. We found that in Arabidopsis thaliana, γ-tubulin interacts specifically with E2FA, E2FB, and E2FC transcription factors both in vitro and in vivo. The interaction of γ-tubulin with the E2Fs is not reduced in the presence of their dimerization partners (DPs) and, in agreement, we found that γ-tubulin interaction with E2Fs does not require the dimerization domain. γ-Tubulin associates with the promoters of E2F-regulated cell cycle genes in an E2F-dependent manner, probably in complex with the E2F-DP heterodimer. The up-regulation of E2F target genes PCNA, ORC2, CDKB1;1, and CCS52A under γ-tubulin silencing suggests a repressive function for γ-tubulin at G1/S and G2/M transitions, and the endocycle, which is consistent with an excess of cell division in some cells and enhanced endoreduplication in others in the shoot and young leaves of γ-tubulin RNAi plants. Altogether, our data show ternary interaction of γ-tubulin with the E2F-DP heterodimer and suggest a repressive role for γ-tubulin with E2Fs in controlling mitotic activity and endoreduplication during plant development.


Spatiotemporal data visualisation for homecare monitoring of elderly people.
Elderly people who live alone can be assisted by home monitoring systems that identify risk scenarios such as falls, fatigue symptoms or burglary. Given that these systems have to manage spatiotemporal data, human intervention is required to validate automatic alarms due to the high number of false positives and the need for context interpretation. The goal of this work was to provide tools to support human action, to identify such potential risk scenarios based on spatiotemporal data visualisation. We propose the MTA (multiple temporal axes) model, a visual representation of temporal information of the activity of a single person at different locations. The main goal of this model is to visualize the behaviour of a person in their home, facilitating the identification of health-risk scenarios and repetitive patterns. We evaluate the model's insight capacity compared with other models using a standard evaluation protocol. We also test its practical suitability of the MTA graphical model in a commercial home monitoring system. In particular, we implemented 8VISU, a visualization tool based on MTA. MTA proved to be more than 90% accurate in identify non-risk scenarios, independently of the length of the record visualised. When the spatial complexity was increased (e.g. number of rooms) the model provided good accuracy form up to 5 rooms. Therefore, user preferences and user performance seem to be balanced. Moreover, it also gave high sensitivity levels (over 90%) for 5-8 rooms. Fall is the most recurrent incident for elderly people. The MTA model outperformed the other models considered in identifying fall scenarios (66% of correctness) and was the second best for burglary and fatigue scenarios (36% of correctness). Our experiments also confirm the hypothesis that cyclic models are the most suitable for fatigue scenarios, the Spiral and MTA models obtaining most positive identifications. In home monitoring systems, spatiotemporal visualization is a useful tool for identifying risk and preventing home accidents in elderly people living alone. The MTA model helps the visualisation in different stages of the temporal data analysis process. In particular, its explicit representation of space and movement is useful for identifying potential scenarios of risk, while the spiral structure can be used for the identification of recurrent patterns. The results of the experiments and the experience using the visualization tool 8VISU proof the potential of the MTA graphical model to mine temporal data and to support caregivers using home monitoring infrastructures.


Correlations between immune and metabolic serum markers and schizophrenia/bipolar disorder polygenic risk score in first-episode psychosis.
There is a strong interest in identifying the biological mechanisms involved in the genetic risk for psychotic disorders. In this study, we evaluated the correlation between serum concentrations of specific molecular markers and the genetic component for schizophrenia and bipolar disorder. We analysed the association between the polygenic risk score (PRS) and the serum levels of different inflammatory/metabolic markers in a sample of 81 first-episode psychosis patients (FEP) with a diagnosis of schizophrenia or bipolar disorder and 33 controls. A positive correlation of schizophrenia and bipolar disorder PRS with the inflammatory marker C-C Motif Chemokine Ligand 4 serum concentration (ρ = 0.42, P = 1.56 × 10-04 and ρ = 0.40, P = 1.65 × 10-03 , respectively) and a negative correlation with the serum ghrelin content (ρ = - 0.35, P = 4.27 × 10-03 and ρ = - 0.45, P = 6.05 × 10-04 , respectively) were observed. These findings provide new insight into the biological underpinnings of the PRS component, thus supporting a role of the genetic liability on the inflammatory and metabolic alterations that characterize psychosis onset.


Histone Methyltransferase SETDB1 Regulates the Development of Cortical Htr3a-Positive Interneurons and Mood Behaviors.
GABAergic (gamma-aminobutyric acidergic) interneurons (INs) are highly heterogeneous, and Htr3a labels a subpopulation of cortical INs originating from the embryonic caudal ganglionic eminence. SETDB1 is one of the histone H3K9 methyltransferases and plays an essential role in the excitatory neurons, but its role in regulating cortical inhibitory INs remains largely unknown. In this study, we generated transgenic mice with conditional knockout of Setdb1 in neural progenitor cells (Setdb1-NS-cKO) and GABAergic neurons (Setdb1-Gad2-cKO). In addition, we performed RNA sequencing, ATAC-seq (assay for transposase-accessible chromatin with sequencing), chromatin immunoprecipitation sequencing, luciferase assay, chromatin conformation capture, and CRISPR (clustered regularly interspaced short palindromic repeats)/dCas9 to study the epigenetic mechanism underlying SETDB1-mediated transcriptional regulation of Htr3a. We also performed in situ hybridization and whole-cell recording to evaluate the functional properties of cortical Htr3a+ INs and behavioral tests for mood. We detected significant upregulation of Htr3a expression in the embryonic ganglionic eminence of Setdb1-NS-cKO and identified the endogenous retroviral sequence RMER21B as a new target of SETDB1. RMER21B showed enhancer activity and formed distal chromatin interaction with the promoter of Htr3a. In addition, we observed an increased number and enhanced excitability of Htr3a+ INs in the knockout cortex. Moreover, Setdb1-Gad2-cKO mice exhibited anxiety- and depressive-like behaviors, which were partially reversed by a 5-HT3 receptor antagonist. These findings suggest that SETDB1 represses Htr3a transcription via RMER21B-mediated distal chromatin interaction in the embryonic ganglionic eminence and regulates the development of cortical Htr3a+ INs and mood behaviors.


Use of a Braunula for maxillary sinus irrigation.
Puncture and lavage of the maxillary sinuses is a common procedure in ENT practice. Repeated irrigations are required in chronic sinusitis refractory to treatment. In our department we use a No. 14 gauge Braunula for such cases. Over 100 patients have been treated over the past two years with no significant complications. This device is inexpensive, sterile, safe and easy to use and we recommend its use for patients with chronic maxillary sinusitis requiring repeated irrigations.


SPDEF enhances cancer stem cell-like properties and tumorigenesis through directly promoting GALNT7 transcription in luminal breast cancer.
Luminal breast cancer (BC) is the predominant subtype of breast cancer with a sustained risk of late recurrence and death. Understanding the molecular mechanisms for the oncogenesis of luminal BC would improve the prognosis for this large subset of patients. SPDEF was reported to be dysregulated in breast cancers. However, the biological functions and underlying molecular mechanism of SPDEF in luminal BC remains largely unknown. The aim of the present study was to elucidate the potential roles of SPDEF underlying subtype-specific functions in BC, especially in luminal subtypes. The expressions and clinicopathological characteristics of SPDEF in luminal BC patients were evaluated bioinformatically. In vitro and in vivo assays were performed to investigate the oncogenic function and stemness maintenance of SPDEF in luminal BC. Chromatin immunoprecipitation (ChIP) and dual luciferase reporter assays were conducted to determine the transcription regulation of GALNT7 by SPDEF. GALNT7 levels in serum from luminal BC patients were further detected by enzyme-linked immunosorbent assay (ELISA). SPDEF is markedly upregulated in luminal BC and positively associated with tumor progression and poor prognosis. Furthermore, we confirmed that SPDEF enhanced the proliferation, migration, invasion and stemness of luminal BC cells in vitro as well the tumorigenicity in vivo. Mechanistically, we demonstrated the stimulative effect of SPDEF on the progression and stemness of luminal BC, which is mediated by its directly transcriptional target GALNT7. Clinically, we verified that the GALNT7 can be used as a noninvasive diagnostic marker. Noteworthy, the combined detection of serum GALNT7 and traditional tumor markers can enhance diagnostic accuracy thus is of vital importance in the early diagnosis of luminal BC. Our study reveals a novel mechanism by which SPDEF transcriptionally activates GALNT7 via directly binding to its promoter to promote cell proliferation, motility and stemness, and led to luminal BC tumorigenesis and poor prognosis.


Expression of nuclear receptors and cofactors in human endometrium and myometrium.
To study the expression of nuclear receptors and cofactors in human endometrium and myometrium in proliferative and secretory phases of the menstrual cycle. Multiprobe ribonuclease protection assay and real-time reverse transcriptase polymerase chain reaction were used to quantitate mRNA levels of steroid receptors, vitamin D receptor (VDR), retinoic acid receptors (RAR), and cofactors AIB1 (amplified in breast cancer-1), CBP (cyclic adenosine monophosphate response element binding protein), pCAF (p300/CBP-associated factor), TIF2 (transcription intermediary factor-2), N-CoR (nuclear receptor corepressor), and SMRT (silencing mediator of repressed transcription). Cyclin A expression was analyzed to determine the proliferation status of the tissues. The expression of androgen receptor, estrogen receptors alpha and beta, progesterone receptor, and RARalpha followed cyclin A expression. There was more abundant expression in the proliferative phase endometrium than in the secretory phase endometrium. Glucocorticoid receptor, VDR, RARbeta, and RARgamma were stably expressed during the menstrual cycle in both endometrium and myometrium. Cofactors N-CoR, SMRT, pCAF, CBP, TIF2, AIB1, and p300 mRNAs were expressed in all samples in both endometrium and myometrium. N-CoR, pCAF, AIB1, and p300 appeared not to be regulated when comparing proliferative and secretory phases of the cycle. Individual differences were found in the expression levels of both nuclear receptors and cofactors. The menstrual cycle-dependent regulation of nuclear receptor expression was more apparent in the endometrium than in the myometrium, whereas cofactor expression was not cycle dependent. There were individual differences in the expression levels of different receptors and cofactors. In hormonal therapy these differences might result in different responses, depending on the patient as well as the ligand used.


The meniscus in the cruciate-deficient knee.
Evidence clearly implicates meniscectomy as a primary factor in the premature development of OA of the knee joint. Although data demonstrate the ability of the menisci to transmit load, they do not contribute to the primary stability of the knee. In the absence of the ACL, the menisci have been shown to enhance the knee's stability in the AP, varus-valgus, and internal-external directions in vitro. Clinically, the argument that the menisci are important secondary stabilizers is less clear. The restraining capacity of the menisci to AP translation is much smaller than the forces the knee is subjected to in vivo during activities of daily living. Additionally, these forces can increase as much as threefold during strenuous athletics. It becomes apparent, on review of the literature, that the menisci clearly are not designed to participate as a significant restraining mechanism for the ACL-deficient knee. The incidence of acute meniscal tear is 52% and increases to 83% in the long run. It is important to realize that although the menisci contribute in part to the stability of the ACL-deficient knee, such a role places them at risk for injury. When meniscal lesions are noted in the ACL-deficient knee, it is important to bear in mind the patient's goals, including his or her willingness to have an ACL reconstructive procedure and desire to return to sports. Also, the tear's configuration and location dictate its the ability to heal. One final area of interest relates to the fate of an ACL reconstruction in the meniscus-deficient knee. Although the meniscus is not a participant in primary stability, the subtle alteration in knee joint kinematics may create unfavorable conditions for the ACL graft. It is possible that the menisci may provide some protection to an ACL-reconstructed knee by restoring normal knee joint kinematics. Such a situation may explain why some ACL reconstructions in the meniscectomized knee fail over time. Prosthetic meniscal substitution or allograft meniscal transplantation are techniques on the horizon and may prove useful in the future when the remaining meniscus cannot be repaired.


Recurrent Lower-Extremity Compartment Syndrome after Four-Compartment Fasciotomy Secondary to Acute Limb Ischemia.
Lower-extremity compartment syndrome is a limb-threatening event necessitating emergent treatment using fasciotomy. Recurrent compartment syndrome is rare and has only been reported after trauma and in conjunction with underlying connective tissue disorders. In this report, we present a case of recurrent lower-extremity compartment syndrome caused by ischemia-reperfusion injury, in a patient previously treated with adequate 4-compartment fasciotomies. As such, this is the first reported case of recurrent compartment syndrome in the setting of ischemia-reperfusion injury that required treatment with 4-compartment fasciotomies on both occasions. This case demonstrates that fasciotomy is not protective against the development of recurrent compartment syndrome due to ischemia-reperfusion injury and that patients at high risk require monitoring.


Feasibility of percutaneous nephrolithotomy under assisted local anaesthesia: a prospective study on selected patients with upper urinary tract obstruction.
To evaluate the feasibility of performing percutaneous nephrolithotomy (PCNL) under local anaesthesia in selected patients. Twenty-four patients with unilateral renal obstruction due to pelvic stones > or =2.0 cm were enrolled in our study. First a percutaneous nephrostomy to decompress the obstructed kidney was performed using local anaesthesia (lignocaine). A 16-Fr nephrostomy tube was left in place for 1 wk, and then the second stage was carried out. After having infiltrated the tract and the renal parenchyma with lignocaine, dilatation of the nephrostomy tract was performed. Subsequently, PCNL was done using a 24-Fr rigid nephroscope and a ballistic lithotripter. All patients were premedicated with pethidine HCl intramuscularly 30 min before the beginning of both stages. Diazepam was given (0.1mg/kg orally) to patients before the second stage. Pain scores were collected using 10-cm linear visual analogue scale (VAS) after the completion of both procedures. The procedure was well tolerated. One patient needed further treatment with midazolam during PCNL. The mean VAS score was 38 mm (range: 17-60 mm) for the first stage and 36 mm (13-69 mm) for the second stage. The mean operative time, including both stages, was 127 min (85-155 min). No anaesthesia-related complications occurred. Our study indicates that PCNL under assisted local anaesthesia is safe and effective in selected patients.


Delivery Mode and Neurological Complications in Very Low Birth Weight Infants.
The risk of intraventricular hemorrhage (IVH) and periventricular leukomalacia is associated with low birth weight and gestational age. Caesarean section (CS) may reduce the risk of IVH, although it has been a matter of debate. The aim of this study was to evaluate the influence of the mode of delivery (MOD) on the development of IVH and cystic periventricular leukomalacia (cPVL). We analyzed an initial cohort of 11,023 very low birth weight (VLBW) infants born between January 2010 and December 2019. Infants with major malformations and gestational age <23 weeks and ≥32 weeks were excluded. A final cohort of 8,251 newborns was analyzed. Data was collected from Portuguese National very low birth weight registry. Cases were classified as vaginal delivery (VD) or CS. Outcome was assessed in univariate and logistic regression analyses. The median gestational age was 29 weeks (IQR 3.3) and the median weight was 1,100 g (IQR 555). The prevalence of IVH was significantly higher in the VD group versus the CS group, across all grading levels:1,144 newborns had grade I IVH (16% VD vs. 14% CS, p <0.01), 706 had grade II IVH (12% VD vs. 7.6% CS, p <0.01), and 777 had grade III IVH (14% VD vs. 7.9% CS, p <0.01). Post-hemorrhagic ventricular dilatation occurred in 457 newborns (8.3% VD vs. 4.6% CS, p <0.01) and 456 newborns had periventricular hemorrhagic infarction (8.4% VD vs. 4.5% CS, p <0.01). There was no association between MOD and cPVL. After applying a logistic regression analysis, including known risk factors for IVH and cPVL, VD was independently associated with an increased risk of IVH (odds ratio [OR] 1.600[1.423-1.799], p <0.001) and its complications (OR 1.440[1.195-1.735], p <0.001). MOD was not associated with an increased risk of cPVL. Our study suggests that CS is associated with a reduced risk of IVH and its complications in preterm VLBW infants < 32 weeks of gestational age. A CS should be considered in this group of infants to prevent the development of IVH and its complications. · IVH and cPVL are risk factors for neurological disabilities.. · CS may decrease the risk of IVH in preterms <32 weeks GA.. · There is no association between the MOD and cPVL..


Characterization of inflammatory factor-induced changes in mesenchymal stem cell exosomes and sequencing analysis of exosomal microRNAs.
Treatments utilizing stems cells often require stem cells to be exposed to inflammatory environments, but the effects of such environments are unknown. To examine the effects of inflammatory cytokines on the morphology and quantity of mesenchymal stem cell exosomes (MSCs-exo) as well as the differential expression of microRNAs (miRNAs) in the exosomes. MSCs were isolated from human umbilical tissue by enzymatic digestion. Exosomes were then collected after a 48-h incubation period in a serum-free medium with one of the following the inflammatory cytokines: None (control), vascular cell adhesion molecule-1 (VCAM-1), tumor necrosis factor (TNF) α, and interleukin (IL) 6. The morphology and quantity of each group of MSC exosomes were observed and measured. The miRNAs in MSCs-exo were sequenced. We compared the sequenced data with the miRBase and other non-coding databases in order to detect differentially expressed miRNAs and explore their target genes and regulatory mechanisms. In vitro tube formation assays and Western blot were performed in endothelial cells which were used to assess the angiogenic potential of MSCs-exo after inflammatory cytokine stimulation. MSCs-exo were numerous, small, and regularly shaped in the VCAM-1 group. TNFα stimulated MSCs to secrete larger and irregular exosomes. IL6 led to a reduced quantity of MSCs-exo. Compared to the control group, the TNFα and IL6 groups had more downregulated differentially expressed miRNAs, particularly angiogenesis-related miRNAs. The angiogenic potential of MSCs-exo declined after IL6 stimulation. TNFα and IL6 may influence the expression of miRNAs that down-regulate the PI3K-AKT, MAPK, and VEGF signaling pathways; particularly, IL6 significantly down-regulates the PI3K-AKT signaling pathway. Overall, inflammatory cytokines may lead to changes in exosomal miRNAs that abnormally impact cellular components, molecular function, and biological processes.


Mito-TEMPO mitigates 5-fluorouracil-induced intestinal injury via attenuating mitochondrial oxidative stress, inflammation, and apoptosis: an in vivo study.
Recent evidences highlight role of mitochondria in the development of 5-fluorouracil (5-FU)-induced intestinal toxicity. Mitochondria-targeted antioxidants are well-known for their protective effects in mitochondrial oxidative stress- mediated diseases. In the present study, we investigated protective effect of Mito-TEMPO in 5-FU-induced intestinal toxicity. Mito-TEMPO (0.1 mg/kg b.w.) was administered intraperitoneally to male BALB/c mice for 7 days, followed by co-administration of 5-FU for next 4 days (intraperitoneal 12 mg/kg b.w.). Protective effect of Mito-TEMPO on intestinal toxicity was assessed in terms of histopathological alterations, modulation in inflammatory markers, apoptotic cell death, expression of 8-OhDG, mitochondrial functional status and oxidative stress. 5-FU administered animals showed altered intestinal histoarchitecture wherein a shortening and atrophy of the villi was observed. The crypts were disorganized and inflammatory cell infiltration was noted. Mito-TEMPO pre-protected animals demonstrated improved histoarchitecture with normalization of villus height, better organized crypts and reduced inflammatory cell infiltration. The inflammatory markers and myeloperoxidase activity were normalized in mito-TEMPO protected group. A significant reduction in intestinal apoptotic cell death and expression of 8-OhDG was also observed in mito-TEMPO group as compared to 5-FU group. Further, mtROS, mtLPO and mitochondrial antioxidant defense status were improved by mito-TEMPO. Mito-TEMPO exerted significant protective effect against 5-FU-induced intestinal toxicity. Therefore, it may be used as an adjuvant in 5-FU chemotherapy.


Increased 99mTc-pyrophosphate uptake with radiation pneumonitis.
A case of radiation pneumonitis confirmed by tissue biopsy is presented with demonstration of increased uptake of 99mTc-pyrophosphate.


P-Body Purification Reveals the Condensation of Repressed mRNA Regulons.
Within cells, soluble RNPs can switch states to coassemble and condense into liquid or solid bodies. Although these phase transitions have been reconstituted in vitro, for endogenous bodies the diversity of the components, the specificity of the interaction networks, and the function of the coassemblies remain to be characterized. Here, by developing a fluorescence-activated particle sorting (FAPS) method to purify cytosolic processing bodies (P-bodies) from human epithelial cells, we identified hundreds of proteins and thousands of mRNAs that structure a dense network of interactions, separating P-body from non-P-body RNPs. mRNAs segregating into P-bodies are translationally repressed, but not decayed, and this repression explains part of the poor genome-wide correlation between RNA and protein abundance. P-bodies condense thousands of mRNAs that strikingly encode regulatory processes. Thus, we uncovered how P-bodies, by condensing and segregating repressed mRNAs, provide a physical substrate for the coordinated regulation of posttranscriptional mRNA regulons.


Systemic lupus erythematosus, lupus nephritis and end-stage renal disease: a pragmatic review mapping disease severity and progression.
The understanding of systemic lupus erythematosus (SLE) and lupus nephritis (LN) pathogenesis remains incomplete. This review assessed LN development in SLE, within-LN progression and progression to end-stage renal disease (ESRD). A keyword-based literature search was conducted, and 26 publications were included. Overall, 7-31% of patients had LN at SLE diagnosis; 31-48% developed LN after SLE diagnosis, most within 5 years. Class IV was the most commonly found LN class and had the worst prognosis. Histological transformation occurred in 40-76% of patients, more frequently from non-proliferative rather than proliferative lesions. Cumulative 5- and 10-year ESRD incidences in patients with SLE were 3% and 4%, respectively, and 3-11% and 6-19%, respectively, in patients with SLE and LN. Elevated serum creatinine was identified as a predictor of worsening disease state, and progression within LN classes and from SLE/LN to ESRD. This review highlights the substantial risk for developing LN and progressing to ESRD amongst patients with SLE.


Identification of 100 KDa protein in sera of mice-treated with Cu(II) complex with superoxide dismutase-mimetic activity.
The protein profile of sera isolated from mice pre-treated with Cu(II) complex of Girard T with superoxide dismutase (SOD)-mimetic activity was analyzed using SDS-PAGE. This complex was intraperitoneally administered (10 mg/Kg body weight) to Swiss albino mice. The resolved polypeptides showed a new sharp band at 100 KDa against which a polyclonal antibody was raised in rabbit. Sera of rabbit anti-100 KDa protein was used as a powerful probe for the detection of 100 KDa protein isolated from sera of treated mice. Western blot assays revealed a strong reactive polypeptide band at 100 KDa in sera of the mice, but no cross reaction was observed with sera of normal mice. The identification of purified polypeptide was confirmed by different characterization experiments.


Synergistic and simultaneous biosorption of phenanthrene and iodine from aqueous solutions by soil indigenous bacterial biomass as a low-cost biosorbent.
The removal of phenanthrene and iodine from aqueous solutions in single and binary systems by inactivated soil indigenous bacterial biomass (SIBB), as well as affecting factors, were evaluated. Sorption kinetic and isotherm studies were carried out to investigate the synergistic effects of phenanthrene and iodine. Optimal parameters for the biosorption process included a solution pH of 6.0 and biosorbent dosage of 0.75 g L-1. The ionic strength significantly decreased the biosorption of both phenanthrene and iodine in single conditions, while no obvious influences were found in the binary conditions. A pseudo-second-order model was well fitted to the kinetic biosorption data for both phenanthrene and iodine. The results showed that the presence of co-solute accelerated the biosorption processes and the pseudo-second-order biosorption rates (k 2) for phenanthrene and iodine increased from 0.005441 to 0.009825 g mg-1 min-1 and from 0.000114 to 0.000223 g mg-1 min-1, respectively. The SIBB showed strong affinity with both phenanthrene and iodine, with a partition coefficient K d (Linear model) of 6892.4 L kg-1 for phenanthrene and affinity parameter K L (Langmuir model) of 232 500 L kg-1 for iodine. The presence of co-solute illustrated a synergistic effect on the biosorption of phenanthrene and iodine due to intermolecular forces between phenanthrene and iodine, enhancing the K d of 34.7% for phenanthrene and K L of 107.0% for iodine, respectively. The results suggested that SIBB was an effective material for the simultaneous biosorption of phenanthrene and iodine from aqueous solutions.


Distribution and morphology of abducens motoneurons innervating the lateral rectus and retractor bulbi muscles in the frog Rana ridibunda.
The distribution and morphology of the neurons innervating the lateral rectus and retractor bulbi muscles of the frog Rana ridibunda were studied by means of retrograde axonal transport of horseradish peroxidase (HRP). The neurons are located in the rhombencephalon in two distinct groups which lie dorsolateral and lateral to the fasciculus longitudinalis medialis and represent the main and accessory abducens nuclei, respectively. From HRP injections into the two muscles, it can be concluded that multipolar neurons located rostrally in the main abducens nucleus innervate the lateral rectus muscle. The retractor bulbi muscle receives its innervation from bipolar, fusiform neurons located in the caudal portion of the main abducens nucleus and throughout the rostrocaudal extent of the accessory abducens nucleus.


Anoikis resistance--protagonists of breast cancer cells survive and metastasize after ECM detachment.
Breast cancer exhibits the highest global incidence among all tumor types. Regardless of the type of breast cancer, metastasis is a crucial cause of poor prognosis. Anoikis, a form of apoptosis initiated by cell detachment from the native environment, is an outside-in process commencing with the disruption of cytosolic connectors such as integrin-ECM and cadherin-cell. This disruption subsequently leads to intracellular cytoskeletal and signaling pathway alterations, ultimately activating caspases and initiating programmed cell death. Development of an anoikis-resistant phenotype is a critical initial step in tumor metastasis. Breast cancer employs a series of stromal alterations to suppress anoikis in cancer cells. Comprehensive investigation of anoikis resistance mechanisms can inform strategies for preventing and regressing metastatic breast cancer. The present review first outlines the physiological mechanisms of anoikis, elucidating the alterations in signaling pathways, cytoskeleton, and protein targets that transpire from the outside in upon adhesion loss in normal breast cells. The specific anoikis resistance mechanisms induced by pathological changes in various spatial structures during breast cancer development are also discussed. Additionally, the genetic loci of targets altered in the development of anoikis resistance in breast cancer, are summarized. Finally, the micro-RNAs and targeted drugs reported in the literature concerning anoikis are compiled, with keratocin being the most functionally comprehensive. Video Abstract.


In vivo rate of serotonin synthesis in brain and spinal cord of young, spontaneously hypertensive rats.
The accumulation of 5-hydroxytryptophan (5-HTP) following decarboxylase inhibition was measured in hypothalamus (HYP), pons-medulla (PM) and spinal cord (SC) of 4- and 8-week-old spontaneously hypertensive (SH) and normotensive (WKY) rats. Using this method, a significant increase in the in vivo activity of tryptophan hydroxylase was observed in the PM and SC of 4-week-old, but not 8-week-old SH rats. These findings show a transient elevation in rate of 5-HT synthesis prior to the onset of hypertension, which does not appear to continue during the maintenance phase.


Biotechnological approach of improving plant salt tolerance using antioxidants as markers.
Salt stress causes multifarious adverse effects in plants. Of them, production of reactive oxygen species (ROS) is a common phenomenon. These ROS are highly reactive because they can interact with a number of cellular molecules and metabolites thereby leading to a number of destructive processes causing cellular damage. Plants possess to a variable extent antioxidant metabolites, enzymes and non-enzymes, that have the ability to detoxify ROS. In the present review, the emphasis of discussion has been on understanding the role of different antioxidants in plants defense against oxidative stress caused by salt stress. The role of different antioxidants as potential selection criteria for improving plant salt tolerance has been critically discussed. With the advances in molecular biology and availability of advanced genetic tools considerable progress has been made in the past two decades in improving salt-induced oxidative stress tolerance in plants by developing transgenic lines with altered levels of antioxidants of different crops. The potential of this approach in counteracting stress-induced oxidative stress has been discussed at length in this review.


Respiratory responses of ducks to simulated altitude.
Domestic ducks were exposed to simulated altitudes of 0, 3000, 6000, and 9000 m in order to study the respiratory changes that take place. We found that the respiratory minute volume (VE,BTPS) increased with altitude, the increase being due to increased respiratory frequency while tidal volume (VT, BTPS) showed only minor changes. The quantity of air moved (VE, STPD), however, remained nearly unchanged with increasing altitude. The oxygen extraction, calculated as 1--(FIN2FEO2)/(FEN2FIO2), remained constant at about 0.28 up to 6000 m and declined to 0.17 at 9000 m. The fractional gas concentrations (FO2 and FCO2) in exhaled air and in the interclavicular and posterior thoracic air sacs changed only little up to 6000 m, but at 9000 m FO2 increased and FCO2 decreased. The relative constancy of expired and air sac gas up to 6000 m seems remarkable. However, when applied to current models of air flow in the avian respiratory system the results seem fully explainable and permit a detailed analysis of the functioning of the avian respiratory system.


1H, 13C, 15N backbone resonance assignment of Escherichia coli adenylate kinase.
Adenylate kinase reversibly catalyzes the conversion of ATP plus AMP to two ADPs. This essential catalyst is present in every cell, and the Escherichia coli protein is often employed as a model enzyme. Our aim is to use the E. coli enzyme to understand dry protein structure and protection. Here, we report the expression, purification, steady-state assay, NMR conditions and 1H, 13C, 15N backbone resonance NMR assignments of its C77S variant. These data will also help others utilize this prototypical enzyme.


Suction blister fluid as a model for interstitial fluid in rats.
1. Suction blisters on the skin of rats, obtained with a negative pressure of 150 mm Hg, show a close similarity to human suction blisters, based on histological, electrolyte and protein findings. 2. Pharmacokinetic experiments with inulin and antipyrine have proved that the movement of these low protein binding drugs between blister fluid and serum follows the laws of diffusion. 3. The investigations suggest that blister fluid resembles interstitial fluid and can therefore serve as a model for the estimation of drug concentrations in interstitial fluid.


Deep eutectic solvent-based liquid-phase microextraction coupled with reversed-phase high-performance liquid chromatography for determination of α-, β-, γ-, and δ-tocopherol in edible oils.
For simultaneous analysis of four fat-soluble tocopherols (α-, β-, γ-, and δ-) in edible oils, an efficient and green method using deep eutectic solvent-based liquid-phase microextraction (DES-LPME) coupled with reversed-phase high-performance liquid chromatography (RP-HPLC) was developed. The DESs formed by different quaternary ammonium salts and ethanol were used as the extractants. Tetrabutylammonium chloride (TBAC)-ethanol DES at a molar ratio of 1:2 achieved the best extraction efficiency. Under the optimized conditions, the detection limits were in the range of 2.1-3.0 ng mL-1. The intra-day and inter-day repeatability were in the ranges of 3.9-5.3% and 4.8-7.1%, respectively, and the recoveries for the real samples varied from 80.7% to 105.4%. The developed method was successfully employed for the determination of all four tocopherol homologues with an RP-HPLC system containing a COSMOSIL π-NAP column in five edible oils collected locally. Graphical abstract.


Chaoborus and fish-mediated influences on Daphnia longispina population structure, dynamics and life history strategies.
This study examined the long term effects of predation by larvae of the midge Chaoborus and simulated fish predation on experimental Daphnia longispina populations. Chaoborus predation, relative to fish predation, led to populations composed of larger individuals as a whole, larger egg-bearing individuals, and a larger primiparous instar. Daphnia retained helmets beyond the first instar in response to the presence of Chaoborus. Both types of predation, relative to predator-free controls, reduced prey population size and rates of increase, but increased population death rates. The reduction in population size due to predation led to increased resource availability for individuals remaining in the populations and increased individual fecundity in the predation treatments. The differences noted between the Chaoborus, fish, and control treatments increased with predation intensity.


Influence of rose anthocyanin extracts on physicochemical properties and in vitro digestibility of whey protein isolate sol/gel: Based on different pHs and protein concentrations.
Protein-polyphenol interactions can improve the physicochemical properties of proteins. The objective of this study was to investigate the influence of rose anthocyanin extracts (RAEs) on the physicochemical properties and digestibility of whey protein isolate (WPI) sol/gel at different pHs and protein concentrations. Hydrophobicity interaction and ionic bonding were the main forces for the formation of acidic WPI and WPI-RAEs sol/gel. When pH was higher than 2.4, sol/gel became unstable, which may be related to hydrophobicity, ζ-potential value, total sulfhydryl and free sulfhydryl content changes. In addition, RAEs had positive effects on the color and water distribution of all WPI sol/gel. Moreover, RAEs improved the viscoelasticity of WPI sol/gel with protein content ≥ 12 % (w/v) at pH 2.4. More importantly, the addition of RAEs could reduce the digestibility of WPI sol/gel. We hope our works can provide promising strategies for developing WPI-RAEs foods.


Evaluation of bone scan index change over time on automated calculation in bone scintigraphy.
Bone scintigraphy (bone scan) is useful in detecting metastatic bone lesions through visual assessment of hot spots. A semi-quantitative analysis method that evaluates bone scan images has been eagerly anticipated. BONENAVI is software that enables automatic assessment of bone scan index (BSI). BSI is useful for stratifying cancer patients and monitoring their therapeutic response. The purpose of this study was to evaluate the BONENAVI reading in determining BSI and hot spots at different time intervals after radioisotope injection. We evaluated 32 patients, including 22 males and 10 females. Ten patients had breast cancer, 20 patients had prostate cancer, and 2 had malignant pheochromocytoma. Patients were injected with 740 MBq of (99m)Tc-methylene diphosphonate and bone scintigraphy was performed at 2, 4, and 6 h after injection on each patient. The BSI and the number of hot spots were obtained from BONENAVI software. Bone scan images were also visually assessed to exclude false positives due to artifacts. Analyses were performed in all lesions, selected true lesions, segment based and cancer type based. Non-parametric statistical analyses for pairwise multiple group comparison were performed using Friedman test followed with post hoc analysis. The BSIs and the number of hot spots were significantly increased with time, with significant differences between each of time points (P < 0.001). Analysis of regional BSI (rBSI) and hot spot number changes of selected 15 true lesions also showed similar increase (P < 0.001). In general, the pelvic segment was the most prone to rBSI changes and the chest segment was the most prone to hot spot number changes. Visual assessment showed that BONENAVI diagnosed some typical artifacts as metastases (hot spots). BONENAVI reading of BSIs and hot spot numbers was highly affected by acquisition time. In serial or follow-up examinations (in particular, for monitoring therapeutic efficacy), acquisition time should be fixed for each patient. Cautious interpretation should be made on segments with high physiological uptake. BONENAVI reading was prone to misinterpretation of artifacts. Visual assessment is necessary to rule out this possibility.


Serum β2-microglobulin level is a useful indicator of disease activity and hemophagocytic syndrome complication in systemic lupus erythematosus and adult-onset Still's disease.
This study demonstrates whether serum β2-microglobulin (β2-MG) level can be an indicator of the status of systemic lupus erythematosus (SLE) and adult-onset Still's disease (AOSD), and development of hemophagocytic syndrome (HPS) complication. Serum β2-MG level was compared between the active and inactive statuses of SLE and AOSD in hospitalized patients. Active status was defined as a state for which a therapy was introduced. Serum β2-MG level was also compared between patients with and without HPS complication. HPS was diagnosed on the basis of clinical and pathological findings. Laboratory markers of HPS including peripheral blood cell counts and levels of serum lactate dehydrogenase (LDH), serum ferritin, plasma fibrin/fibrinogen degradation product (FDP), and plasma D-dimer were examined to determine their correlations with serum β2-MG level. Sixteen SLE and seven AOSD patients (all females, aged 39.0 ± 16.4) were included. The serum β2-MG level was high in the active status of underlying diseases and decreased significantly after the therapy (3.5 ± 1.4 vs. 2.1 ± 0.8 mg/L, p < 0.001). Among patients with active status, the β2-MG level was higher in patients with HPS (two with SLE and three with AOSD) than in patients without HPS (4.9 ± 1.8 vs. 3.3 ± 1.4 mg/L, p < 0.05). Serum β2-MG level significantly correlated with the levels of serum LDH (r(s) = 0.42, p < 0.05), plasma FDP (r(s) = 0.58, p < 0.05), and plasma D-dimer (r(s) = 0.77, p < 0.01). Serum β2-MG level would be a useful indicator of disease activity and development of HPS complication in patients with SLE and AOSD.


Solubilization of peripheral-type benzodiazepine binding sites from cat cerebral cortex.
The present study demonstrates for the first time the solubilization of peripheral-type benzodiazepine binding sites (PBS) from cat cerebral cortex. Of all detergents tested [digitonin, 3-[(3-cholamidopropyl)dimethylammonio]-1-propane sulfonate (CHAPS), Tween 20, deoxycholate, and Triton X-100] in the presence of NaCl, the best solubilization (15% of initial activity) was obtained using 0.5% of the zwitterionic detergent CHAPS plus 2 M NaCl. Specific binding of [3H]PK 11195 to membrane-bound and solubilized PBS was saturable, yielding equilibrium dissociation constants (KD) of 1.3 +/- 0.2 and 1.9 +/- 0.3 nM, respectively, and maximal numbers of binding sites of 1,435 +/- 150 and 980 +/- 126 fmol/mg protein, respectively. The KD value of PK 11195 binding to solubilized PBS obtained from experimental kinetic analysis was 0.95 +/- 0.09 nM. The relative potencies of various compounds (PK 11195, Ro 5-4864, diazepam, flunitrazepam, clonazepam, methyl-beta-carboline-3-carboxylate, and Ro 15-1788) in displacing [3H]PK 11195 specific binding from membrane-bound and solubilized PBS were similar. Most of the solubilized binding activity was destroyed by heating at 60 degrees C for 30 min or by treatment with 2 M guanidinium chloride, which indicates the presence of a protein-binding site in the solubilized preparation. Over 85% of the solubilized binding activity was retained after 1 week at 4 degrees C, which will enable future application of purification procedures without major concern for stability of the material.


Leiomyosarcoma of the inferior vena cava.
A 61-year-old woman with symptoms of inferior vena caval obstruction was investigated with computed tomography and ultrasound imaging and found to have a tumor of the inferior vena cava. Transvenous biopsy revealed a leiomyosarcoma, which at surgical exploration was considered to be unresectable. Autopsy showed that the tumor extended form its origin in the inferior vena cava just above the left renal vein to the right atrium. Hepatic metastases were documented. This rare tumor has seldom been diagnosed prior to exploratory surgery or necropsy and should be included in the differential diagnosis of inferior vena caval obstruction. The case illustrates the relative ease and efficacy of transvenous biopsy in establishing this diagnosis antemortem.


Clinical Significance of Endothelial Dysfunction in Essential Hypertension.
The endothelium is recognized as a major determinant of vascular physiology and pathophysiology. Over the last few decades, a plethora of studies have implicated endothelial dysfunction in the progression of atherosclerosis and the subclinical target organ damage observed in essential hypertension. However, the clinical significance of diagnosing endothelial dysfunction in patients with essential hypertension remains under investigation. Although a number of vascular and non-vascular markers of endothelial dysfunction have been proposed, there is an ongoing quest for a marker in the clinical setting that is optimal, inexpensive, and reproducible. In addition, endothelial dysfunction emerges as a promising therapeutic target of agents that are readily available in clinical practice. In this context, a better understanding of its role in essential hypertension becomes of great importance. Here, we aim to investigate the clinical significance of endothelial dysfunction in essential hypertension by accumulating novel data on (a) early diagnosis using robust markers with prognostic value in cardiovascular risk prediction, (b) the association of endothelial dysfunction with subclinical vascular organ damage, and (c) potential therapeutic targets.


Listening to speech-in-noise with hearing aids: Do the self-reported outcomes reflect the behavioral speech perception task performance?
The aim of this study is to examine the relationship between behavioral speech-in-noise listening tasks and self-reported speech-in-noise outcomes of hearing aid user adult listeners. To measure the self-reported outcomes of hearing, the Hearing Handicap Inventory for Adults [HHI-A], Speech, Spatial and Qualities of Hearing Scale (SSQ) and Amsterdam Inventory for Auditory Disability and Handicap were employed. To screen the cognitive abilities, Montreal Cognitive Assessment (MoCA) tool was used. Turkish matrix sentence test (TMST) was used for speech-in-noise test. Eighteen adult hearing aid users (mean age of 36.6 years) were participated. Results showed that some self-reported listening-in-noise outcomes are correlated with lab-based measurements of speech-in-noise test scores but not with the aided speech intelligibility thresholds. Given the present limitations of relying solely on self-report measures, it is important to complement them with objective measures to ensure a comprehensive evaluation.


Transcutaneous pacing for bradyasystolic cardiac arrests in prehospital care.
To test the efficacy of transcutaneous pacing in prehospital bradyasystolic arrest, we applied an external transcutaneous pacing device to patients with asystole, pulseless idioventricular rhythms (PIVR), and pulseless bradycardias. Pacemaker units were carried by emergency medical services (EMS) physicians and specially trained EMS personnel. Patients were followed to determine hospital course and outcome. Of the 112 patients evaluated, information to adequately document the presence or absence of electrical capture was available in 105 cases. Fifty-five (52%) of these cases demonstrated electrical capture; 9 of 112 patients (8%) recovered pulses. Of those in asystole, 26 of 50 (52%) showed electrical capture, while the rate was 60% for those with PIVR (24 of 40 patients) and complete heart block (CHB) (3 of 5 patients), and 25% for other pulseless bradycardias (2 of 8 patients). Pulses developed following capture in five of 55 patients (9%) in asystole and in four of 44 patients (9%) with PIVR. No patient with CHB or other bradycardias developed a pulse. No patients survived to be discharged from the hospital. The average time to application of the pacing device was 29 minutes after loss of pulse. Our data strongly suggest that delayed use of the transcutaneous pacing device does not improve the dismal survival rates of patients who suffer bradyasystolic cardiac arrest. Further studies should be directed toward investigating survival rates in patients paced immediately after the onset of cardiac arrest.


Management of primary cutaneous and metastatic melanoma.
To review the diagnosis, staging, and treatments (both standard and novel) for advanced melanoma and discuss the nursing role in the care of patients with melanoma. Published research and education articles, on-line journals, recent texts, and references from pertinent articles. Most melanomas are diagnosed at early localized stages when surgery alone can be curative. For patients diagnosed with metastatic disease, treatment options have been limited and generally considered ineffective. Recent developments in tumor genetics and a greater understanding of the role of the immune system in cancer have translated to better treatments. Nurses play a key role in ensuring that patients with melanoma understand their diagnosis, treatment recommendations (including supportive care, palliative chemotherapy, immunotherapies), and participation in clinical trials.


Gating kinetics and ligand sensitivity modified by phosphorylation of cardiac ryanodine receptors.
The effects of protein-kinase- (PKA-) dependent phosphorylation on the stationary gating kinetics of single ryanodine receptor (RyR) channels was defined. The single-channel activity from canine cardiac RyR was reconstituted into planar lipid bilayers. Exogenously applied PKA increased the single-channel open probability ( P(o)) of both native and purified cardiac RyR channels, after preincubation with ATP and Mg2+. The action of PKA on the RyR channel occurred only in the presence of ATP and adenosine 5'- O-(3-thiotriphosphate) (ATPgammaS), but not in the presence of 5'-adenylimidodiphosphate (AMP-PCP). Thus, the action of PKA requires the presence of a hydrolyzable ATP analog. PKA-induced channel activation was blocked by specific PKA inhibitors. All these results confirmed that the RyR channel can be phosphorylated by exogenous protein kinase. The gating kinetics of single RyR channels before PKA treatment were significantly altered by ATP and Mg2+ as physiological ligands. In contrast, after PKA treatment, neither ATP nor Mg2+ significantly alters the gating kinetics of these channels. PKA-dependent phosphorylation thus decreases the ATP and Mg2+ apparent sensitivity in most of the gating parameters of single RyR channels. The phosphorylated RyR channels open and close more frequently, stay open for longer, and stay closed for shorter periods. The dwell-time histograms obtained demonstrate that the phosphorylated and the dephosphorylated channels have strikingly different open and closed kinetics at physiological cytoplasmic concentrations of Mg and ATP.


A microgeographic analysis of physical activity behavior within elementary school grounds.
There is little scholarship on physical activity among children within outdoor spaces and work is needed to advance the design of these spaces from "best practices" towards evidence-based design. This project examined how playground feature density relates to children's physical activity. We used the System for Observing Play and Leisure Activity to observe children's physical activity. We observed children during school recess on 24 school grounds in the Denver metropolitan area of Colorado, in spring of 2010 and 2011. A total of 31,069 observations were made from an estimated 9900 children aged 5 to 12. These were aggregated and analyzed in 397 playground zones. We examined utilization, the number of children present in a particular activity zone during an observation, and the percentage of children engaged in moderate to vigorous physical activity as they relate to the density of constructed features on school playgrounds. Ordinary least-squares linear regression model assessed the relationship between playground feature density and the utilization and moderate to vigorous physical activity. Significant positive associations were observed between utilization and feature density among all children (β = .20; p < .001) and a statistically significant but small association was observed between moderate to vigorous physical activity and feature density for girls (β = .12; p = .013), but not for boys. This analysis contributes to evidence that design features of play spaces may influence children's behavior within school grounds.


The Electrical Isolation of the Left Atrial Posterior Wall in Catheter Ablation of Persistent Atrial Fibrillation.
This study explored whether complete electrical isolation of the left atrial (LA) posterior wall improves the rhythm outcome of catheter ablation of persistent atrial fibrillation (AF). Although the STAR AF2 (Substrate and Trigger Ablation for Reduction of Atrial Fibrillation Trial Part II) proved no additional benefit of empirical extra-pulmonary vein (PV) LA ablation, the long-term recurrence rate after circumferential PV isolation (CPVI) alone remains high. We randomly assigned 217 patients with persistent AF (83.1% men, age 58.7 ± 10.8 years, 73.3% long-standing persistent AF) to ablation with CPVI alone (CPVI group) or CPVI with a POsterior wall Box Isolation (POBI group). The endpoint of the POBI group was the elimination of the posterior atrial potentials by roof and posterior inferior lines and touch-up focal ablation. After a mean follow-up of 16.2 ± 8.8 months, the clinical recurrence rate did not significantly differ between the 2 groups (23.8% vs. 26.5%; p = 0.779) in the CPVI and POBI groups. The recurrence rate for atrial tachycardias (16.0% vs. 11.1%; p = 0.913) and cardioversion rates (6.7% vs. 13.7%; p = 0.093) to control clinical recurrences also did not significantly differ between the 2 groups. At the final follow-up, sinus rhythm was maintained without antiarrhythmic drug in 50.5% and 55.9% in the CPVI and POBI groups, respectively (p = 0.522). No significant difference was found in the major complication rates between the 2 groups, but the total ablation time was significantly longer in the POBI group (4,289 ± 1,837 s vs. 5,365 ± 2,358 s; p < 0.001). In patients with persistent AF, an empirical complete POBI did not improve the rhythm outcome of catheter ablation or influence the type of recurrent atrial arrhythmia. (Comparison of Circumferential Pulmonary Vein Isolation Alone Versus Linear Ablation in Addition to Circumferential Pulmonary Vein Isolation for Catheter Ablation in Persistent Atrial Fibrillation: Prospective Randomized Controlled Trial; NCT02721121).


Triterpene glycosides from sea cucumbers and their biological activities.
Triterpenoid glycosides are abundantly present in sea cucumbers, which are responsible for the toxicity of these echinoderms. More than 100 triterpenoid glycosides have been isolated in the past 20 years and those are grouped into four main structural categories considering their aglycone structure: 3β-hydroxyholost-9(ll)-ene aglycone skeleton, 3β-hydroxyholost-7-ene skeleton, other holostane type aglycones and nonholostane aglycone. Most of the triterpenoid glycosides are found to be possessing potential biological activities. Among the biological activities, anticancer activity and antiviral activity are the most widely studied areas. In this communication, we have presented a general view of the structural characteristics of triterpenoid glycosides and their major biological activities. The structural significance and the application limitations of triterpene glycosides are also discussed.


Two-level fixation with headless compression screws for tibial plateau fractures.
Reduction and fixation of tibial plateau fractures associated with small, "floating" intra-articular fragments proposes a challenge. We use fully threaded headless compression screws for (interfragmentary) fixation of such fragments before final plate fixation when standard fixation of intra-articular fragments with k-wires or lag screws is deemed insufficient. Our aim is to describe our technique and clinical experience of this two-level fixation. Between 2006 and 2021, 29 patients with a comminuted tibial plateau fracture were treated with this two-level fixation in this retrospective case series. Clinical baseline and surgical variables were collected for all patients. Clinical outcome variables were available for 28 patients with a median follow-up of 16.5 months (IQR 5-24). Functional outcomes were measured with the Knee Injury and Osteoarthritis Outcome Score (KOOS) and reported by 22 patients at a median of 5.2 years (IQR 3.5-9.8). Reduction was anatomic or good in 82% of cases, fair in 14%, and a malreduction in 4%. Arthrosis was graded as grade 0 in 25% of cases, 1 in 39%, 2 in 21%, and 3 in 14%. Flexion was 110 degrees (IQR 100-130). Five patients had an extension deficit of 5 to 10 degrees. Median KOOS for symptoms and stiffness was 69 points (IQR 45-78), for pain 71 (IQR 45-88), for ADL 85 (IQR 52-95), for sports 30 (IQR 11-55), and for quality of life 34 (IQR 19-56). The use of fully threaded headless compression screws is a simple and helpful addition in the treatment of comminuted tibial plateau fractures.


Therapeutic applications of zebrafish (Danio rerio) miRNAs linked with human diseases: A prospective review.
MicroRNAs (miRNAs) are the class of small, non-coding RNAs that are produced from precursor transcripts by subsequent processing steps mediated by members of the RNaseIII family, Dicer and Drosha protein within cell. The importance of zebrafish miRNAs in regulation of normal cellular development and support to various kinds of metabolism process. Although the zebrafish model provides a fundamental platform for the study of developmental biology but recent work with zebrafish model has expanded its appliance to a broad range of experimental studies relevant to different kind of human diseases. Presently, the zebrafish model is used for the study of cardiovascular disease, schizophrenia, bipolar I disorder in eyes, psoriasis, spinal cord injury, cancer and diabetes that showing in some selected miRNAs are regulate these diseases in molecular levels. Here, a superior drive performed to depict the fundamental utilization of the zebrafish miRNAs that targeted to several clinical diseases connected to human. This review aims to provide a summary of understanding of the cellular mechanism which is responsible for selected diseases and suggests some therapeutic application for inhibition of miRNA functions.


Prognostic value of preoperative serum gamma-glutamyltranspeptidase in patients with hepatocellular carcinoma after hepatectomy.
Gamma-glutamyltranspeptidase (γ-GGT), an oxidative stress marker, is correlated with inflammation in the extracellular hepatic microenvironment. This study aimed to evaluate the prognostic value of serum γ-GGT levels in patients with hepatocellular carcinoma (HCC) after hepatectomy. Three hundred and eight patients who underwent hepatic resection for HCC were included in the study. Preoperative serum γ-GGT levels, as well as demographic, clinical, and pathologic data, were analyzed. The optimal cutoff value of γ-GGT was 88 U/L. All patients were divided into γ-GGT ≤ 88 U/L group (n = 146) and γ-GGT > 88 U/L group (n = 162). The disease-free survival (DFS) and overall survival (OS) rates of patients in the γ-GGT > 88 U/L group were poorer than those in γ-GGT ≤ 88 U/L group. Preoperative serum γ-GGT levels, associating with gender, HBsAg status, tumor size, capsulation, tumor number, and vascular invasion, was an independent prognostic predictor of disease-free survival [hazard ratio (HR) = 1.616; 95 % confidence interval (CI), 1.223-2.135; P = 0.001] and overall survival (HR = 2.043; 95 % CI, 1.509-2.766; P < 0.001). Furthermore, γ-GGT was also associated with DFS and OS in small HCC (tumor size ≤5 cm) and alpha-fetoprotein (AFP) ≤ 200 ng/mL subgroup. In conclusion, γ-GGT is a promising and reliable prognostic biomarker in HCC patients after hepatic resection, especially for patients with small HCC or AFP ≤ 200 ng/mL.


Impact of an electronic tool in prescribing primary prophylaxis with ciprofloxacin or granulocyte colony-stimulating factor for breast cancer patients receiving TC chemotherapy.
The US Oncology Trial 9735 (doxorubicin and cyclophosphamide (AC) versus docetaxel and cyclophosphamide (TC)) reported febrile neutropenia (FN) in 5 % of patients receiving TC chemotherapy, in the absence of routine primary prophylaxis with granulocyte colony-stimulating factor (G-CSF) or antibiotics. In contrast, higher rates of FN have been reported in the 'real world' setting. This retrospective study compares the incidence and severity of FN and other TC-related toxicities before and after implementation of a primary prophylaxis computerized prescribing tool. Medical records of 207 patients receiving adjuvant TC between May 1, 2006, and November 1, 2011, were reviewed for toxicity. The incidence for each TC adverse event was measured by an incident rate ratio (IRR), and chi-square analysis was used to compare the differences in severity of TC toxicities before and after use of a primary prophylaxis computerized prescribing tool, and to compare G-CSF and ciprofloxacin groups. The implementation of a computerized prescribing tool significantly increased the proportion of patients prescribed primary prophylaxis (18.2 vs. 97.4 %; p < 0.001). Prior to the change in practice, the incidence of FN (incidence rate ratio 3.87; 95 % CI [1.3, 11.5]) and neutropenia (OR 4.8; 95 % CI [2.0, 11.7]) was significantly higher. Primary prophylaxis significantly reduced the rate of febrile neutropenia (20 vs. 5.3 %, p = 0.003). No significant differences were found in incidence and severity of other TC-related toxicities. Patients who did not receive G-CSF were at a greater risk for neutropenia (OR 5.1, 95 % CI [1.06, 24.3]). There were insufficient patients treated with antibiotics alone to compare to those treated with G-CSF. Implementation of a computerized prescribing tool significantly increased the use of primary prophylaxis by treating physicians in patients receiving TC chemotherapy, which was associated with reduced incidence of febrile neutropenia. Further research efforts should focus on the incorporation and routine use of evidence-based practices using tools such as alerts and prompts, in order to optimize patient care and improve outcomes.


Esculentin(1-21), an amphibian skin membrane-active peptide with potent activity on both planktonic and biofilm cells of the bacterial pathogen Pseudomonas aeruginosa.
Pseudomonas aeruginosa is an opportunistic bacterial pathogen that forms sessile communities, named biofilms. The non-motile forms are very difficult to eradicate and are often associated with the establishment of persistent infections, especially in patients with cystic fibrosis. The resistance of P. aeruginosa to conventional antibiotics has become a growing health concern worldwide and has prompted the search for new anti-infective agents with new modes of action. Naturally occurring antimicrobial peptides (AMPs) represent promising future template candidates. Here we report on the potent activity and membrane-perturbing effects of the amphibian AMP esculentin(1-21), on both the free-living and sessile forms of P. aeruginosa, as a possible mechanism for biofilm disruption. Furthermore, the findings that esculentin(1-21) is able to prolong survival of animals in models of sepsis and pulmonary infection indicate that this peptide can be a promising template for the generation of new antibiotic formulations to advance care of infections caused by P. aeruginosa.