A Recursive Subdivision Technique for Sampling Multi-class Scatterplots.
We present a non-uniform recursive sampling technique for multi-class scatterplots, with the specific goal of faithfully presenting relative data and class densities, while preserving major outliers in the plots. Our technique is based on a customized binary kd-tree, in which leaf nodes are created by recursively subdividing the underlying multi-class density map. By backtracking, we merge leaf nodes until they encompass points of all classes for our subsequently applied outlier-aware multi-class sampling strategy. A quantitative evaluation shows that our approach can better preserve outliers and at the same time relative densities in multi-class scatterplots compared to the previous approaches, several case studies demonstrate the effectiveness of our approach in exploring complex and real world data.


Effect of long-term vineyard monoculture on rhizosphere populations of pseudomonads carrying the antimicrobial biosynthetic genes phlD and/or hcnAB.
The impact of repeated culture of perennial plants (i.e. in long-term monoculture) on the ecology of plant-beneficial bacteria is unknown. Here, the influence of extremely long-term monocultures of grapevine (up to 1603 years) on rhizosphere populations of fluorescent pseudomonads carrying the biosynthetic genes phlD for 2,4-diacetylphloroglucinol and/or hcnAB for hydrogen cyanide was determined. Soils from long-term and adjacent short-term monoculture vineyards (or brushland) in four regions of Switzerland were baited with grapevine or tobacco plantlets, and rhizosphere pseudomonads were studied by most probable number (MPN)-PCR. Higher numbers and percentages of phlD(+) and of hcnAB(+) rhizosphere pseudomonads were detected on using soil from long-term vineyards. On focusing on phlD, restriction fragment length polymorphism profiling of the last phlD-positive MPN wells revealed seven phlD alleles (three exclusively on tobacco, thereof two new ones). Higher numbers of phlD alleles coincided with a lower prevalence of the allele displayed by the well-studied biocontrol strain Pseudomonas fluorescens F113. The prevalence of this allele was 35% for tobacco in long-term monoculture soils vs. >60% in the other three cases. We conclude that soils from long-term grapevine monocultures represent an untapped resource for isolating novel biocontrol Pseudomonas strains when tobacco is used as bait.


Striatal 5-HT1A receptor stimulation reduces D1 receptor-induced dyskinesia and improves movement in the hemiparkinsonian rat.
Convergent evidence suggests that serotonin 5-HT1A receptor (5-HT1AR) agonists reduce l-DOPA-induced dyskinesia by auto-regulating aberrant release of l-DOPA-derived dopamine (DA) from raphestriatal neurons. However, recent findings indicate that 5-HT1AR stimulation also modifies D1 receptor (D1R)-mediated dyskinesia and rotations implicating a previously unexplored extra-raphe mechanism. In order to characterize the contribution of the striatum to these effects, rats with medial forebrain bundle DA lesions were tested for abnormal involuntary movements (AIMs) and rotations following striatal microinfusions of the 5-HT1AR agonist +/-8-OH-DPAT and systemic D1R agonist treatment with SKF81297. Additional rats with multi-site striatal DA lesions were tested for motor disability following systemic or intrastriatal +/-8-OH-DPAT with or without systemic SKF81297. In rats with medial forebrain bundle lesions, striatal infusions of +/-8-OH-DPAT dose-dependently reduced AIMs while conversely increasing rotations. In rats with striatal lesions, +/-8-OH-DPAT alone, both systemic and intrastriatal administration, optimally reversed motor disability. Collectively, these results support an important functional interaction between 5-HT1AR and D1R in the striatum with implications for the improved treatment of Parkinson's disease.


Are there benefits or harm from pressure targeting during lung-protective ventilation?
Mechanically, breath design is usually either flow/volume-targeted or pressure-targeted. Both approaches can effectively provide lung-protective ventilation, but they prioritize different ventilation parameters, so their responses to changing respiratory-system mechanics and patient effort are different. These different response behaviors have advantages and disadvantages that can be important in specific circumstances. Flow/volume targeting guarantees a set minute ventilation but sometimes may be difficult to synchronize with patient effort, and it will not limit inspiratory pressure. In contrast, pressure targeting, with its variable flow, may be easier to synchronize and will limit inspiratory pressure, but it provides no control over delivered volume. Skilled clinicians can maximize benefits and minimize problems with either flow/volume targeting or pressure targeting. Indeed, as is often the case in managing complex life-support devices, it is operator expertise rather than the device design features that most impacts patient outcomes.


Treatment of experimental autoimmune uveoretinitis with intravitreal injection of tacrolimus (FK506) encapsulated in liposomes.
PURPOSE. To evaluate the effects of intravitreal injection of liposomes encapsulating tacrolimus (FK506) on experimental autoimmune uveoretinitis (EAU) in Lewis rats. METHODS. Liposomes containing tacrolimus were prepared by reverse-phase evaporation vesicles. EAU was induced in Lewis rats by subcutaneous injection of interphotoreceptor retinoid-binding protein R16 peptide emulsified in adjuvant. Ten days later, rats were intravitreally injected with saline, tacrolimus, tacrolimus-loaded liposomes, or unloaded liposomes. Clinical signs of inflammation and ocular histologic sections were observed and graded. Retinal function was evaluated by electroretinography (ERG). Tacrolimus concentration was determined in the vitreous body and serum by ELISA. Ocular biodistribution of rhodamine-conjugated liposomes containing tacrolimus (tacrolimus-Rh-lip) was analyzed with a laser scanning confocal microscope. To evaluate the systemic effect of intravitreally injected tacrolimus, delayed-type hypersensitivity (DTH) and lymphocyte proliferation assay (LPA) responses were detected. RESULTS. Treatment of EAU with intravitreal injection of liposomal tacrolimus significantly reduced intraocular inflammation and markedly inhibited the development of EAU, as determined in clinical and histopathologic analyses. No toxic effects could be detected as evaluated by ERG. The concentration of tacrolimus in ocular fluids remained for as long as 14 days after liposomal injection of tacrolimus. Confocal microscopy showed a transretinal distribution of the liposomal particles. DTH and LPA responses were not impaired in liposomal tacrolimus-treated rats. CONCLUSIONS. Intravitreal injection of liposomal tacrolimus was highly effective in suppressing the process of EAU without any side effects on retinal function or systemic cellular immunity. This treatment may represent a new option for the management of intraocular inflammation.


Synthesis and Photophysical Properties of Silole-Fused Cycloparaphenylenes.
Herein, we report the introduction of a silole unit into cycloparaphenylenes (CPPs), and two compounds [12]Si3CPP and [16]Si4CPP are obtained by a platinum- and gold-mediated cyclooligomerization strategy. Their optical and electronic properties are studied by UV-vis absorption and fluorescence spectra, which show red shifts and higher photoluminescence quantum yields (PLQYs) compared with the corresponding CPPs.


Effects of Kinect-based virtual reality game training on upper extremity motor recovery in chronic stroke.
Therapeutic benefits of Kinect-based virtual reality (VR) game training in rehabilitation encourage its use to improve motor function. To assess the effects of Kinect-based VR training on motor recovery of the upper extremity and functional outcomes in patients with chronic stroke. In this randomized controlled trial, group A received 20 sessions of physical therapy (PT) + 20 sessions of Kinect-based VR training and group B received only 20 sessions of PT. Clinical outcome measures were assessed at baseline and at the end of the treatments. Primary outcome measures that assess stroke patients' motor function included upper extremity (UE) Fugl-Meyer Assessment (FMA). Secondary outcome measures were Brunnstrom Recovery Stages (BRS), Modified Ashworth Scale (MAS), Box and Block test (BBT), Motricity index (MI), and active range of motion (AROM) measurement. Statistically significant improvements in game scores (p < 0.05) were observed in group A. In within-group analysis, there were statistically significant improvements in all clinical outcome measures except for the BRS-hand, MAS-distal, and MAS-hand in group A; MAS-(proximal, distal, hand) and BRS-(UE, hand) in group B compared with baseline values. Differences from baseline of FMA, MI, and AROM (except adduction of shoulder and extension of elbow) were greater in group A (p < 0.05). To conclude, our results suggest that the adjunct use of Kinect-based VR training may contribute to the improvement of UE motor function and AROM in chronic stroke patients. Further studies with a larger number of subjects with longer follow-up periods are needed to establish its effectiveness in neurorehabilitation.


The 1999 Balkan war: changes in ratings of values and prowar attitudes among French students.
This study investigated the association of Kosovo's 1999 war with a value rating of 56 female French students and links between values evaluated at two times (before and during the war) and attitudes towards the Balkan war. Subjects completed a survey of 15 values by means of a 9-point Likert-type scale one month before the beginning of the Balkan war (Time 1) and during the war, 3 mo. later (Time 2). Attitude towards the war was also measured by means of a 4-item scale completed at Time 2. Analysis indicated two slight unpredicted shifts: Universalism and Stimulation value-types were rated higher at Time 2 than at Time 1. Moreover, two value-types were consistently correlated both at Times 1 and 2 with prowar attitudes: conformity (r = .29 and .27) and universalism (r = -.29 and -.43). This latter result, consistent with our hypothesis, suggested that individuals' values represent modest but significant correlates of prowar attitudes.


Organ donation as an 'altruistic gift': incentives and reciprocity in deceased organ donation from a UK Polish migrant perspective.
Incentives and reciprocity have been widely debated within the literature as an alternative to altruism to motivate the public to register and consent to organ donation. This pilot study was the first to examine the views of the UK Polish migrant community toward these issues. One-to-one and small group interviews were conducted in English and Polish to collect data. The interviews were recorded and transcribed and interviews in Polish were translated into English. All transcripts were coded, codes were grouped by theme and emergent themes were constantly compared to the new data until saturation. Participants were motivated to donate altruistically but would accept reciprocity for organs once consent was given. Payment for organs was viewed as unfavourable but participants would accept contribution toward funeral expenses. Deceased organ donation was viewed as an 'altruistic gift'. 'Altruism' and 'gift' are problematic in deceased organ donation and could explain the challenges that arise in the incentives and reciprocity debate. Mauss's gift exchange theory could frame incentives as forming the 'obligation to give' and could encourage registration but could lead to coercion. Reciprocity could benefit families and be viewed as 'fair' and a token of gratitude.


Transcranial ultrasound (TUS) effects on mental states: a pilot study.
Transcranial ultrasound (TUS) can modulate brain function. To assess possible TUS modulation of mental states, we investigated effects on subjective reports of pain and mood of sub-thermal TUS versus placebo applied to frontal scalp and brain of chronic pain patient volunteers. With IRB approval and informed consent, subjects with chronic pain completed two visual analog scales for pain (NRS) and mood (VAMS/Global Affect), and their vital signs were recorded 10 min prior to, and 10 min and 40 min following exposure to either subthermal TUS (8 MHz) or placebo (in a double blind crossover study) using the 12L-RS probe of a LOGIQe ultrasound imaging machine (General Electric, USA). A physician, also blinded for TUS versus placebo, applied the probe (with gel) to scalp over posterior frontal cortex, contralateral to maximal pain, for 15 seconds. A second investigator operated the ultrasound machine, randomizing TUS versus placebo. The process was then repeated, applying the opposite modality (TUS or placebo). Subjective reports of Mood/Global Affect were improved 10 min (P = 0.03) and 40 min (P = 0.04) following TUS compared with placebo. NRS pain reports slightly improved following TUS (P = 0.07) at 40 min. We found improvement in subjective mood 10 min and 40 min after TUS compared to placebo. TUS can have safe neurophysiological effects on brain function, and is a promising noninvasive therapy for modulating conscious and unconscious mental states and disorders. We suggest TUS acts via intra-neuronal microtubules, which apparently resonate in TUS megahertz range.


Evolution of the Vertebrate Resistin Gene Family.
Resistin (encoded by Retn) was previously identified in rodents as a hormone associated with diabetes; however human resistin is instead linked to inflammation. Resistin is a member of a small gene family that includes the resistin-like peptides (encoded by Retnl genes) in mammals. Genomic searches of available genome sequences of diverse vertebrates and phylogenetic analyses were conducted to determine the size and origin of the resistin-like gene family. Genes encoding peptides similar to resistin were found in Mammalia, Sauria, Amphibia, and Actinistia (coelacanth, a lobe-finned fish), but not in Aves or fish from Actinopterygii, Chondrichthyes, or Agnatha. Retnl originated by duplication and transposition from Retn on the early mammalian lineage after divergence of the platypus, but before the placental and marsupial mammal divergence. The resistin-like gene family illustrates an instance where the locus of origin of duplicated genes can be identified, with Retn continuing to reside at this location. Mammalian species typically have a single copy Retn gene, but are much more variable in their numbers of Retnl genes, ranging from 0 to 9. Since Retn is located at the locus of origin, thus likely retained the ancestral expression pattern, largely maintained its copy number, and did not display accelerated evolution, we suggest that it is more likely to have maintained an ancestral function, while Retnl, which transposed to a new location, displays accelerated evolution, and shows greater variability in gene number, including gene loss, likely evolved new, but potentially lineage-specific, functions.


Patient compliance to individualized home exercise programs.
Of individuals prescribed individualized home exercise programs, 55.2 percent continued to achieve greater than 75 percent of thier exercising goal after 32 weeks of participation. A method of predicting compliance early in the course of an exercise program is presented. The parameters as outlined were successful in correctly predicting by four weeks of participation the level of compliance in 89.6 percent of the individuals in this program. Family physicians should therefore be encouraged to prescribe exercise for their patients with the expectation of a significant compliant response. Early predictability also provides the physician the opportunity of intervention and modification of the program to further enhance compliance.


[Digital subtraction angiography of the aorta].
The results of 300 digital subtraction angiographies of the thoracic and abdominal aorta are analysed. Following intraarterial injection of contrast, all examinations were of good quality. Following I-V DSA, two thoracic (1.8%) and two abdominal (1.2%) aortograms were non-diagnostic. Anomalies in the position of the aorta, dilatation (aneurysm) or stenoses (coarctations, arteriosclerosis, occlusions) could be diagnosed by I-V DSA. One I-A DSA was performed for aneurysm of the ascending aorta in order to evaluate function of the aortic valve and for demonstrating the coronary artery origins, and pre-operatively for an aortic dissection.


Sleep improves the variability of motor performance.
Sleep after learning often enhances task performance, but the underlying mechanisms remain unclear. Using a well-characterized rotation learning paradigm implemented both behaviorally and in computer simulations, we compared two main hypotheses: the first, that off-line replay during sleep leads to further potentiation of synaptic circuits involved in learning; the second, that sleep enhances performance by uniformly downscaling synaptic strength. A simple computer model implemented synaptic changes associated with rotation adaptation (30 degrees ), yielding a reduction in mean directional error. Simulating further synaptic potentiation led to a further reduction of mean directional error, but not of directional variability. By contrast, simulating sleep-dependent synaptic renormalization by scaling down all synaptic weights by 15% decreased both mean directional error and variability. Two groups of subjects were tested after either two rotation adaptation training sessions or after a single training session followed by sleep. After two training sessions, mean direction error decreased, but directional variability remained high. However, subjects who slept after a single training session showed a reduction in both directional error and variability, consistent with a downscaling mechanism during sleep.


Complex sarcolemmal invaginations mimicking myotendinous junctions in a case of Laing early-onset distal myopathy.
Distal myopathies are a group of clinically and pathologically overlapping muscle diseases that are genetically complex and can represent a diagnostic challenge. Laing early-onset distal myopathy (MPD1) is a form of distal myopathy caused by mutations in the MYH7 gene, which encodes the beta myosin heavy chain protein expressed in type 1 skeletal muscle fibers and cardiac myocytes. Here, we present a case of genetically confirmed MPD1 with a typical clinical presentation but distinctive light microscopic and ultrastructural findings on muscle biopsy. A 39-year-old professional male cellist presented with a bilateral foot drop that developed by age 8; analysis of the family pedigree showed an autosomal dominant pattern of inheritance. The physical exam demonstrated bilateral weakness of ankle dorsiflexors, toe extensors and finger extensors; creatine kinase level was normal. Biopsy of the quadriceps femoris muscle showed predominance and hypotrophy of type 1 fibers, hybrid fibers with co-expression of slow and fast myosin proteins (both in highly atrophic and normal size range), moth-eaten fibers and mini-cores, lack of rimmed vacuoles and rare desmin-positive eosinophilic sarcoplasmic inclusions. In addition to these abnormalities often observed in MPD1, the biopsy demonstrated frequent clefted fibers with complex sarcolemmal invaginations; on ultrastructural examination, these structures closely mimicked myotendinous junctions but were present away from the tendon and were almost exclusively found in type 1 fibers. Sequencing analysis of the MYH7 gene in the index patient and other affected family members demonstrated a previously described heterozygous c.4522_4524delGAG (p.Glu1508del) mutation. This case widens the pathologic spectrum of MPD1 and highlights the pathologic and clinical variability that can accompany the same genetic mutation, suggesting a significant role for modifier genes in MPD1 pathogenesis.


Vitamin K antagonists predispose to calciphylaxis in patients with end-stage renal disease.
Calciphylaxis is associated with a poor prognosis in dialysis patients, and its pathogenesis remains incompletely understood. Although the use of vitamin K antagonists (VKA) has been implicated, previous reports are conflicting. We aimed to determine if vitamin K antagonists conferred an increased risk of calciphylaxis in patients on dialysis. We performed a single-centre, retrospective cohort study of 2,234 patients receiving dialysis, and compared the characteristics of those with and without calciphylaxis. We identified 5 cases of calciphylaxis (all female) between January 2009 and December 2013. Overall, 142 patients (6.4%) were treated with VKA during the study period. Calciphylaxis was more common in the VKA group (4 of 142 patients, OR = 61, 95% CI 6.7-546, p = 0.0001). VKA was withdrawn in all cases and treatment instituted with sodium thiosulphate, cinacalcet and supportive measures. All patients recovered, although there was one sudden cerebrovascular death during follow-up. Treatment with VKA predisposes to the development of calciphylaxis.


Isotope fractionation associated with the biodegradation of 2- and 4-nitrophenols via monooxygenation pathways.
Monooxygenation is an important route of nitroaromatic compound (NAC) biodegradation and it is widely found for cometabolic transformations of NACs and other aromatic pollutants. We investigated the C and N isotope fractionation of nitrophenol monooxygenation to complement the characterization of NAC (bio)degradation pathways by compound-specific isotope analysis (CSIA). Because of the large diversity of enzymes catalyzing monooxygenations, we studied the combined C and N isotope fractionation and the corresponding (13)C- and (15)N-apparent kinetic isotope effects (AKIEs) of four nitrophenol-biodegrading microorganisms (Bacillus spharericus JS905, Pseudomonas sp. 1A, Arthrobacter sp. JS443, Pseudomonas putida B2) in the pH range 6.1-8.6 with resting cells and crude cell extracts. While the extent of C and N isotope fractionation and the AKIE-values varied considerably for the different organisms, the correlated C and N isotope signatures (δ(15)N vs δ(13)C) revealed trends, indicative of two distinct monooxygenation pathways involving hydroxy-1,4-benzoquinone or 1,2- and 1,4-benzoquinone intermediates, respectively. The distinction was possible based on larger secondary (15)N-AKIEs associated with the benzoquinone pathway. Isotope fractionation was neither masked substantially by nitrophenol speciation nor transport across cell membranes. Only when 4-nitrophenol was biodegraded by Pseudomonas sp. 1A did isotope fractionation become negligible, presumably due to rate-limiting substrate binding steps pertinent to the catalytic cycle of flavin-dependent monooxygenases.


The influence of pre and postnatal adversity on depression and anxiety over two decades.
Perinatal and later postnatal adversity (e.g., child sexual abuse) are predictors of psychopathology across the lifespan. However, little is known about the impact of the joint effects of perinatal and postnatal adversity on the longitudinal trajectories of mental health problems from adolescence through adulthood. We utilized data from a prospective, longitudinal birth cohort of extremely low birth weight (ELBW; < 1000 g) survivors and normal birth weight (NBW; > 2500 g) control participants. Self-report data on internalizing (depression, anxiety) and externalizing (antisocial) problems were collected at 12-16, 22-26, and 30-35 years of age. A birth weight by child sexual abuse (CSA) interaction was observed such that ELBW survivors exposed to CSA had higher levels of internalizing problems from adolescence through adulthood than NBW participants exposed to CSA. Differences remained significant after adjustment for covariates. Likewise, ELBW survivors exposed to CSA had higher levels of internalizing problems from adolescence through adulthood than ELBW participants who were not exposed to CSA. Findings are limited by sample attrition due to the longitudinal nature of the study spanning over 30 years as well as the retrospective nature of child sexual abuse reporting. Exposure to both perinatal and later postnatal adversity leads to persistently higher internalizing problems than exposure to either adversity alone over more than two decades. These findings suggest that individuals exposed to perinatal adversity may be especially vulnerable to, and persistently affected by, childhood adversity, particularly in the form of depression and anxiety.


Topical diphenhydramine toxicity.
This paper will review an acute onset of mental confusion associated with hallucinations secondary to vigorous administration of topical Caladryl lotion and Benadryl spray in an 8-year-old boy with chickenpox. The article discusses the toxicity of both oral and topical diphenhydramine use, along with the differentiation of varicella encephalitis from diphenhydramine toxicity. Delirium can be described as an acute clouding of consciousness associated with visual and tactile hallucinations, disorientation, and misperceptions. In a child who is already suffering from an infectious illness, encephalitis must be high on the list of the physician's differential diagnosis. The physician, however, must never overlook ingestions, even from topical, over-the-counter medications. The case described illustrates this point. Although this appears to be the fourth case report on this subject, the diagnosis was partially obscured by the fact that the local pharmacist could not find any documented cases despite a computer search of diphenhydramine toxicity at the time of admission and the report of only one or two cases by the Parke-Davis pharmacist.


Loop Mediated Isothermal Amplification: Principles and Applications in Plant Virology.
In the last decades, the evolution of molecular diagnosis methods has generated different advanced tools, like loop-mediated isothermal amplification (LAMP). Currently, it is a well-established technique, applied in different fields, such as the medicine, agriculture, and food industries, owing to its simplicity, specificity, rapidity, and low-cost efforts. LAMP is a nucleic acid amplification under isothermal conditions, which is highly compatible with point-of-care (POC) analysis and has the potential to improve the diagnosis in plant protection. The great advantages of LAMP have led to several upgrades in order to implement the technique. In this review, the authors provide an overview reporting in detail the different LAMP steps, focusing on designing and main characteristics of the primer set, different methods of result visualization, evolution and different application fields, reporting in detail LAMP application in plant virology, and the main advantages of the use of this technique.


Supercoiling-induced DNA bending.
Local DNA bending is a critical factor for numerous DNA functions including recognition of DNA by sequence-specific regulatory binding proteins. Negative DNA supercoiling increases both local and global DNA dynamics, and this dynamic flexibility can facilitate the formation of DNA-protein complexes. We have recently shown that apexes of supercoiled DNA molecules are sites that can promote the formation of an alternative DNA structure, a cruciform, suggesting that these positions in supercoiled DNA are under additional stress and perhaps have a distorted DNA geometry. To test this hypothesis, we used atomic force microscopy to directly measure the curvature of apical positions in supercoiled DNA. The measurements were performed for an inherently curved sequence formed by phased A tracts and a region of mixed sequence DNA. For this, we used plasmids in which an inverted repeat and A tract were placed at precise locations relative to each other. Under specific conditions, the inverted repeat formed a cruciform that was used as a marker for the unambiguous identification of the A tract location. When the A tract and cruciform were placed diametrically opposite, this yielded predominantly nonbranched plectonemic molecules with an extruded cruciform and A tract localized in the terminal loops. For both the curved A tract and mixed sequence nonbent DNA, their localization to an apex increased the angle of bending compared to that expected for DNA unconstrained in solution. This is consistent with increased helical distortion at an apical bend.


Type II phosphatidylinositol 4-kinase regulates trafficking of secretory granule proteins in Drosophila.
Type II phosphatidylinositol 4-kinase (PI4KII) produces the lipid phosphatidylinositol 4-phosphate (PI4P), a key regulator of membrane trafficking. Here, we generated genetic models of the sole Drosophila melanogaster PI4KII gene. A specific requirement for PI4KII emerged in larval salivary glands. In PI4KII mutants, mucin-containing glue granules failed to reach normal size, with glue protein aberrantly accumulating in enlarged Rab7-positive late endosomes. Presence of PI4KII at the Golgi and on dynamic tubular endosomes indicated two distinct foci for its function. First, consistent with the established role of PI4P in the Golgi, PI4KII is required for sorting of glue granule cargo and the granule-associated SNARE Snap24. Second, PI4KII also has an unforeseen function in late endosomes, where it is required for normal retromer dynamics and for formation of tubular endosomes that are likely to be involved in retrieving Snap24 and Lysosomal enzyme receptor protein (Lerp) from late endosomes to the trans-Golgi network. Our genetic analysis of PI4KII in flies thus reveals a novel role for PI4KII in regulating the fidelity of granule protein trafficking in secretory tissues.


Pretransplant Desensitization with Costimulation Blockade and Proteasome Inhibitor Reduces DSA and Delays Antibody-Mediated Rejection in Highly Sensitized Nonhuman Primate Kidney Transplant Recipients.
Patients with broad HLA sensitization have poor access to donor organs, high mortality while waiting for kidney transplant, and inferior graft survival. Although desensitization strategies permit transplantation via lowering of donor-specific antibodies, the B cell-response axis from germinal center activation to plasma cell differentiation remains intact. To investigate targeting the germinal center response and plasma cells as a desensitization strategy, we sensitized maximally MHC-mismatched rhesus pairs with two sequential skin transplants. We administered a proteasome inhibitor (carfilzomib) and costimulation blockade agent (belatacept) to six animals weekly for 1 month; four controls received no treatment. We analyzed blood, lymph node, bone marrow cells, and serum before desensitization, after desensitization, and after kidney transplantation. The group receiving carfilzomib and belatacept exhibited significantly reduced levels of donor-specific antibodies (P=0.05) and bone marrow plasma cells (P=0.02) compared with controls, with a trend toward reduced lymph node T follicular helper cells (P=0.06). Compared with controls, carfilzomib- and belatacept-treated animals had significantly prolonged graft survival (P=0.02), and renal biopsy at 1 month showed significantly reduced antibody-mediated rejection scores (P=0.02). However, four of five animals with long-term graft survival showed gradual rebound of donor-specific antibodies and antibody-mediated rejection. Desensitization using proteasome inhibition and costimulation blockade reduces bone marrow plasma cells, disorganizes germinal center responses, reduces donor-specific antibody levels, and prolongs allograft survival in highly sensitized nonhuman primates. Most animals experienced antibody-mediated rejection with humoral-response rebound, suggesting desensitization must be maintained after transplantation using ongoing suppression of the B cell response.


Changing concepts in microsurgical pediatric varicocelectomy: is retroperitoneal approach better than subinguinal one?
To compare and to assess two different microsurgical "lymphatic-sparing" techniques (subinguinal/inguinal vs. retroperitoneal) used for the treatment of a pediatric and adolescent varicocele in terms of success rate, complications and mean operative time. A retrospective study included 54 consecutive patients affected by a varicocele and treated with a microsurgical (loupes--operating microscope) magnification. Thirty-four out of 54 (group 1) underwent subinguinal ligation with the help of loupes magnification (× 3); 20 out of 54 (group 2) underwent retroperitoneal (Palomo like) ligation with preservation of lymphatics and with the help of an operating microscope (× 6 to 10). The two groups were homogeneous in terms of mean age, clinical and color Doppler ultrasound grade of disease. Pre- and post-operative testicular volume was measured in all cases. All the procedures were performed under general anesthesia and in an outpatient basis. Mean post-operative follow-up time was 23.6 months. In group 1 we observed 3 (8.8%) early complications (wound's infection, transient hydrocele), 2 (5.8%) recurrences and 1 (2.9%) major complication (atrophy of the testis). Mean operative time was 45 +/- 6 min. In group 2 we did not observe complications and/or varicocele recurrence and mean operative time was 38 +/- 7 min. Comparison of mean operative time between the two groups resulted statistically significant differences (P < .05) such as the difference in testicular "catch-up" growth volume between pre- and post-operative evaluations. Retroperitoneal microsurgical "lymphatic-sparing" varicocelectomy is safe and effective method. In our experience, it is preferable, in the pediatric and adolescent patient, to the subinguinal/inguinal approach in terms of success rate, complications and operative time duration.


O-glycosylation as a novel control mechanism of peptidoglycan hydrolase activity.
Acm2, the major autolysin of Lactobacillus plantarum, is a tripartite protein. Its catalytic domain is surrounded by an O-glycosylated N-terminal region rich in Ala, Ser, and Thr (AST domain), which is of low complexity and unknown function, and a C-terminal region composed of five SH3b peptidoglycan (PG) binding domains. Here, we investigate the contribution of these two accessory domains and of O-glycosylation to Acm2 functionality. We demonstrate that Acm2 is an N-acetylglucosaminidase and identify the pattern of O-glycosylation (21 mono-N-acetylglucosamines) of its AST domain. The O-glycosylation process is species-specific as Acm2 purified from Lactococcus lactis is not glycosylated. We therefore explored the functional role of O-glycosylation by purifying different truncated versions of Acm2 that were either glycosylated or non-glycosylated. We show that SH3b domains are able to bind PG and are responsible for Acm2 targeting to the septum of dividing cells, whereas the AST domain and its O-glycosylation are not involved in this process. Notably, our data reveal that the lack of O-glycosylation of the AST domain significantly increases Acm2 enzymatic activity, whereas removal of SH3b PG binding domains dramatically reduces this activity. Based on this antagonistic role, we propose a model in which access of the Acm2 catalytic domain to its substrate may be hindered by the AST domain where O-glycosylation changes its conformation and/or mediates interdomain interactions. To the best of our knowledge, this is the first time that O-glycosylation is shown to control the activity of a bacterial enzyme.


Intraoperative monitoring of recurrent laryngeal nerve function.
Intraoperative recurrent laryngeal nerve identification is sometimes difficult in reoperative cervical dissection or operation for inflammatory thyroid disorders. Three modalities have been described to intraoperatively assess nerve function: vocal cord visualization with fiberoptic bronchoscopy or direct laryngoscopy, electromyelographic surveillance of arytenoid muscle function, and cord function assessment with an electromyelogram-electrode endotracheal tube. Our study focused on patients requiring cervical dissection for thyroid or parathyroid disease in which intraoperative recurrent laryngeal nerve function was monitored by nerve stimulation with a concentric bipolar probe. Impulses were tracked via a specialized electrode-bearing endotracheal tube with signal transduction to a recording monitor. No operative nerve injuries occurred in the patients of our study group. This surveillance technique's several advantages include use of standard intubation techniques with no increase in operative time, nerve stimulation tracings that are quantifiable and reproducible with production of a permanent record, and less subjectivity due to observer variability. We believe these factors make the electromyelogram-electrode endotracheal tube approach to intraoperative recurrent laryngeal nerve assessment the optimal technique.


[Tumor markers--how they should be applied].
Determination of a tumor marker is currently not suitable method for screening purpose (exception: PSA and thyroglobulin). Tumor marker determination cannot be employed to exclude the presence of a tumor. Prior to surgery, however, such determination is desirable, and in the case of germ cell tumors even mandatory. Postoperatively, or after termination of adjuvant chemotherapy and/or radiotherapy, determination of tumor markers as an individual baseline is necessary for the further disease course. During the course of the disease and for follow-up care, the kinetic development of tumor factors is, in comparison with the individual baseline values, of decisive importance. However, in order to ensue correct interpretation it is important to use the same test system.


Longitudinal analysis of the Alternative Healthy Eating Index-2010 and incident non-communicable diseases over 15 years in the 1973-1978 cohort of the Australian Longitudinal Study on Women's Health.
In studies that contain repeated measures of variables, longitudinal analysis accounting for time-varying covariates is one of the options. We aimed to explore longitudinal association between diet quality (DQ) and non-communicable diseases (NCDs). Participants from the 1973-1978 cohort of the Australian Longitudinal Study on Women's Health (ALSWH) were included, if they; responded to survey 3 (S3, 2003, aged 25-30 years) and at least one survey between survey 4 (S4, 2006) and survey 8 (S8, 2018), were free of NCDs at or before S3, and provided dietary data at S3 or S5. Outcomes were coronary heart disease (CHD), hypertension (HT), asthma, cancer (except skin cancer), diabetes mellitus (DM), depression and/or anxiety, and multimorbidity (MM). Longitudinal modelling using generalised estimation equation (GEE) approach with time-invariant (S4), time-varying (S4-S8) and lagged (S3-S7) covariates were performed. The mean (± standard deviation) of Alternative Healthy Eating Index-2010 (AHEI-2010) of participants (n = 8022) was 51·6 ± 11·0 (range: 19-91). Compared to women with the lowest DQ (AHEI-2010 quintile 1), those in quintile 5 had reduced odds of NCDs in time-invariant model (asthma: OR (95 % CI): 0·77 (0·62-0·96), time-varying model (HT: 0·71 (0·50-0·99); asthma: 0·62 (0·51-0·76); and MM: 0·75 (0·58-0·97) and lagged model (HT: 0·67 (0·49-0·91); and asthma: 0·70 (0·57-0·85). Temporal associations between diet and some NCDs were more prominent in lagged GEE analyses. Evidence of diet as NCD prevention in women aged 25-45 years is evolving, and more studies that consider different longitudinal analyses are needed.


Influence of procedural success on immediate and long-term clinical outcome of patients undergoing percutaneous revascularization of occluded coronary artery bypass vein grafts.
This study sought to determine whether successful recanalization of an occluded vein graft is associated with improvement in long-term clinical outcome. Coronary angioplasty of occluded vein grafts is associated with a lower initial success rate and a higher complication rate than angioplasty of vein grafts with subtotal stenoses and native coronary arteries. Whether successful angioplasty improves clinical outcome is unknown. We analyzed 77 consecutive patients who underwent angioplasty of an occluded saphenous vein coronary artery bypass graft between August 1983 and June 1994. Patients with a myocardial infarction in the previous 24 h were excluded from the study. The mean age of the study cohort was 65 years; the mean (+/- SD) age of the treated grafts was 7.5 +/- 3.9 years. As an adjunct to balloon angioplasty, stents were used in 9% of procedures, laser in 30%, and atherectomy in 16%, and thrombolytic therapy was administered in 23% of patients. The angioplasty success rate was 71%. Major complications within 30 days of the procedure included death in 5.2% of patients, Q wave myocardial infarction in 1.3% and repeat bypass surgery in 7.8%; these events occurred with similar frequency in patients in whom angiographic success was and was not achieved. Kaplan-meier analysis comparing patients in whom angioplasty was successful (n = 55) and not successful (n = 22) revealed no differences in survival or occurrence of myocardial infarction or recurrent severe angina between the two groups in the 3 years after the procedure. Univariate analysis identified the age of the graft and use of newer interventional devices as predictors of death or myocardial infarction during this time period; procedural success was not associated with freedom from these adverse events after adjusting for these variables. Angioplasty of occluded vein grafts is associated with a low initial success rate and a high complication rate. Successful angioplasty does not appear to reduce the occurrence of adverse events in the 3 years after the procedure.


The role of acetylcholinesterase in the pathogenesis of Alzheimer's disease.
Treatment of Alzheimer's disease has been dominated by the use of acetylcholinesterase (AChE) inhibitors. These drugs compensate for the death of cholinergic neurons and offer symptomatic relief by inhibiting acetylcholine (ACh) turnover and restoring synaptic levels of this neurotransmitter. Recently, however, AChE itself has been implicated in the pathogenesis of Alzheimer's disease. In particular, it appears that AChE may directly interact with amyloid-beta in a manner that increases the deposition of this peptide into insoluble plaques. This new role suggests that properly designed AChE inhibitors might be able to act as disease-modifying agents rather than as mere palliatives. Additionally, numerous studies have suggested that cholinergic modulation and other functional consequences of AChE inhibition may affect amyloid precursor protein processing and protect neurons against a variety of insults. It therefore seems likely that new AChE inhibitors, which capitalize on all these strengths would be excellent candidates for future Alzheimer's disease therapy.


Isometric Midthigh Pull Reliability and Relationship to Deadlift One Repetition Maximum.
De Witt, JK, English, KL, Crowell, JB, Kalogera, KL, Guilliams, ME, Nieschwitz, BE, Hanson, AM, and Ploutz-Snyder, LL. Isometric midthigh pull reliability and relationship to deadlift one repetition maximum. J Strength Cond Res 32(2): 528-533, 2018-The purpose of this investigation was to examine the reliability of the isometric midthigh pull (IMTP) and the relationship between IMTP peak force and deadlift 1 repetition maximum (1RM). Nine subjects (5 men and 4 women; 40.6 ± 8.0 years; 1.72 ± 0.10 m; 75.6 ± 13.4 kg) participated in this study. Isometric midthigh pull and deadlift 1RM were both performed during 2 testing sessions. For IMTP, peak force and peak rate of force development (RFD) were determined, in addition to RFD at 30 ms, 50 ms, 90 ms, 150 ms, 200 ms, and 250 ms after initiation of the pull. Intraclass correlation coefficients (ICCs) were calculated to evaluate the reliability of IMTP measures. Pearson product-moment correlations and linear regression were used to determine associations between IMTP and deadlift 1RM. Isometric midthigh pull peak force was reproducible both within (ICC = 0.98 and 0.97) and between sessions (ICC = 0.89) and significantly correlated with deadlift 1RM (r = 0.88, p ≤ 0.05), but intermediate force outputs and RFD were not. Lack of associations between RFD and deadlift 1RM indicate that the ability to create explosive force may be independent of the ability to create maximal force. The strong relationship between IMTP peak force and deadlift 1RM was present regardless of which IMTP repetition across the 2 sessions was examined. Peak force generated during IMTP is a reliable method to assess full body maximal strength. A single IMTP repetition, provided adequate familiarization and warm-up, correlates strongly with deadlift 1RM. Practitioners can use the IMTP test as a method to estimate maximal deadlift strength in a quick and potentially less provocative manner than traditional 1RM testing.


Measuring the association between marginalization and multimorbidity in Ontario, Canada: A cross-sectional study.
There is growing evidence to suggest that multimorbidity is not only a consequence of aging but also other environmental risk factors such as socio-economic status and social marginalization. In this study, the prevalence of multimorbidity was examined (defined as the simultaneous occurrence of two or more chronic morbidities) by age, gender and the Ontario Marginalization index (material deprivation, residential instability, dependency and ethnic concentration). With a cross-sectional design, 2015 data on 18 morbidities from 12,516,587 residents of the province of Ontario, Canada, were analysed. About 82.1% of the population had one or no chronic conditions, 10.3% were multimorbid with two chronic conditions and 7.6% had three or more chronic conditions. The results showed that the prevalence of multimorbidity is noticeably higher in the most deprived areas compared to least deprived for all age groups. Our findings challenge the notion that multimorbidity is primarily driven by aging. Of the 18% of the total population which were multimorbid, 43% of them were under the age of 65. We noted a substantial excess of multimorbidity in younger and middle-aged adults who were most deprived. In some cases, those in the most deprived areas were showing increased cases of multimorbidity nearly 10 years sooner than those who were least deprived. This study shows that environmental factors such as material deprivation and residential instability are correlated with higher prevalence of multimorbidity.


Comparison of the Proteome of Adult and Cord Erythroid Cells, and Changes in the Proteome Following Reticulocyte Maturation.
Cord blood stem cells are an attractive starting source for the production of red blood cells in vitro for therapy because of additional expansion potential compared with adult peripheral blood progenitors and cord blood banks usually being more representative of national populations than blood donors. Consequently, it is important to establish how similar cord RBCs are to adult cells. In this study, we used multiplex tandem mass tag labeling combined with nano-LC-MS/MS to compare the proteome of adult and cord RBCs and reticulocytes. 2838 unique proteins were identified, providing the most comprehensive compendium of RBC proteins to date. Using stringent criteria, 1674 proteins were quantified, and only a small number differed in amount between adult and cord RBC. We focused on proteins critical for RBC function. Of these, only the expected differences in globin subunits, along with higher levels of carbonic anhydrase 1 and 2 and aquaporin-1 in adult RBCs would be expected to have a phenotypic effect since they are associated with the differences in gaseous exchange between adults and neonates. Since the RBC and reticulocyte samples used were autologous, we catalogue the change in proteome following reticulocyte maturation. The majority of proteins (>60% of the 1671 quantified) reduced in abundance between 2- and 100-fold following maturation. However, ∼5% were at a higher level in RBCs, localized almost exclusively to cell membranes, in keeping with the known clearance of intracellular recycling pools during reticulocyte maturation. Overall, these data suggest that, with respect to the proteome, there is no barrier to the use of cord progenitors for the in vitro generation of RBCs for transfusion to adults other than the expression of fetal, not adult, hemoglobin.


Fractal organization of the pointwise correlation dimension of the heart rate.
To depict and quantify the degree of organization of the heart rate variability (HRV) in normal subjects. A modified algorithm was created to estimate series of 'point-dimensions' (PD2) from interbeat (R-R) interval series of 10 healthy subjects (21-56 years). Our innovation is twofold: (i) we quantified instances of low-dimensional chaos, random fluctuations, and those for which our method failed to provide either (due to poor statistics); (ii) consecutive subepochs of PD2s underwent a relative dispersion (RD) analysis, yielding an index (D) which quantifies the dynamical organization of the heart rate generator. The mean values of PD2 series varied between 4.58 and 5.88 (mean+/-SD= 5.21+/-0.41, n = 10). For group 1 (21-30 years, n = 6) we found an averaged PD2 of 5.49+/-0.27, while for group 2 (47-56 years, n = 4) PD2 averaged 4.79+/-0.17. The RD analysis performed for subepochs of PD2s yielded both instances obeying fractal scaling (D < 1.5) and stochasticity (D > 1.5). The average D for group 1 was 1.39+/-0.04 (14 subepochs) and for group 2, 1.20+/-0.008 (8 subepochs). Paired t-test and Hartley F-max test for comparison between D values and homogeneity of variance between the two groups were performed, yielding P-values 0.004 and 0.02, respectively. The complexity of the HRV seems to be modulated by a non-random fractal mechanism of a 'hyperchaotic' system, i.e. it can be hypothesized to contain more than one attractor. Also, our results support the 'chaos hypothesis' put forth recently, namely, the complexity of the cardiovascular dynamics is reduced with aging. The index of relative dispersion of the dimensional complexity has to be tested in various clinico-pathological settings, in order to corroborate its value as a potential new physiological measure.


Familial aggregation of age-related macular degeneration in the Utah population.
We examined familial aggregation and risk of age-related macular degeneration in the Utah population using a population-based case-control study. Over one million unique patient records were searched within the University of Utah Health Sciences Center and the Utah Population Database (UPDB), identifying 4764 patients with AMD. Specialized kinship analysis software was used to test for familial aggregation of disease, estimate the magnitude of familial risks, and identify families at high risk for disease. The population-attributable risk (PAR) for AMD was calculated to be 0.34. Recurrence risks in relatives indicate increased relative risks in siblings (2.95), first cousins (1.29), second cousins (1.13), and parents (5.66) of affected cases. There were 16 extended large families with AMD identified for potential use in genetic studies. Each family had five or more living affected members. The familial aggregation of AMD shown in this study exemplifies the merit of the UPDB and supports recent research demonstrating significant genetic contribution to disease development and progression.


Bridging translation for acute kidney injury with better preclinical modeling of human disease.
The current lack of effective therapeutics for patients with acute kidney injury (AKI) represents an important and unmet medical need. Given the importance of the clinical problem, it is time for us to take a few steps back and reexamine current practices. The focus of this review is to explore the extent to which failure of therapeutic translation from animal studies to human studies stems from deficiencies in the preclinical models of AKI. We will evaluate whether the preclinical models of AKI that are commonly used recapitulate the known pathophysiologies of AKI that are being modeled in humans, focusing on four common scenarios that are studied in clinical therapeutic intervention trials: cardiac surgery-induced AKI; contrast-induced AKI; cisplatin-induced AKI; and sepsis associated AKI. Based on our observations, we have identified a number of common limitations in current preclinical modeling of AKI that could be addressed. In the long term, we suggest that progress in developing better preclinical models of AKI will depend on developing a better understanding of human AKI. To this this end, we suggest that there is a need to develop greater in-depth molecular analyses of kidney biopsy tissues coupled with improved clinical and molecular classification of patients with AKI.


Biomarkers in Patients with Metastatic Breast Cancer and the PRAEGNANT Study Network.
Progress has been made in the treatment of metastatic breast cancer in recent decades, but very few therapies use patient or tumor-specific characteristics to tailor individualized treatment. More than ten years after the publication of the reference human genome sequence, analysis methods have improved enormously, fostering the hope that biomarkers can be used to individualize therapies and offer precise treatment based on tumor and patient characteristics. Biomarkers at every level of the system (genetics, epigenetics, gene expression, micro-RNA, proteomics and others) can be used for this. This has led to changes in clinical study designs, with drug developments often only focusing on small or very small subgroups of patients and tumors. The screening and registration of patients and their molecular tumor data has therefore become very important for the successful completion of clinical studies. This new form of medicine presents particular challenges for patients and physicians. Even in this new age of genome-wide analysis, the focus should still be on the patients' quality of life. This review summarizes recent developments and describes how the PRAEGNANT study network manages the aforementioned medical challenges and changes to create a professional infrastructure for patients and physicians.


Late complication of laparoscopic salpingoophorectomy: retained foreign body presenting as an acute abdomen.
Laparoscopy is widely used as a tool in many clinical situations allowing for diagnosis and/or surgical management in a minimally invasive fashion. Most laparoscopic cases are ambulatory and allow patients to recover quickly. Nonetheless, attention to surgical technique is paramount to avoid both short and long term complications. A 32-year-old woman had a laparoscopy and a reported left salpingoophorectomy for benign disease of the ovary in September, 1994. Shortly thereafter, in January, 1995, she was diagnosed with an intrauterine pregnancy and delivered in October of 1995 by spontaneous vaginal delivery. The pregnancy and delivery were both uncomplicated. The patient presented four weeks postpartum with clinical suspicion of appendicitis. However, at the time of laparotomy, the patient was found to have a retained foreign body from her prior laparoscopy in the right lower quadrant with a pelvic abscess and evidence of prior right salpingoophorectomy. The appendix appeared grossly normal. Laparoscopy is a safe, effective modality for various surgical and gynecologic conditions. Although laparoscopy is usually done on an outpatient basis, complications can manifest several weeks or months later. This case illustrates and reminds us of the importance of adherence to surgical laparoscopic principles. These include direct visualization when removing equipment and a complete count of surgical instrumentation to confirm the integrity of such at the end of each procedure.


False-positive CT gas cisternogram.
Nonfilling of the normal internal auditory canal on computed tomographic (CT) gas cisternography was observed in seven (11%) of 62 cases in a retrospective study of three series of gas cisternograms. The meatal surface of the fluid-filled canal was convex and pointed, simulating a small acoustic neuroma. A meniscus effect at the gas-cerebrospinal fluid interface was considered the probable cause of nonfilling of the canal with gas. Shaking the patient's head briskly after injection of gas into the spinal fluid will facilitate filling of the internal auditory canal with gas. Bone erosion in the canal or meatus suggests the presence of acoustic neuroma. In the absence of conclusive findings of neuroma, persistent nonfilling of the canal is an indication for repeat cisternography with an alternate contrast medium.


Histopathologic Evolution of Urothelial Carcinoma Recurrence in Transurethral Resection of the Urinary Bladder:35 Consecutive Cases And Literature Review
Background: Urothelial carcinoma (UC) is the malignancy most frequently encountered in the urinary bladder.The primary aim of this study was to make a reappraisal of histopathologic features, recurrence and progression. Materials and Methods: The records of cases consecutively diagnosed with UC in the state hospital pathology laboratory were collected. Cases were classified according to age, gender, histologic grade, pathologic staging [primary Tumor (pT)] ,tumor configuration, primary or recurrent status, and progression. Results: A total of 35 (29 male and 6 female) cases were examined. The mean age was 68.9 years with a male-to-female incidence ratio of 4.8:1. Low-grade UCs accounted for 20 (57.1%) and high-grade for 15 (42.9%). A papillary pattern was observed in 80% of the UCs, classified into the following pathological stages: 11 (31.4%) pTa, 22 (62.9%) pT1, and 2 (5.9%) pT2 cases. Eleven patients progressed to a higher stage (pT1 to pT2), and three cases from low to higher grade. We analyzed results for 26 (74.3%) cases aged 65 years or older. Conclusions: UCs have a great tendency for recurrence but potentially may be amenable to effective local or systemic treatments.


Is pulmonary function affected by bilateral dual transversus abdominis plane block? A randomized, placebo-controlled, double-blind, crossover pilot study in healthy male volunteers.
Transversus abdominis plane (TAP) blocks have been shown to reduce postoperative pain after various abdominal surgical procedures in several studies. The motor nerves of the abdominal wall are located in the same plane as the sensory nerves affected by the TAP block. The aim of this study was to examine whether the application of an ultrasound-guided TAP block would affect the muscles of the anterior abdominal wall with respect to their function as accessory respiratory muscles and hence pulmonary function. Twelve healthy male volunteers were included in a randomized, double-blind, crossover study. Primary outcome measure was change in forced expiratory volume in 1 sec (FEV1) after the bilateral dual injection of either 4 × 15 mL of 0.25% bupivacaine or saline. Secondary outcome measures included forced vital capacity, maximum expiratory pressure, and a number of frontal abdominal quadrants anesthetized. Change in FEV1 following the administration of bupivacaine showed a mean increase of 15 (SEM, 45.5) mL compared with the saline block, which showed a mean increase in FEV1 of 34 (SEM, 57.4) mL (P = 0.62). Similar results were obtained for forced vital capacity and maximum expiratory pressure. Abdominal quadrants were inconsistently anesthetized following administration of bupivacaine blocks. The administration of ultrasound-guided bilateral dual TAP blocks does not result in clinically relevant or statistically significant changes in the pulmonary function in healthy male subjects.


Enhanced attenuation of meningeal inflammation and brain edema by concomitant administration of anti-CD18 monoclonal antibodies and dexamethasone in experimental Haemophilus meningitis.
Antiinflammatory therapy has been shown to reduce the adverse pathophysiological consequences that occur in bacterial meningitis and to improve outcome from disease. In the present study, modulation of two principal steps of the meningeal inflammatory cascade was accomplished by concomitant administration of dexamethasone to diminish overproduction of cytokines in response to a bacterial stimulus and of a monoclonal antibody directed against adhesion-promoting receptors on leukocytes to inhibit recruitment of white blood cells into the subarachnoid space. Dexamethasone and antibody therapy produced a marked attenuation of all indices of meningeal inflammation and reduction of brain water accumulation after H. influenzae-induced meningitis in rabbits compared with results of each agent given alone and of untreated animals. In addition, the enhanced host's meningeal inflammatory reaction that follows antibiotic-induced bacterial lysis was profoundly ameliorated when dual therapy was administered without affecting clearance rates of bacteria from cerebrospinal fluid and vascular compartments. The combination of both therapeutic approaches may offer a promising mode of treatment to improve further the outcome from bacterial meningitis.


Unusual lysosomes in aortic smooth muscle cells: presence in living and rapidly frozen cells.
Unusual tubular structures have been observed in rat aortic smooth muscle cells (SMC) grown in culture. These tubular structures have several characteristics that strongly suggest that they are lysosomes: they are bounded by a single membrane bilayer, contain densely staining material, and acid phosphatase activity. Furthermore, these structures are present in living cells, as demonstrated by their ability to accumulate the membrane-impermeable fluorescent dye lucifer yellow CH. In ultrastructural preparations they are best seen in samples that are cryofixed by rapid freezing and then freeze-substituted in osmium-acetone solutions. Conventional chemical fixation did not appear to preserve these structures to as great an extent as did rapid freezing. Comparison of SMC in vitro to the same cells in situ revealed differences in lysosome number as well as morphological appearance. Thus, the culturing of rat SMC leads to the formation of unusual tubular lysosomes whose ultrastructural appearance is particularly sensitive to the methods employed for examination.


Policy Measures to Support Palliative Care at Home: A Cross-Country Case Comparison in Three European Countries.
The proportion of people in need of palliative care worldwide is rising, and the majority wish to receive this care at home. Many countries have created policy measures to support palliative care at home. To list and compare existing policy measures designed to support palliative care at home in addition to available primary care services in Belgium, France, and Germany. A cross-country case comparison based on expert consultation, governmental policy documents, and relevant scientific literature. All three countries have policy measures that allow informal caregivers to adapt their working patterns or take leave of absence to provide care without losing employee rights; however, only Belgium offers specific paid palliative care leave. All three countries offer various allowances to people who are dying at home and their caregivers. Cost-reductions for out-of-pocket expenses are available, based on the level of care dependency in Germany and on prognosis in Belgium, but are not provided in France. Mobile home support teams exist in all three countries and are free of charge for patients and caregivers; but only in Belgium and Germany, there are specialist multidisciplinary palliative home care teams. Belgium and Germany provide respite care for palliative patients. European countries with similar contextual characteristics offer comparable policy measures to support palliative care at home in addition to the available primary care services. However, important differences exist in the criteria for access and the extent of what is offered.


Overexpression of piRNA pathway genes in epithelial ovarian cancer.
The importance of the Piwi-interacting RNA (piRNA) pathway for germ cell maintenance, genome integrity, DNA methylation and retrotransposon control raises possible roles of this pathway in cancer. Indeed aberrant expression of human PIWI orthologs and Maelstrom has been observed in various cancers. In this study we explored the expression and function of piRNA pathway genes in human ovarian cancer, based on our recent work, which showed widespread expression of piRNA pathway genes in the mammalian. Our work shows that PIWIL1 and MAEL expression is significantly increased in malignant EOC (n = 25) compared to benign tumor tissues (n = 19) and normal ovarian tissue (n = 8). The expression of PIWIL3 is lower in malignant and benign tissues when compared to normal ovary. Sequencing of PIWIL1 transcript revealed that in many tumors deletion of exon 17 leads to the introduction of a premature stop codon in the PIWI domain, likely due to a splicing error. In situ hybridization on tumor sections revealed that L1, PIWIL1, 2 and MAEL are specifically expressed in epithelial cells (cancerous cells) of EOC. Furthermore, PIWIL2 and MAEL are co-expressed in the stromal cells adjacent to tumor cells. Since PIWIL1 and MAEL are up regulated in malignant EOC and expressed in the epithelial cells, we investigated if these two genes affect invasiveness of ovarian cancer cell lines that do not normally express these genes. PIWIL1 and MAEL were transiently over expressed in the ovarian cancer cell line SKOV3, followed by real-time measurements of cell invasiveness. Surprisingly both PIWIL1 and MAEL over expression decreased the invasiveness of SKOV3 cells. Our findings support a growing body of evidence that shows that genes in this pathway are upregulated in cancer. In ovarian cancer we show for the first time that Piwil1 transcript may often be abnormal result in non functional product. In contrast to what has been observed in other cell types, we found that PIWIL1 and MAEL have a repressive effect on cell invasiveness.


Immunocytochemical identification of proteins within the Pacinian corpuscle.
Light- and electron-microscopic immunocytochemistry (ICC) was performed on Pacinian corpuscles (PCs) obtained from cat mesentery to determine the presence and location of various proteins within the accessory capsule and the neurite. Antibodies to tubulin, neurofilament 200, actin, collagen II and V, glial fibrillary acidic protein (GFAP) and S-100 were used. Type II collagen was localized only in the outer core of the accessory capsule, which is composed of an inner core, an intermediate layer or growth zone, an outer core and an external capsule. Type V collagen was found only in the intermediate growth zone. Intermediate filaments labeled with anti-GFAP were only found in the inner core. The calcium-binding protein that was labeled by anti-S-100 was found only in the inner core. Diffuse and variable staining for actin is present throughout the accessory capsule. The differences in distribution of these various proteins within the capsule suggest different structural/functional properties of the various capsule regions. The neurite was found to contain microtubules (i.e., tubulin) and neurofilaments throughout, but these cellular inclusions were not found within the cytoplasmic extensions (filopodia) that project from the neurite into the hemilamellar clefts formed by the inner-core hemilamellae. The extensions, however, were found to contain actin in a much greater density than that seen in the neurite proper. The presence of actin, but apparent lack of other cytostructural elements within the extensions, is highly reminiscent of the composition of stereocilia found on vestibular and auditory hair cells. Since stereocilia have been shown to play a role in hair-cell mechanotransduction, it is possible that the cytoplasmic extensions are significantly involved with mechanotransduction within the PC.


Complement factor H is elevated in bronchoalveolar lavage fluid and sputum from patients with lung cancer.
Cytologic examination of specimens obtained from the respiratory tract is a lung cancer diagnostic procedure with high specificity but moderate sensitivity. The use of molecular biomarkers may enhance the sensitivity of cytologic examination in the detection of lung cancer. Complement factor H, a protein secreted by lung cancer cells, was quantified in a series of bronchoalveolar lavage supernatants from lung cancer patients and patients with nonmalignant respiratory diseases. Albumin, total protein content, and hemoglobin were also analyzed. Results were validated in independent sets of bronchoalveolar lavage and sputum supernatants. There was a significantly higher concentration of factor H in bronchoalveolar lavage samples from lung cancer patients. The sensitivity and specificity of the factor H test was 82% and 77%, respectively. These results were validated in an independent set of patients with nearly identical results. Furthermore, 70% and 45% of bronchoalveolar lavage fluids from central and peripheral tumors, respectively, reported as cytologically negative, were classified as positive using this marker. Finally, the test was evaluated in a series of sputum supernatants from lung cancer patients and controls. The sensitivity and specificity of the factor H test in this series was 80% and 88%, respectively. Factor H is elevated in bronchoalveolar lavage and sputum from lung cancer patients. Measurement of molecular biomarkers, such as complement factor H, may be used in the future as an adjunct to cytology in the diagnosis of malignant pulmonary diseases.


C6 produced by macrophages contributes to cardiac allograft rejection.
The terminal components of complement C5b-C9 can cause significant injury to cardiac allografts. Using C6-deficient rats, we have found that the rejection of major histocompatibility (MHC) class I-incompatible PVG.R8 (RT1.A(a)B(u)) cardiac allografts by PVG.1U (RT1.A(u)B(u)) recipients is particularly dependent on C6. This model was selected to determine whether tissue injury results from C6 produced by macrophages, which are a conspicuous component of infiltrates in rejecting transplants. We demonstrated that high levels of C6 mRNA are expressed in isolated populations of macrophages. The relevance of macrophage-produced C6 to cardiac allograft injury was investigated by transplanting hearts from PVG. R8 (C6-) donors to PVG.1U (C6-) rats which had been reconstituted with bone marrow from PVG.1U (C6+) rats as the sole source of C6. Hearts grafted to hosts after C6 reconstitution by bone marrow transplantation underwent rejection characterized by deposition of IgG and complement on the vascular endothelium together with extensive intravascular aggregates of P-selectin-positive platelets. At the time of acute rejection, the cardiac allografts contained extensive perivascular and interstitial macrophage infiltrates. RT-PCR and in situ hybridization demonstrated high levels of C6 mRNA in the macrophage-laden transplants. C6 protein levels were also increased in the circulation during rejection. To determine the relative contribution to cardiac allograft rejection of the low levels of circulating C6 produced systemically by macrophages, C6 containing serum was passively transferred to PVG.1U (C6-) recipients of PVG.R8 (C6-) hearts. This reconstituted the C6 levels to about 3 to 6% of normal values, but failed to induce allograft rejection. In control PVG.1U (C6-) recipients that were reconstituted with bone marrow from PVG.1U (C6-) donors, C6 levels remained undetectable and PVG.R8 cardiac allografts were not rejected. These results indicate that C6 produced by macrophages can cause significant tissue damage.


Reduced-Dose Deep Learning Reconstruction for Abdominal CT of Liver Metastases.
Background Assessment of liver lesions is constrained as CT radiation doses are lowered; evidence suggests deep learning reconstructions mitigate such effects. Purpose To evaluate liver metastases and image quality between reduced-dose deep learning image reconstruction (DLIR) and standard-dose filtered back projection (FBP) contrast-enhanced abdominal CT. Materials and Methods In this prospective Health Insurance Portability and Accountability Act-compliant study (September 2019 through April 2021), participants with biopsy-proven colorectal cancer and liver metastases at baseline CT underwent standard-dose and reduced-dose portal venous abdominal CT in the same breath hold. Three radiologists detected and characterized lesions at standard-dose FBP and reduced-dose DLIR, reported confidence, and scored image quality. Contrast-to-noise ratios for liver metastases were recorded. Summary statistics were reported, and a generalized linear mixed model was used. Results Fifty-one participants (mean age ± standard deviation, 57 years ± 13; 31 men) were evaluated. The mean volume CT dose index was 65.1% lower with reduced-dose CT (12.2 mGy) than with standard-dose CT (34.9 mGy). A total of 161 lesions (127 metastases, 34 benign lesions) with a mean size of 0.7 cm ± 0.3 were identified. Subjective image quality of reduced-dose DLIR was superior to that of standard-dose FBP (P < .001). The mean contrast-to-noise ratio for liver metastases of reduced-dose DLIR (3.9 ± 1.7) was higher than that of standard-dose FBP (3.5 ± 1.4) (P < .001). Differences in detection were identified only for lesions 0.5 cm or smaller: 63 of 65 lesions detected with standard-dose FBP (96.9%; 95% CI: 89.3, 99.6) and 47 lesions with reduced-dose DLIR (72.3%; 95% CI: 59.8, 82.7). Lesion accuracy with standard-dose FBP and reduced-dose DLIR was 80.1% (95% CI: 73.1, 86.0; 129 of 161 lesions) and 67.1% (95% CI: 59.3, 74.3; 108 of 161 lesions), respectively (P = .01). Lower lesion confidence was reported with a reduced dose (P < .001). Conclusion Deep learning image reconstruction (DLIR) improved CT image quality at 65% radiation dose reduction while preserving detection of liver lesions larger than 0.5 cm. Reduced-dose DLIR demonstrated overall inferior characterization of liver lesions and reader confidence. Clinical trial registration no. NCT03151564 © RSNA, 2022 Online supplemental material is available for this article.


Posterior fracture through the sternoclavicular physis associated with a clavicle fracture: a case report and literature review.
Three reported cases of fractures in teenagers of the medial clavicle associated with a posterior disruption at the sternoclavicular joint have similar findings. The medial fragment is rotated 90 degrees to the coronal plane. The medial fragment is usually stripped of its periosteum. Treatment requires open reduction and internal fixation of the clavicle fracture. We are reporting similar findings in a fourth case.


The effects of EGCG on fat oxidation and endurance performance in male cyclists.
Researchers have long been investigating strategies that can increase athletes' ability to oxidize fatty acids and spare carbohydrate, thus potentially improving endurance capacity. Green-tea extract (epigallocatechin-3-gallate; EGCG) has been shown to improve endurance capacity in mice. If a green-tea extract can stimulate fat oxidation and as a result spare glycogen stores, then athletes may benefit through improved endurance performance. Eight male cyclists completed a study incorporating a 3-way crossover, randomized, placebo-controlled, double-blinded, diet-controlled research design. All participants received 3 different treatments (placebo 270 mg, EGCG 270 mg, and placebo 270 mg + caffeine 3 mg/kg) over a 6-day period and 1 hr before exercise testing. Each participant completed 3 exercise trials consisting of 60 min of cycling at 60% maximum oxygen uptake (VO2(max)) immediately followed by a self-paced 40-km cycling time trial. The study found little benefit in consuming green-tea extract on fat oxidation or cycling performance, unlike caffeine, which did benefit cycling performance. The physiological responses observed during submaximal cycling after caffeine ingestion were similar to those reported previously, including an increase in heart rate (EGCG 147 +/- 17, caffeine 146 +/- 19, and placebo 144 +/- 15 beats/min), glucose at the 40-min exercise time point (placebo 5.0 +/- 0.8, EGCG 5.4 +/- 1.0, and caffeine 5.8 +/- 1.0 mmol/L), and resting plasma free fatty acids and no change in the amount of carbohydrate and fat being oxidized. Therefore, it was concluded that green-tea extract offers no additional benefit to cyclists over and above those achieved by using caffeine.


Preliminary evidence for reduced adipose tissue inflammation in vegetarians compared with omnivores.
There are links between obesity and inflammation that may relate activation of pro-inflammatory pathways by dietary factors. Because dietary fat intake of vegetarians is thought to be more beneficial than that of omnivores, we hypothesized that obese vegetarians would have less adipose tissue inflammation and lower intramyocellular ceramide concentrations than equally obese omnivores. Eight obese vegetarian (1 male) and 8 obese omnivore volunteers (1 male) completed a Food Frequency Questionnaire, underwent body composition measures, subcutaneous adipose tissue and muscle biopsies. We used immunohistochemistry to measure adipose macrophage (ATM) and senescent cells. Plasma free fatty acid (FFA), adipose FA and muscle ceramide profiles were measured using liquid chromatography/mass spectrometry. Student t tests were used for the comparison of primary outcomes; univariate regression analysis was used to test for associations between dietary patterns and ATMs (secondary analysis). There were no differences in age (38 ± 8 vs. 39 ± 8 years), BMI (32.2 ± 2.6 vs. 33.3 ± 1.9 kg/m2) or percent body fat (44 ± 8 vs. 45 ± 4) between the vegetarians and omnivores. Vegetarians consumed 42% (P = 0.02) less saturated fat and 50% (P = 0.04) less cholesterol than the omnivores. Plasma FFA of vegetarians had lesser proportions of palmitic acid (24 ± 3 vs. 29 ± 4%, P = 0.02) and vegetarians had fewer femoral pro-inflammatory ATMs than omnivores (3.6 ± 2.8 vs. 7.9 ± 4.4 per 100 adipocytes, respectively; P = 0.02). Omnivores had 50% greater (P = 0.01) expression of TNF mRNA in abdominal fat. We found no significant between group differences in muscle ceramide concentrations. Although the sample size is small, these results may indicate that dietary patterns play a role in adipose tissue inflammation, as reflected by reduced number of femoral ATMs in obese vegetarians than obese omnivores.


[Structure of the internal capsid of rotaviruses].
Several methodical approaches (negative staining, filtration by rotation, modeling, optic diffraction, and filtration of images) were used to study the structure of ther internal capsid of rotavirus and the structure and mutual arrangement of capsomers comprising it. The internal capsid of rotaviruses was shown to be constructed as a skew icosadeltahedron (left) with T-13 and to consist of 12 pentamers and 120 hexamers. The structural units (a total of 780) comprising capsomers are organized into trimers, each trimer participating in the formation of three adjacent capsomers, while each of the structural units is a part of only one capsomer.


Essential thrombocythemia: Rare cause of chorea.
Essential thrombocythemia (ET) is a clonal myeloproliferative disorder (MPD), characterized predominantly by a markedly elevated platelet count without known cause. It is rare hematological disorder. In ET clinical picture is dominated by a predisposition to vascular occlusive events and hemorrhages. Headache, transient ischemic attack, stroke, visual disturbances and light headedness are some of the neurological manifestations of ET. Here, we describe a 55 year-old female who presented to us with generalized chorea. On evaluation, she was found to have thrombocytosis. After ruling out the secondary causes of thrombocytosis and other MPD we confirmed diagnosis of ET in her by bone marrow studies. Polycythemia vera (PV) another MPD closely related to ET may be present with generalized chorea. There are few case reports of PV presenting as chorea in the literature, but none with ET. We report the first case of ET presenting as generalized chorea.


[Role of substance P in regulating the feeding behavior and the avoidance reaction in the rabbit].
Similar changes in feeding and avoidance reaction in spite of the way of substance P administration (30 mgk/kg intravenously or 14,8 nmol intraventricular) were found in rabbits with electrodes implanted in various limbic-midbrain structures. Feeding was found to be more sensitive to substance P administration, as it was shown by the decrease of excitability of the hypothalamic "feeding center" and abolishing of the inhibitory and facilitatory effects on this center from the dorsal hippocampus and the midbrain reticular formation, correspondingly. New cortical-subcortical integration under substance P was presented in new characteristics of EEG activity in neocortical areas, both background and in response to stimulation of various limbic-midbrain structures. Biochemical data let to suggest that at the neural level substance P led to destabilization of membrane structures in endoplasmatic reticulum and to redistribution of membrane-connected N-acetylneuramine acid which was directly involved in neurotransmission.


[Binding of bile salts and lysolecithin by various antacids in biological media].
The in vitro capacity of several commercial antacids to bind bile acids and lysolecithin was measured in three different test media: 0.1 n HCl, natural human gastric juice and human gastric juice enriched with 5% protein. Antacids bind bile salts variably. In HCl and in natural and protein-enriched gastric juice the capacity to bind conjugated bile salts was higher (47-72%) for antacids with high aluminium content, such as Alucol, Andursil, Muthesa than for antacids with less aluminium such as Calamox and Riopan (17-18%). Binding of unconjugated bile salts did not show any corresponding difference. The test medium had little effect on binding capacity when pH was comparable. Natural gastric juice was slightly better with regard to binding of conjugated bile salts. The addition of protein had only minimal effect. Lysolecithin was equally heavily adsorbed by all tested antacids and in all three test conditions (85-100%). Since duodenogastral reflux contains mainly unconjugated bile salts, our results suggest that antacids with higher aluminium content should be preferred if binding of bile salt reflux is attempted.


Rho-Associated Protein Kinase (ROCK) Promotes Proliferation and Migration of PC-3 and DU145 Prostate Cancer Cells by Targeting LIM Kinase 1 (LIMK1) and Matrix Metalloproteinase-2 (MMP-2).
BACKGROUND In the pathogenesis and progression of prostate cancer, cell proliferation and cell migration results in tumor invasion and metastasis that is associated with patient morbidity and mortality. Rho-associated protein kinase (ROCK) has previously been shown to be upregulated in prostate cancer, but its biological role remains poorly understood. This study aimed to investigate the role of ROCK in the proliferation and migration of PC-3 and DU145 prostate cancer cells and to identify the possible targets involved by knockdown of ROCK1 and ROCK2 RNA expression. MATERIAL AND METHODS An RNA interference (RNAi) assay was performed to silence the expression of ROCK1 and ROCK2 in the PC-3 and DU145 human prostate cancer cell lines. Cells were also treated with a specific ROCK inhibitor, Y27632. A cell counting kit-8 (CCK-8) assay was used to determine the proliferation rate of prostate cancer cells, and cell migration and invasion assays were performed. Western blot and polymerase chain reaction were used to measure protein and RNA expression levels. RESULTS In PC-3 and DU145 prostate cancer cells, knockdown of ROCK1 and ROCK2 reduced cell migration and invasion. ROCK1 and ROCK2 regulated cell proliferation in PC-3 and DU145 prostate cancer cells. Protein levels of phosphorylated LIM kinase 1 (p-LIMK1) and matrix metalloproteinase-2 (MMP-2) were reduced in ROCK1 and ROCK2 siRNA transfected cells. CONCLUSIONS In PC-3 and DU145 human prostate cancer cells, ROCK promoted cell proliferation and migration by targeting LIMK1 and MMP-2.


Biological functions of UDP-glucose synthesis in Streptococcus mutans.
A gene encoding glucose-1-phosphate uridylyltransferase (EC 18.104.22.168) was isolated from Streptococcus mutans. A cell extract of Escherichia coli expressing the cloned gene exhibited glucose-1-phosphate uridylyltransferase activity. The enzyme catalyses the conversion of D-glucose 1-phosphate and UTP into UDP-D-glucose. Rabbit antiserum against the serotype-c-specific antigen did not react with autoclaved extracts from mutant cells in which the cloned gene was insertionally inactivated. The glucose content of the cell-wall preparation purified from the mutant was very much lowered, whereas there was no observable decrease in the content of rhamnose. When the mutant strain was grown in an acidic environment, its cell viability was much lower than that of the wild-type. These results suggest that UDP-D-glucose functions not only as an immediate precursor of the serotype-c-specific antigen of S. mutans (as a glucose donor for side-chain formation), but is also important for the organism's viability in environmental conditions of low pH.


Polaron pair mediated triplet generation in polymer/fullerene blends.
Electron spin is a key consideration for the function of organic semiconductors in light-emitting diodes and solar cells, as well as spintronic applications relying on organic magnetoresistance. A mechanism for triplet excited state generation in such systems is by recombination of electron-hole pairs. However, the exact charge recombination mechanism, whether geminate or nongeminate and whether it involves spin-state mixing is not well understood. In this work, the dynamics of free charge separation competing with recombination to polymer triplet states is studied in two closely related polymer-fullerene blends with differing polymer fluorination and photovoltaic performance. Using time-resolved laser spectroscopic techniques and quantum chemical calculations, we show that lower charge separation in the fluorinated system is associated with the formation of bound electron-hole pairs, which undergo spin-state mixing on the nanosecond timescale and subsequent geminate recombination to triplet excitons. We find that these bound electron-hole pairs can be dissociated by electric fields.


Quantitative pharmacological analysis of 2-125I-iodomelatonin binding sites in discrete areas of the chicken brain.
We have localized and characterized 2-125I-iodomelatonin binding sites in the chicken brain using in vitro quantitative autoradiography. Binding sites were widely distributed throughout the chicken brain, predominantly in regions associated with the visual system. The specific binding of 2-125I-iodomelatonin to discrete chicken brain areas was found to be saturable, reversible, and of high affinity. The specific binding of 2-125I-iodomelatonin (75 pm) was quantitated for 40 identifiable brain regions. Eight brain regions were chosen for binding characterization and pharmacological analysis: optic tectum, Edinger-Westphal nucleus, oculomotor nucleus, nucleus rotundus, ventral supraoptic decussation, ventrolateral geniculate nucleus, neostriatum, and ectostriatum. These regions showed no rostral-caudal gradient in 2-125I-iodomelatonin specific binding, and saturation analysis revealed a single class of high-affinity sites with KD values in the range of 33-48 pM and receptor site density (Bmax) ranging from 31 to 58 fmol/mg protein. Competition experiments carried out with various indoles revealed a similar order of pharmacological affinities in these areas: melatonin greater than 6-chloromelatonin greater than methoxyluzindole greater than N-acetylserotonin greater than luzindole much greater than 5-HT greater than 5-methoxytryptamine. The affinity constants determined by quantitative autoradiography for these compounds to compete for 2-125I-iodomelatonin binding in the optic tectum correlated well with the affinities in chicken brain membranes at 25 degrees C (r = 0.966; slope = 0.845; n = 7) and 0 degree C (r = 0.946; slope = 0.379; n = 7), chicken retinal membranes (r = 0.973; slope = 0.759; n = 7), and the potency or affinity of these compounds to affect the calcium-dependent release of 3H-dopamine from the rabbit retina (r = 0.902; slope = 0.506; n = 6). We conclude that the high-affinity sites labeled by 2-125I-iodomelatonin in various chicken brain areas have identical binding and pharmacological characteristics to the ML-1 melatonin binding site previously described in chicken brain and retinal membranes and to the ML-1 melatonin receptor modulating dopamine release from the retina. In the chicken brain, the ML-1 receptor site may mediate functional responses regulated by melatonin.


Quantitative separation of polystyrene nanoparticles in environmental matrices with picogram detection limits using capillary electrophoresis.
We developed a capillary electrophoresis method to separate polystyrene particles (PSPs) with different sizes or different surface functionalities. Separations were performed in buffer and 100 mg L-1 clay or 100 mg L-1 Suwanee River humic acid. In all solutions, PSPs were baseline or near-baseline resolved in less than 15 minutes.


The reliability of digitized radiographs for dental identification: a Web-based study.
In the era of Daubert and other judicial rulings pertaining to the acceptability of forensic evidence, it is increasingly important that experts are able to testify that their methods have been scientifically tested and that error rates and other factors relating to reliability have been published. The purpose of this study was to determine the reliability of digitized radiographic comparisons for the purposes of dental identification. Participants with various forensic backgrounds and experience levels were passively recruited to the website. Ten forensic identification cases composed of antemortem and postmortem dental radiographs were supplied to examiners using a bespoke website. Participants responded to the cases on two occasions after a one-month washout interval using the ABFO conclusion levels for forensic identifications. A total of 115 first attempts and 87 matched second attempts were received. Of the total responses, 72% were dentally trained respondents who had completed at least one forensic identification case; of these, 38% were experienced forensic dentists who had completed more than 25 identifications. Data relating to accuracy, intra- and inter-examiner agreement, and the effect of case difficulty are presented. Mean accuracy was 85.5% for all cases, with the experienced forensic dentists obtaining a 91% success rate. The inter-examiner agreement on the negative identification cases was classified as poor. The data suggest that dental identifications resulting from the comparison of postmortem and antemortem radiographs are valid, accurate, and reliable when undertaken by experienced odontologists.


Predictors of emotional distress after stroke.
The aim of this prospective longitudinal study was to identify factors relating to emotional distress in the first 6 months after stroke in a sample including patients with aphasia. One hundred patients who were in hospital at 1 month after stroke were recruited and assessed on measures of communication impairment (Sheffield Screening Test), personal activities of daily living (Barthel Index), and emotional distress (Visual Analogue Self-Esteem Scale). Demographic and stroke characteristics were recorded. Patients (n=92) were reassessed on the same measures 6 months after stroke, in addition to assessing extended activities of daily living (Nottingham Extended Activities of Daily Living Scale). Patients were aged 44 to 86 years (51 men), and 21 were classified as having aphasia. Multiple linear regression showed that expressive communication impairment and dependence in personal activities of daily living were significant predictors of emotional distress at 1 month after stroke (R(2)=24%). Expressive communication impairment, emotional distress at 1 month after stroke, and having a more severe stroke were significant predictors of emotional distress at 6 months after stroke (R(2)=55%). Distress levels were similar at 1 month and 6 months after stroke. Demographic characteristics and side of lesion were unrelated to distress. Expressive communication impairment and level of disability in personal activities of daily living were related to distress. Distress was persistent in the first 6 months after stroke. Appropriate treatment strategies need to be developed and evaluated for patients who have communication impairments.


Suppression of fragmentation in multiphoton ionization mass spectrometry using a near-infrared femtosecond laser as an ionization source.
The ionization and fragmentation processes for pentachlorobenzene were examined using a femtosecond laser emitting at 400, 800, and 1200 nm. A molecular ion was clearly observed in the mass spectrum, since the molecule can be directly ionized from the singlet electronic exited state before relaxation to triplet levels, because the pulse width of the laser is shorter than the lifetime of the excited state. Fragmentation was minimal at 1200 nm, in contrast to ionization at 800 and 400 nm. Indeed, a doubly-charged molecular ion was prominent at 800 nm, owing to the absorption band of the singly-charged molecular ion at this wavelength. Fragmentation was further enhanced at 400 nm, which can be explained by the dissociation of the doubly-charged molecular ion having a larger absorption band at 400 nm. Fragmentation was strongly affected by the absorption character of the ionic species, i.e., singly- and doubly-charged molecular ions, appeared in the process of multiphoton ionization.


[Usefulness of PSA-complex in the diagnosis of prostatic carcinoma].
Since its discovery as a marker for prostate cancer, there have been many attempts to enhance the diagnostic efficacy of the prostate specific antigen (PSA). Among these are the studies that analyze the behavior of different forms of serum PSA bound to different antiproteases, such as alpha-1-antichymotrypsin, which forms the complexed PSA (PSA-c). This study analyzed the utility of PSA-c to enhance specificity without altering sensitivity in comparison to total PSA (PSA-t). From September 1998 to March 1999, blood samples were obtained from 96 patients that had undergone a prostate biopsy due to a suspicion of prostate cancer. PSA-c, PSA-t (Technicon Immunol system, Bayer) and PSA-c/PSA-t ratio were analyzed in these patients. ROC curves were plotted and the optimal cutoffs were found for which the specificity was higher for PSA-c (44.6% [CI 95%, 32-57]) versus PSA-t (35.4% [CI 95%, 25-49]) and the PSA-c/PSA-t ratio (38.5% [CI 95%, 27-51]) while maintaining a similar sensitivity index (90%). PSA-c showed similar results for other values of sensitivity. PSA-c was found to improve specificity in comparison to PSA-t and PSA-c/PSA-t ratio. PSA-c determination could avoid unnecessary biopsies without altering sensitivity; i.e., the same number of prostate cancers will be detected.


Associations between subcutaneous fat density and systemic inflammation differ by HIV serostatus and are independent of fat quantity.
Adipose tissue (AT) density measurement may provide information about AT quality among people living with HIV. We assessed AT density and evaluated relationships between AT density and immunometabolic biomarker concentrations in men with HIV. Cross-sectional analysis of men enrolled in the Multicenter AIDS Cohort Study. Abdominal visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) density (Hounsfield units, HU; less negative = more dense) were quantified from computed tomography (CT) scans. Multivariate linear regression models described relationships between abdominal AT density and circulating biomarker concentrations. HIV+ men had denser SAT (-95 vs -98 HU HIV-, P < 0.001), whereas VAT density was equivalent by HIV serostatus men (382 HIV-, 462 HIV+). Historical thymidine analog nucleoside reverse transcriptase inhibitor (tNRTI) use was associated with denser SAT but not VAT. In adjusted models, a 1 s.d. greater SAT or VAT density was associated with higher levels of adiponectin, leptin, HOMA-IR and triglyceride:HDL cholesterol ratio and lower hs-CRP concentrations in HIV- men. Conversely, in HIV+ men, each s.d. greater SAT density was not associated with metabolic parameter improvements and was significantly (P < 0.05) associated with higher systemic inflammation. Trends toward higher inflammatory biomarker concentrations per 1 s.d. greater VAT density were also observed among HIV+ men. Among men living with HIV, greater SAT density was associated with greater systemic inflammation independent of SAT area. AT density measurement provides additional insight into AT density beyond measurement of AT quantity alone, and may have implications for metabolic disease risk.


A curriculum on care for people with disabilities: effects on medical student self-reported attitudes and comfort level.
Early, frequent encounters with people with disabilities may improve medical students' knowledge, attitudes and skills regarding their care. We developed and implemented a longitudinal four-year curriculum addressing caring for people with disabilities. To test differences in mean scores between intervention and control groups on individual post-survey items regarding attitudes toward people with disabilities, and to conduct exploratory procedures to examine individual factors that may account for group differences. Students at two U.S. medical schools, one with the new curriculum, and one with no specific disabilities curriculum, were surveyed in Year 1 of medical school, prior to curriculum introduction, and again at the end of Year 3, using a validated 30-item instrument measuring medical students' self-reported attitudes and comfort toward people with disabilities. We compared mean item ratings between the two groups using χ(2) and ANOVA. Principal components analysis was then used to construct linear composite variables that were then regressed on potential predictors of attitudes and comfort level. The intervention led to significant or near-significant improvement in several factors. However, male students in the intervention group, particularly those who encountered people with disabilities in a clinical context, had a tendency to more frequently agree with negative statements (β = .628, p = .005). Exposure of medical students to a longitudinal curriculum for caring for people with disabilities led to significant improvement in several factors related to comfort and attitudes. The gender-related reinforcement of some negative attitudes merits further investigation and caution when implementing the curriculum in the future.