Excreted urinary mediators in an animal model of experimental immune nephritis with potential pathogenic significance.
Currently, proteinuria is viewed as the earliest indicator of renal disease in immune-mediated nephritis. The objective of this study was to determine whether additional mediators may be excreted in the urine during immune-mediated nephritis, using an experimental model with a well-defined disease course. Urine samples from mice with anti-glomerular basement membrane (anti-GBM) antibody-induced experimental nephritis were screened using a focused immunoproteome array bearing 62 cytokines/chemokines/soluble receptors. Molecules identified through this screening assay were validated using an enzyme-linked immunosorbent assay. One of these molecules was further evaluated for its pathogenic role in disease, using antibody-blocking studies. Compared with B6 and BALB/c mice, in which moderately severe immune-mediated nephritis develops, the highly nephritis-susceptible 129/Sv and DBA/1 mice exhibited significantly increased urinary levels of vascular cell adhesion molecule 1 (VCAM-1), P-selectin, tumor necrosis factor receptor I (TNFRI), and CXCL16, particularly at the peak of disease. Whereas some of the mediators appeared to be serum derived early in the disease course, local production in the kidneys appeared to be an important source of these mediators later in the course of disease. Both intrinsic renal cells and infiltrating leukocytes appeared to be capable of producing these mediators. Finally, antibody-mediated blocking of CXCL16 ameliorated experimental immune nephritis. These studies identified VCAM-1, P-selectin, TNFRI, and CXCL16 as a quartet of molecules that have potential pathogenic significance; the levels of these molecules are significantly elevated during experimental immune nephritis. The relevance of these molecules in spontaneous immune nephritis warrants investigation.


Pandemic Pedagogy: Perception of Nursing students': A cross-sectional study.
Coronavirus disease 2019 pandemic impacted across the globe disrupting all sectors including the higher education universities. Nursing institutions faced various challenges due to the pandemic restrictions, of which the abrupt shift of implementing the curriculum to online mode posed a major challenge to both the teachers and the students. To assess nursing students' perception of pandemic pedagogy and the challenges faced in online teaching-learning, this cross-sectional survey was conducted among 982 undergraduate nursing students from three Deemed to be University nursing institutions of Southern India. Institutional Ethics Committee approval (IEC 444/2020), permission from the heads of the institutions and study participant's consent was obtained. Data was collected using an online survey questionnaire which had three domains, including student-related (19 items), teacher-related(5 items), and physical learning environment-related factors (11 items). The reliability was established using Cronbach's Alpha (0.86). Explored the favouring, hindering factors and challenges faced during the emergency remote teaching with open-ended items. The overall mean score of perceptions on pandemic pedagogy was 89.03±10.03. Sixty-three percent of students had a total perception score above 87 which indicates that they preferred online learning during the pandemic whereas 45% preferred classroom learning. There was a significant difference in the total perception scores and the years of study( F (3, 978) = 4.96, p = 0.002). The factors favouring online learning were, an opportunity to view the recorded classes even after the live classes' (n=165), and 'more time to spend for learning activities' (n=152). Factors that hindered the learning or the challenges faced were poor network connectivity (n=451), and lack of opportunity for group study (n=326). Students favoured online learning during the pandemic; however, there were several challenges. The educational institutions need to prepare themselves to overcome this and focus on a blended learning curriculum.


Parasitic plants have increased rates of molecular evolution across all three genomes.
Theoretical models and experimental evidence suggest that rates of molecular evolution could be raised in parasitic organisms compared to non-parasitic taxa. Parasitic plants provide an ideal test for these predictions, as there are at least a dozen independent origins of the parasitic lifestyle in angiosperms. Studies of a number of parasitic plant lineages have suggested faster rates of molecular evolution, but the results of some studies have been mixed. Comparative analysis of all parasitic plant lineages, including sequences from all three genomes, is needed to examine the generality of the relationship between rates of molecular evolution and parasitism in plants. We analysed DNA sequence data from the mitochondrial, nuclear and chloroplast genomes for 12 independent evolutionary origins of parasitism in angiosperms. We demonstrated that parasitic lineages have a faster rate of molecular evolution than their non-parasitic relatives in sequences for all three genomes, for both synonymous and nonsynonymous substitutions. Our results prove that raised rates of molecular evolution are a general feature of parasitic plants, not confined to a few taxa or specific genes. We discuss possible causes for this relationship, including increased positive selection associated with host-parasite arms races, relaxed selection, reduced population size or repeated bottlenecks, increased mutation rates, and indirect causal links with generation time and body size. We find no evidence that faster rates are due to smaller effective populations sizes or changes in selection pressure. Instead, our results suggest that parasitic plants have a higher mutation rate than their close non-parasitic relatives. This may be due to a direct connection, where some aspect of the parasitic lifestyle drives the evolution of raised mutation rates. Alternatively, this pattern may be driven by an indirect connection between rates and parasitism: for example, parasitic plants tend to be smaller than their non-parasitic relatives, which may result in more cell generations per year, thus a higher rate of mutations arising from DNA copy errors per unit time. Demonstration that adoption of a parasitic lifestyle influences the rate of genomic evolution is relevant to attempts to infer molecular phylogenies of parasitic plants and to estimate their evolutionary divergence times using sequence data.


Comparison of gastric lesions in dogs and cats with and without gastric spiral organisms.
To determine prevalence of gastric spiral organisms (GSO) in dogs and cats that were clinically normal or had primary gastrointestinal disease and to compare histologic lesions of the stomach in dogs and cats with and without GSO. 21 dogs and 10 cats that were clinically normal and 56 dogs and 33 cats with gastrointestinal disease. Case-control study. Unevenness of the gastric mucosal surface was detected, using endoscopic techniques in 20 and 25% of clinically normal and abnormal dogs, respectively. On histologic examination, GSO were located on the mucosal surface within or beneath the mucus, in gastric pits, and within glandular lumina in 86 and 90% of clinically normal dogs and cats, respectively, and in 61 and 64% of clinically abnormal dogs and cats, respectively. Prevalence of GSO infection in dogs and cats that were clinically abnormal was not higher than in those that were clinically normal. Infection was detected in stomachs of > 60% of dogs and cats 1 year old or less. Helicobacter pylori was not isolated from any specimen; however, specimens in which GSO were found had positive results on a urease test. Prevalence of GSO infection was high in clinically normal and abnormal dogs and cats, some of which were young. This should be considered during assessment of clinically normal animals with GSO as they can be a potential reservoir for infection in human beings.


Vitamin C depletion is associated with alterations in blood histamine and plasma free carnitine in adults.
The purpose of this study was to determine whether carnitine metabolism or histamine degradation would be useful parameters for investigating the optimal requirement for vitamin C. Twenty-two non-scorbutic subjects with subnormal vitamin C status (plasma vitamin C < 28 mumol/L) were placed on a metabolic diet low in vitamin C for 3 weeks and repleted with graded doses of vitamin C: 10, 30 and 60 mg vitamin C daily (group 1) or 10,125 and 250 mg vitamin C daily (group 2) for weeks 1, 2 and 3, respectively. Fasting blood samples were collected weekly and analyzed for plasma vitamin C, plasma free carnitine and blood histamine. Group 1 subjects remained in a subnormal vitamin C state throughout the 3-week study, and blood histamine and plasma free carnitine were not impacted by the experimental treatment. Plasma vitamin C in group 2 subjects rose significantly during the study, and these subjects finished the study with an ample vitamin C status indicative of vitamin C intakes above the recommended dietary allowance. Both blood histamine and plasma free carnitine were inversely related to vitamin C status in group 2 subjects. These data indicate that blood histamine and plasma free carnitine are altered in individuals with subnormal, non-scorbutic vitamin C status and provide evidence that metabolic changes independent of collagen metabolism occur prior to the manifestation of scurvy. Thus utilizing scurvy as an end-point to determine vitamin C requirements may not provide adequate vitamin C to promote optimal health and well-being.


A systematic literature review on the use and outcomes of maternal and child healthcare services by undocumented migrants in Europe.
Undocumented migrants, in particular pregnant women and their newborns, constitute a particularly vulnerable group of migrants. The aim of this study was to systematically review the academic literature on the use and outcomes of maternal and child healthcare by undocumented migrants in the European Union (EU) and European Free Trade Association (EFTA) countries. The databases, MEDLINE, Embase, CINAHL Plus, Global Health and Popline were searched for the period 2007 to 2017. Two independent reviewers judged the eligibility of studies. The final number of included studies was 33. The results of quantitative, qualitative and mixed methods studies were analysed separately due to their differences in study design, sample size and quality. Overall, the quantitative studies found that undocumented women underutilised essential maternal and child healthcare services, and experienced worse health outcomes. Qualitative studies supported these results, indicating that undocumented migrants were hesitant to use services due to a lack of knowledge and fear of deportation. Studies included in the review covered 10 of 32 EU or EFTA countries, making a European comparison impossible. Despite major methodological differences between included studies, the results of this review indicate that the status of undocumented migrants exacerbates known health risks and hampers service use.


Evaluation of cytokines for expansion of the megakaryocyte and granulocyte lineages.
The goal of our study was to identify cytokine combinations that would result in simultaneous ex vivo expansion of both the megakaryocyte (Mk) and granulocyte lineages, since these cell types have the potential to reduce the periods of thrombocytopenia and neutropenia following chemotherapy. We investigated the effects of cytokine combinations on expansion of the Mk (CD41a+ cells and colony forming unit [CFU]-Mk) and granulocyte (CD15+ cells and CFU-granulocyte/monocyte [GM]) lineages. Peripheral blood CD34+ cells were cultured in serum-free medium with interleukin 3 (IL-3), stem cell factor (SCF), and various combinations of thrombopoietin (TPO), IL-6, GM-CSF, and/or G-CSF. The Mk lineage was primarily influenced by TPO in our cultures, although Mk and CFU-Mk numbers were increased when TPO was combined with IL-6. The primary stimulator of the granulocyte lineage was G-CSF, although many synergistic and additive effects were observed with addition of other factors. Expansion of CFU-GM increased upon addition of more cytokines. The cytokine combination of IL-3, SCF, TPO, IL-6, GM-CSF and G-CSF produced the greatest number of granulocytes and CFU-GM. The minimum cytokines necessary for expansion of both the Mk and granulocyte lineages included TPO and G-CSF, since no other factors examined could increase Mk and granulocyte numbers to the same extent. The number of hematopoietic progenitors produced in our culture system should be sufficient for successful engraftment following myelosuppressive therapy if produced on a scale of about one liter.


Smoking before isometric exercise amplifies myocardial stress and dysregulates baroreceptor sensitivity and cerebral oxygenation.
This crossover study examined whether acute cardiovascular responses, baroreceptor sensitivity (BRS), and brain oxygenation during isometric exercise are altered after cigarette smoking. Twelve young, habitual smokers randomly performed a smoking and a control protocol, during which participants smoked one cigarette (0.9 mg nicotine) or a sham cigarette, before exercise. Testing involved baseline, a 5-minute smoking, a 10-minute post-smoking rest, 3-minute handgrip exercise (30% maximum voluntary contraction), and recovery. Beat-to-beat blood pressure, heart rate (HR), and cerebral oxygenation (near infrared spectroscopy) were continuously monitored. Double-product, stroke volume (SV), cardiac output, systemic vascular resistance and BRS were assessed. During post-smoking rest, systolic or diastolic blood pressure (140.8 ± 12.1/87.0 ± 6.9 vs. 125.9 ± 7.1/77.3 ± 5.5 mm Hg), HR, and double product were higher in the smoking versus the control protocol, whereas BRS was lower (P < .05). During handgrip exercise, smoking resulted in greater HR and double product (17,240 ± 3893 vs. 15,424 ± 3173 mm Hg·bpm) and lower BRS versus the control protocol (P < .05), without significant differences in stroke volume and systemic vascular resistance between protocols. During recovery, smoking elicited a delayed return of brain oxygenation indices, lower BRS, and higher double product. Smoking a cigarette shortly before the exercise session amplifies myocardial stress and dysregulates autonomic function and cerebral oxygenation during exercise and recovery, even in young habitual smokers, perceived as free from long-term cardiovascular effects of smoking.


Cost-effectiveness of two long-lasting insecticidal nets delivery models in mass campaign in rural Mozambique.
The aim is to compare the cost-effectiveness of two long-lasting insecticidal nets (LLINs) delivery models (standard vs. new) in universal coverage (UC) campaigns in rural Mozambique. The total financial cost of delivering LLINs was US$ 231,237.30 and US$ 174,790.14 in the intervention (302,648 LLINs were delivered) and control districts (219,613 LLINs were delivered), respectively. The average cost-effectiveness ratio (ACER) per LLIN delivered and ACER per household (HH) achieving UC was lower in the intervention districts. The incremental cost-effectiveness ratio (ICER) per LLIN and ICER per HH reaching UC were US$ 0.68 and US$ 2.24, respectively. Both incremental net benefit (for delivered LLIN and for HHs reaching UC) were positive (intervention deemed cost-effective). Overall, the newer delivery model was the more cost-effective intervention. However, the long-term sustainability of either delivery models is far from guaranteed in Mozambique's current economic context.


Alpha-keto and alpha-hydroxy branched-chain acid interrelationships in normal humans.
Plasma concentrations of the branched-chain amino acids leucine, isoleucine and valine, and those of leucine's and isoleucine's transamination products alpha-ketoisocaproic acid (KICA) and alpha-keto-beta-methylvaleric acid (KMVA), respectively, are known to increase after a protein meal or during extended fasting, but little or no increase in the concentration of valine's transamination product, alpha-ketoisovaleric acid (KIVA), has been observed under these conditions. To determine whether this could be explained by the conversion of KIVA to its alpha-hydroxy analogue, we measured the plasma concentrations of KICA, KMVA and KIVA, as well as their alpha-hydroxy analogues [alpha-hydroxyisocaproic acid (HICA), alpha-hydroxy-beta-methylvaleric acid (HMVA) and alpha-hydroxyisovaleric acid (HIVA)], in normal volunteers immediately after a protein meal or during a 60-h fast. We also determined the oxidoreduction equilibrium constants for HIVA/KIVA and HICA/KICA and their extent of plasma protein binding. In subjects in the postabsorptive state, the plasma concentrations of KICA and KMVA were 100 times those of HICA and HMVA, whereas that of KIVA was only twice that of HIVA. Shortly after a protein meal, KICA and KMVA concentrations increased significantly by 30 and 60%, respectively, whereas that of KIVA decreased by 25% (P < 0.05). HICA, HMVA and HIVA concentrations did not change. During prolonged fasting the plasma concentrations of all six metabolites increased gradually. The high plasma keto/hydroxy acid ratios were not related to their K(eq), which favored alpha-hydroxy analogue formation. The reduction of the branched-chain alpha-keto acids to their alpha-hydroxy analogues seems to take place too slowly to attain thermodynamic equilibrium.(ABSTRACT TRUNCATED AT 250 WORDS)


[Complications following orbital floor fractures].
Complications after orbital floor fractures were studied in 76 cases (follow-up time 4 years). The following procedures were performed by the maxillofacial surgeon: repositioning of the orbital floor, tamponade of the maxillary sinus, covering of the defect with Lyodura, autologous bone grafting, and balloon catheterization. A satisfactory result was achieved after the primary operation in 75% of the cases. In cooperation with the ophthalmologist a variety of complications in 19 patients were studied and analyzed. The results of this study show the necessity of diagnostic and surgical cooperation between the specialists concerned.


Platinum drugs and DNA repair mechanisms in lung cancer.
The standard first-line treatment for around 80% of newly-diagnosed advanced non-small cell lung cancer (NSCLC) is chemotherapy. Currently, patients are allocated to chemotherapy on the basis of clinical conditions, comorbidities and histology. If feasible, platinum-based chemotherapy is considered as the most efficacious option. Due to the heterogeneity in terms of platinum-sensitivity among patients with NSCLC, great efforts have been made in order to identify molecular predictive markers of platinum resistance. Based on the mechanism of action of platinum, several components of DNA repair pathways have been investigated as potential predictive markers. The main DNA repair pathways involved in the repair of platinum-induced DNA damage are nucleotide excision repair and homologous recombination. The most studied potential predictive markers of platinum-sensitivity are Excision Repair Cross Complementing-1 (ERCC1) and Brest Cancer Type-I Susceptibility protein (BRCA1); however, increasing biological knowledge about DNA repair pathways suggests the potential clinical usefulness of integrated analysis of multiple DNA repair components.


The interplay between density- and trait-mediated effects in predator-prey interactions: a case study in aphid wing polymorphism.
Natural enemies not only influence prey density but they can also cause the modification of traits in their victims. While such non-lethal effects can be very important for the dynamic and structure of prey populations, little is known about their interaction with the density-mediated effects of natural enemies. We investigated the relationship between predation rate, prey density and trait modification in two aphid-aphid predator interactions. Pea aphids (Acyrthosiphon pisum, Harris) have been shown to produce winged dispersal morphs in response to the presence of ladybirds or parasitoid natural enemies. This trait modification influences the ability of aphids to disperse and to colonise new habitats, and hence has a bearing on the population dynamics of the prey. In two experiments we examined wing induction in pea aphids as a function of the rate of predation when hoverfly larvae (Episyrphus balteatus) and lacewing larvae (Chrysoperla carnea) were allowed to forage in pea aphid colonies. Both hoverfly and lacewing larvae caused a significant increase in the percentage of winged morphs among offspring compared to control treatments, emphasising that wing induction in the presence of natural enemies is a general response in pea aphids. The percentage of winged offspring was, however, dependent on the rate of predation, with a small effect of predation on aphid wing induction at very high and very low predation rates, and a strong response of aphids at medium predation rates. Aphid wing induction was influenced by the interplay between predation rate and the resultant prey density. Our results suggests that density-mediated and trait-mediated effects of natural enemies are closely connected to each other and jointly determine the effect of natural enemies on prey population dynamics.


IDLat: An Importance-Driven Latent Generation Method for Scientific Data.
Deep learning based latent representations have been widely used for numerous scientific visualization applications such as isosurface similarity analysis, volume rendering, flow field synthesis, and data reduction, just to name a few. However, existing latent representations are mostly generated from raw data in an unsupervised manner, which makes it difficult to incorporate domain interest to control the size of the latent representations and the quality of the reconstructed data. In this paper, we present a novel importance-driven latent representation to facilitate domain-interest-guided scientific data visualization and analysis. We utilize spatial importance maps to represent various scientific interests and take them as the input to a feature transformation network to guide latent generation. We further reduced the latent size by a lossless entropy encoding algorithm trained together with the autoencoder, improving the storage and memory efficiency. We qualitatively and quantitatively evaluate the effectiveness and efficiency of latent representations generated by our method with data from multiple scientific visualization applications.


Lack of mucosal involvement in pemphigus foliaceus may be due to low expression of desmoglein 1.
Oral mucosal lesions are seen in most cases of pemphigus vulgaris, whereas they are only rarely seen in pemphigus foliaceus; however, both pemphigus vulgaris and pemphigus foliaceus sera show positive immunofluorescence staining on oral mucosa. To explain this apparent paradox, we examined the expression level of desmoglein (Dsg)3, pemphigus vulgaris antigen, and Dsg1, pemphigus foliaceus antigen, in human squamous mucosal epithelia and epidermis by immunofluorescence staining and immunoblotting. For immunofluorescence staining, Dsg isotype-specific antibodies were produced by immunoadsorbing pemphigus vulgaris sera with either recombinant Dsg1 or Dsg3 baculoprotein. In oral mucosa and esophagus both Dsg were immunoreactive on cell surfaces throughout the entire epithelia, but staining intensity was weaker for Dsg1 than for Dsg3. Immunoblotting was performed to compare Dsg1 and Dsg3 expression levels in extracts from epidermis and oral mucosa. The total amount of desmosomal proteins applied was adjusted to give the same degree of staining intensity for desmoplakin, a cytoplasmic plaque protein of desmosomes. In the mucosal extract, the Dsg1 band was much weaker than Dsg3, whereas in the epidermal extract the Dsg1 band was stronger than Dsg3. These data suggest that although Dsg1 and Dsg3 are expressed in a similar distribution throughout squamous mucosal epithelia, Dsg1 is expressed at a much lower level than Dsg3. This finding provides a good explanation for the paradox: even though anti-Dsg1 autoantibodies block the function of Dsg1 in the mucosal epithelia, Dsg3 may be sufficient for cell-cell adhesion, with consequently no apparent oral involvement in pemphigus foliaceus patients.


Forces between functionalized silica nanoparticles in solution.
To prevent the flocculation and phase separation of nanoparticles in solution, nanoparticles are often functionalized with short chain surfactants. Here we present fully atomistic molecular dynamics simulations which characterize how these functional coatings affect the interactions between nanoparticles and with the surrounding solvent. For 5-nm-diameter silica nanoparticles coated with poly(ethylene oxide) (PEO) oligomers in water, we determined the hydrodynamic drag on two approaching nanoparticles moving through solvent and on a single nanoparticle as it approaches a planar surface. In most circumstances, macroscale fluid theory accurately predicts the drag on these nanoscale particles. Good agreement is seen with Brenner's analytical solutions for wall separations larger than the soft nanoparticle radius. For two approaching coated nanoparticles, the solvent-mediated (velocity independent) and lubrication (velocity-dependent) forces are purely repulsive and do not exhibit force oscillations that are typical of uncoated rigid spheres.


[Electroconvulsive therapy for multiple major self-mutilations in bipolar psychotic depression].
Self-mutilation is form of self-injurious behavior which is either low intensity, high frequency form seen in personality disorder and mental retardation or low frequency, highly destructive form which occurs in the context of psychosis or acute intoxications. We report a 32 yr-old male with bipolar affective disorder presenting with multiple acts of major self-mutilation during an episode of psychotic depression. At presentation he had broken upper central incisors, circular burn scar on right palm, crush injury of left index finger with avulsed nail and cut injury over glans penis. In view of his extreme self-mutilating behavior, he was administered electroconvulsive therapy on second day following which self-mutilating behavior improved after fourth ECT. After 8 ECT sessions, he was started on lithium carbonate with a serum level of 0.82 meq/L and haloperidol 15 mg/day and there was no recurrence of self-mutilating behavior during follow up after four months.


Spontaneous rib fractures in a black woman with familial hypocalciuric hypercalcemia.
Familial hypocalciuric hypercalcemia (FHH) is a rare but important consideration in the differential diagnosis of hypercalcemia. FHH results from an autosomal dominantly inherited inactivating mutation of the calcium sensing receptor (CaSR) gene and is typically associated with a benign clinical course and normal bone mineral density. We describe the unusual case of a 57-year old African American woman with spontaneous rib fractures who was found to have FHH due to a novel set of polymorphisms of the CaSR gene. She also had hypertension, esophageal reflux disease treated with proton pump inhibitors, osteopenia by DEXA scanning, and a prior left ankle fracture in the absence of significant trauma. There was no suggestive family history and her only sibling had a normal serum calcium. The patient was evaluated extensively for potential causes of osteoporotic fractures. It is imperative to screen for FHH using 24-hour urinary calcium and creatinine excretion in subjects with hypercalcemia irrespective of ethnicity and a history of non-traumatic rib fractures. This approach may prevent unnecessary neck exploration for parathyroidectomy which is unwarranted in FHH.


Psychological Effects of Skin Incision Size in Minimally Invasive Valve Surgery Patients.
Clinical benefits of minimally invasive cardiac valve surgery (MIVS) have been reported. Improved postoperative mental status was never analyzed with dedicated psychological tests. In the present study we intend to investigate potential benefits of MIVS for patient psychological well-being, with special attention to the relevance of the patient perception of the chest surgical scar, of the self body image and cosmetic aspects. Between 2016 and 2017, 87 eligible patients, age 66.5 ± 14.5 years, operated on for heart valve surgery, underwent either conventional full sternotomy (CS; n = 48) or MIVS by V-shape hemi-sternotomy approach (n = 39). Before selection of the surgical approach, patients had undergone preoperative evaluation of their psychological status using Beck Depression Inventory-II (BDI-II), State-Trait Anxiety Inventory Form Y (STAI-Y), and EuroQol-5D (EQ-5D) psychological tests. Six months postoperatively, patients filled in dedicated questionnaires to assess their psychological status, quality of life, and subjective perception, thus repeating the above-mentioned tests and adding the Body Image Questionnaire (BIQ) and Patient and Observer Scar Assessment Scale (POSAS) v2.0 tests for scar-healing process evaluation. No patient died during the study.The 4 post-test scales of psychological well-being (BDI-II P = 0.04, STAI-Y P = 0.04, 2 indices of EQ-5D P = 0.03, P = 0.01) showed significant differences between the MIVS group and CS group, with MIVS-small incision patients having lower level of depression and anxiety symptoms and better quality of life. Mean score differences of scar perception (BIQ and POSAS v2.0) were significant, with MIVS patients having evaluated the scar quality significantly better than CS patients. MIVS appears associated with significant esthetical and related psychological benefits, as documented by technical tests. These findings should be considered when selecting the most appropriate technique for heart valve surgery.


Biosensor-based approach to the identification of protein kinase ligands with dual-site modes of action.
The authors have used a surface plasmon resonance (SPR)-based biosensor approach to identify and characterize compounds with a unique binding mode to protein kinases. Biacore was used to characterize hits from an enzymatic high-throughput screen of the Tec family tyrosine kinase, IL2-inducible T cell kinase (ITK). Complex binding kinetics was observed for some compounds, which led to identification of compounds that bound simultaneously at both the adenosine triphosphate (ATP) binding site and a second, allosteric site on ITK. The presence of the second binding site was confirmed by X-ray crystallography. The second site is located in the N-terminal lobe of the protein kinase catalytic domain, adjacent to but distinct from the ATP site. To enable rapid optimization of binding properties, a competition-based Biacore assay has been developed to successfully identify second site noncompetitive binders that have been confirmed by X-ray crystallographic studies. The authors have found that SPR technology is a key method for rapid identification of compounds with dual-site modes of action.


Comparison of comorbidity indices for patients with head and neck cancer.
Comorbidity is an important prognostic factor for elderly patients with head and neck cancer. Investigators are faced with the dilemma of selecting the appropriate comorbidity instrument for outcomes research in cancer. The goal of this study was to compare 2 general comorbidity indices with 2 disease-specific indices. The Surveillance, Epidemiology, and End Results (SEER)-Medicare-linked database was used to identify 15,493 patients with incident squamous cell carcinomas of the oral cavity, pharynx, and larynx first diagnosed between December 1983 and December 1994. Comorbid ailments were identified through the use of the International Classification of Diseases, 9th edition codes in the Medicare inpatient and outpatient claims for 7131 patients. The overall severity of comorbidity was classified according to 2 general comorbidity indices: the Charlson Comorbidity Index and the Klabunde Index, and 2 disease-specific indices: the Washington University Head and Neck Index and the Head and Neck Cancer Index. Overall survival was the primary end point. Cox proportional hazards analysis was used to assess the performance and discrimination of the comorbidity indices. For each of the 4 comorbidity indices, there was a weak trend of worse survival with higher levels of comorbidity. The 2 general indices performed as well as the 2 disease-specific indices and no instrument clearly performed better than the others. Both the general and disease-specific comorbidity indices provided important prognostic information. The disease-specific indices did not perform better than the general indices. In this claims-based analysis, there was no apparent advantage to using a disease-specific index when attempting to predict overall survival.


Dynamic membrane topology of the Escherichia coli beta-glucoside transporter BglF.
The Escherichia coli BglF protein, a permease of the phosphoenolpyruvate-dependent phosphotransferase system, catalyzes transport and phosphorylation of beta-glucosides. In addition, BglF regulates bgl operon expression by controlling the activity of the transcriptional regulator BglG via reversible phosphorylation. BglF is composed of three domains; one is hydrophobic, which presumably forms the sugar translocation channel. We studied the topology of this domain by Cys-replacement mutagenesis and chemical modification by thiol reagents. Most Cys substitutions were well tolerated, as demonstrated by the ability of the mutant proteins to catalyze BglF activities. Our results suggest that the membrane domain contains eight transmembrane helices and an alleged cytoplasmic loop that contains two additional helices. The latter region forms a dynamic structure, as evidenced by the alternation of residues near its ends between faced-in and faced-out states. We suggest that this region, together with the two transmembrane helices encompassing it, forms the sugar translocation channel. BglF periplasmic loops are close to the membrane, the first being a reentrant loop. This is the first systematic topological study carried out with an intact phosphotransferase system permease and the first demonstration of a reentrant loop in this group of proteins.


Reduced autonomic responses to faces in Capgras delusion.
People experiencing the Capgras delusion claim that others, usually those quite close emotionally, have been replaced by near-identical impostors. Ellis & Young suggested in 1990 that the Capgras delusion results from damage to a neurological system involved in orienting responses to seen faces based on their personal significance. This hypothesis predicts that people suffering the Capgras delusion will be hyporesponsive to familiar faces. We tested this prediction in five people with Capgras delusion. Comparison data were obtained from five middle-aged members of the general public, and a psychiatric control group of five patients taking similar anti-psychotic medication. Capgras delusion patients did not reveal autonomic discrimination between familiar and unfamiliar faces, but orienting responses to auditory tones were normal in magnitude and rate of initial habituation, showing that the hyporesponsiveness is circumscribed.


An improved outdoor calibration procedure for broadband ultraviolet radiometers.
This article aims at improving the broadband ultraviolet radiometer's calibration methodology. For this goal, three broadband radiometers are calibrated against a spectrophotometer of reference. Three different one-step calibration models are tested: ratio, first order and second order. The latter is proposed in order to adequately reproduce the high dependence on the solar zenith angle shown by the other two models and, therefore, to improve the calibration performance at high solar elevations. The proposed new second-order model requires no additional information and, thus, keeps the operational character of the one-step methodology. The models are compared in terms of their root mean square error and the most qualified is subsequently validated by comparing its predictions with the spectrophotometer measurements within an independent validation data subset. Results show that the best calibration is achieved by the second-order model, with a mean bias error and mean absolute bias error lower than 2.2 and 6.7%, respectively.


Phylogeographic insights into the invasion history and secondary spread of the signal crayfish in Japan.
Successful invasion by nonindigenous species is often attributed to high propagule pressure, yet some foreign species become widespread despite showing reduced genetic variation due to founder effects. The signal crayfish (Pacifastacus leniusculus) is one such example, where rapid spread across Japan in recent decades is believed to be the result of only three founding populations. To infer the history and explore the success of this remarkable crayfish invasion, we combined detailed phylogeographical and morphological analyses conducted in both the introduced and native ranges. We sequenced 16S mitochondrial DNA of signal crayfish from across the introduced range in Japan (537 samples, 20 sites) and the native range in western North America (700 samples, 50 sites). Because chela size is often related to aggressive behavior in crayfish, and hence, their invasion success, we also measured chela size of a subset of specimens in both introduced and native ranges. Genetic diversity of introduced signal crayfish populations was as high as that of the dominant phylogeographic group in the native range, suggesting high propagule pressure during invasion. More recently established crayfish populations in Japan that originated through secondary spread from one of the founding populations exhibit reduced genetic diversity relative to older populations, probably as a result of founder effects. However, these newer populations also show larger chela size, consistent with expectations of rapid adaptations or phenotypic responses during the invasion process. Introduced signal crayfish populations in Japan originate from multiple source populations from a wide geographic range in the native range of western North America. A combination of high genetic diversity, especially for older populations in the invasive range, and rapid adaptation to colonization, manifested as larger chela in recent invasions, likely contribute to invasion success of signal crayfish in Japan.


Long term effects of epoetin alfa in patients with ST- elevation myocardial infarction.
The HEBE III trial showed that epoetin alfa administration in patients with a first ST-elevation myocardial infarction (STEMI) did not improve left ventricular function at 6 weeks after primary percutaneous coronary intervention (PCI). The long term effects of erythropoiesis- stimulating agents on cardiovascular morbidity and mortality are unknown, therefore we evaluated clinical events at 1 year after PCI. A total of 529 patients with a first STEMI and successful primary PCI were randomized to standard optimal medical treatment (N = 266) or an additional bolus of 60,000 IU epoetin alfa administered intravenously (N = 263) within 3 h after PCI. Analyses were performed by intention to treat. At 1 year after STEMI, 485 patients had complete follow-up. The rate of the composite end point of all-cause mortality, re-infarction, target vessel revascularization, stroke and/or heart failure was 6.4 % (N = 15) in the epoetin alfa group and 9.6 % (N = 24) in the control group (p = 0.18). Thromboembolic events were present in 1.3 % (N = 3) of patients in the epoetin alfa group and 2.4 % (N = 6) in the control group. There was no evidence of benefit from epoetin alfa administration in subgroups of patients. Administration of a single bolus of epoetin alfa in patients with STEMI does not result in a reduction of cardiovascular events at 1 year after primary PCI. There was a comparable incidence of thromboembolic complications in both treatment groups, suggesting that epoetin alfa administration is safe at long term.


A double mass extinction at the end of the paleozoic era.
Three tests based on fossil data indicate that high rates of extinction recorded in the penultimate (Guadalupian) stage of the Paleozoic era are not artifacts of a poor fossil record. Instead, they represent an abrupt mass extinction that was one of the largest to occur in the past half billion years. The final mass extinction of the era, which took place about 5 million years after the Guadalupian event, remains the most severe biotic crisis of all time. Taxonomic losses in the Late Permian were partitioned among the two crises and the intervening interval, however, and the terminal Permian crisis eliminated only about 80 percent of marine species, not 95 or 96 percent as earlier estimates have suggested.


Multiclass relevance vector machines: sparsity and accuracy.
In this paper, we investigate the sparsity and recognition capabilities of two approximate Bayesian classification algorithms, the multiclass multi-kernel relevance vector machines (mRVMs) that have been recently proposed. We provide an insight into the behavior of the mRVM models by performing a wide experimentation on a large range of real-world datasets. Furthermore, we monitor various model fitting characteristics that identify the predictive nature of the proposed methods and compare against existing classification techniques. By introducing novel convergence measures, sample selection strategies and model improvements, it is demonstrated that mRVMs can produce state-of-the-art results on multiclass discrimination problems. In addition, this is achieved by utilizing only a very small fraction of the available observation data.


Club drug users had higher odds of reporting a bacterial STI compared with non-club drug users: results from a cross-sectional analysis of gay and bisexual men on HIV pre-exposure prophylaxis.
Pre-exposure prophylaxis (PrEP) can reduce HIV transmission risk for many gay, bisexual and other men who have sex with men. However, bacterial STI (BSTI) associated with decreasing condom use among HIV PrEP users is a growing concern. Determining the characteristics of current PrEP users at highest BSTI risk fills a critical gap in the literature. Gay and bisexual men (GBM) in New York City on HIV PrEP for 6 or more months (n=65) were asked about chlamydia, gonorrhoea and syphilis diagnoses in the past 6 months. By design, half (51%) of the sample were club drug users. We examined the associations of length of time on PrEP, type of PrEP care provider, PrEP adherence, number of sexual partners, number of condomless anal sex acts and club drug use on self-reported BSTI using multivariable, binary logistic regressions, adjusting for age, race/ethnicity, education and income. Twenty-six per cent of GBM on HIV PrEP reported a diagnosis of BSTI in the past 6 months. Men who reported club drug use (adjusted OR (AOR)=6.60, p<0.05) and more frequent condomless anal sex in the past 30 days (AOR=1.13, p<0.05) had higher odds of reporting a BSTI. No other variables were significantly associated with self-reported BSTI in the multivariable models. Club drug users could be at a unique BSTI risk, perhaps because of higher risk sexual networks. Findings should be considered preliminary, but suggest the importance of ongoing BSTI screening and risk-reduction counselling for GBM on HIV PrEP.


Long intergenic noncoding RNA p21 mediates oxidized LDL‑induced apoptosis and expression of LOX‑1 in human coronary artery endothelial cells.
Atherosclerosis is the most common pathological cause of cardiovascular diseases, and endothelial dysfunction has a vital role. It has been suggested that inhibiting endothelial cell apoptosis induced by oxidized low‑density lipoprotein (ox‑LDL), an essential atherosclerotic factor, is a potential novel therapeutic strategy against atherosclerosis. Previous studies have revealed that endothelial lectin‑like ox‑LDL receptor‑1 (LOX‑1) and long intergenic noncoding RNA p21 (lincRNA‑p21) may serve as therapeutic targets for atherosclerosis and associated cardiovascular disorders. The present study investigated the role of lincRNA‑p21 in oxLDL‑induced apoptosis and expression of LOX‑1 in human coronary artery endothelial cells (HCAECs). Primary HCAECs were treated with ox‑LDL (30, 60 or 90 µg/ml) for 24 or 48 h, and the expression of lincRNA‑p21, LOX‑1 and cell apoptosis rate were measured. Ox‑LDL dose‑ and time‑dependently induced the expression of lincRNA‑p21 and LOX‑1 and apoptosis in HCAECs. Lentiviral overexpression of lincRNA‑p21 markedly increased oxLDL‑induced apoptosis and the expression of LOX‑1 in HCAECs. Additionally, the effect was largely blocked by selective protein kinase C (PKC) inhibitor, rottlerin. However, lentiviral knockdown of lincRNA‑p21 markedly decreased oxLDL‑induced apoptosis and the expression of LOX‑1. In addition, overexpression and knockdown of lincRNA‑p21 markedly increased and decreased oxLDL‑induced PKCδ activity/phosphorylation, respectively. In conclusion, to the best of our knowledge, the present study provides the first evidence indicating that lincRNA‑p21 is a major mediator of oxLDL‑induced apoptosis and expression of LOX‑1 in human vascular endothelial cells, and acts via activation of PKCδ. These results provide insights into the role of lincRNA‑p21 in the pathogenesis of atherosclerosis.


Pulmonary hemodynamic and tidal volume changes during exercise in heart failure.
Impairment of lung mechanics, increase of pulmonary artery pressure and limitation of exercise capacity are common findings in chronic heart failure. The objective of the present study was to evaluate whether pulmonary mechanics are correlated with pulmonary hemodynamics, whether both are correlated with the functional capacity and whether the time course of their changes during exercise correlates with the exercise capacity. We performed a cardiopulmonary exercise test (breath by breath analysis of ventilation and gas exchange, cycloergometer, 25 W increments every 3 min) with pulmonary hemodynamic monitoring in 38 heart failure patients. The parameters were analyzed at rest, 1 min after the work rate increase and at peak exercise. A significant linear correlation with peak oxygen consumption was found at rest for: mean pulmonary artery pressure (mPAP, r = -0.56), right atrial pressure (RAP, r = -0.42), pulmonary wedge pressure (PWP, r = -0.53), and total pulmonary (TPR, r = -0.53) and pulmonary vascular resistances (PVR, r = -0.45); after 1 min of exercise for: cardiac index (CI, r = 0.49), mPAP (r = -0.57), RAP (r = -0.60), PWP (r = -0.45), and TPR (r = -0.67) and PVR (r = -0.38); at peak exercise for: tidal volume (r = 0.63), CI (r = 0.63), RAP (r = -0.43), TPR (r = -0.65) and PVR (r = -0.43). A significant linear correlation with peak oxygen consumption was found, for the increment between rest and 1 min of exercise, for RAP (r = -0.58) and CI (r = 0.42) and, for the increments between rest and peak exercise, for tidal volume (r = 0.79) and CI (r = 0.61) and, for the ratio between the increment between rest and 1 min of exercise/increment between rest and peak exercise, for mPAP (r = -0.42), RAP (r = 0.51) and CI (r = -0.54). The same ratio of increment of mPAP (r = 0.39) and CI (r = 0.36) correlated with that of tidal volume. This study provides evidence of a strong correlation between the respiratory function and pulmonary vascular pressure changes during exercise in heart failure.


Visuokinesthetic perception of hand movement is mediated by cerebro-cerebellar interaction between the left cerebellum and right parietal cortex.
Combination of visual and kinesthetic information is essential to perceive bodily movements. We conducted behavioral and functional magnetic resonance imaging experiments to investigate the neuronal correlates of visuokinesthetic combination in perception of hand movement. Participants experienced illusory flexion movement of their hand elicited by tendon vibration while they viewed video-recorded flexion (congruent: CONG) or extension (incongruent: INCONG) motions of their hand. The amount of illusory experience was graded by the visual velocities only when visual information regarding hand motion was concordant with kinesthetic information (CONG). The left posterolateral cerebellum was specifically recruited under the CONG, and this left cerebellar activation was consistent for both left and right hands. The left cerebellar activity reflected the participants' intensity of illusory hand movement under the CONG, and we further showed that coupling of activity between the left cerebellum and the "right" parietal cortex emerges during this visuokinesthetic combination/perception. The "left" cerebellum, working with the anatomically connected high-order bodily region of the "right" parietal cortex, participates in online combination of exteroceptive (vision) and interoceptive (kinesthesia) information to perceive hand movement. The cerebro-cerebellar interaction may underlie updating of one's "body image," when perceiving bodily movement from visual and kinesthetic information.


Gender vulnerabilities, spousal abuse and the incidence of HIV in Lesotho:a case for an integrative rights-based approach.
The article posits that imbalances in gender relations are influencing two distinctive yet connected crises for women in Lesotho: the HIV epidemic and spousal abuse. The overarching premise is that as spousal abuse is increasingly recognised and as HIV infections spread, responses to the phenomenon do not reflect the related risks and consequences in married women's lives. This article underscores the nexus of connections between HIV and spousal abuse in Lesotho, identifying potential areas for pragmatic state-led responses. Applying a rights-based approach, it assesses women's vulnerability to each problem at the individual, societal and programmatic levels, noting that there are both direct and underlying factors heightening risks for women. The article asks, what is the value added by a rights-based approach to the subject under discourse? And, how can a rights-based approach be translated into practical tools for planning, monitoring and evaluating projects and programmes aimed at tackling the multifaceted risks and challenges of HIV and spousal abuse confronting women in Lesotho? In response to these questions, the author identifies three trajectories of opportunities for an integrated, comprehensive response. The unmistakable anchor of the article's propositions is the rights-based approach. Although the discussion focuses on Lesotho, the implications for the broader African region cannot be overemphasised in light of commonly shared experiences pertaining to the severe difficulties posed by spousal abuse and HIV.


Chemotherapeutic evaluation of Celecoxib, a cyclooxygenase-2 inhibitor, in a rat mammary tumor model.
Epidemiological and experimental studies have shown that non-steroidal anti-inflammatory drugs (NSAIDs) reduce the relative risk of human cancer, including breast cancer. Recently, research studies in our laboratories have shown that the selective cyclooxygenase-2 (COX-2) blocker, Celecoxib, given daily in the diet, significantly inhibited the induction of rat mammary tumors by 7, 12-dimethylbenz(a)anthracene (DMBA). These studies were extended to evaluate Celecoxib for its effectiveness as an antineoplastic agent in this rat mammary tumor model. We examined the growth inhibitory effects of Celecoxib, given daily in the diet, on the volume and the number of established mammary tumors, vis-a-vis the cancer load (CL). Tumors continued to grow actively in control rats fed chow diet only. In contrast, the Celecoxib-supplemented diet (1500 mg/kg diet) significantly decreased the size of the mammary tumors in rats over the 6 week treatment period, resulting in an average reduction in tumor volume of approximately 32%, relative to the baseline volume (p<0.04). At the end of the 6 week treatment period, average tumor volume was 1.45 cm3 and 0.13 cm3 in the control and Celecoxib treated rats respectively. Tumor regression occurred in 90% of the rats. In addition, new tumors continued to emerge in the control group, in contrast to their significantly decreasing numbers in the Celecoxib treated group over the same time period (p<0.05). These results indicate that Celecoxib has significant antineoplastic activity, in addition to its anticarcinogenic effects.


New monitoring technique with an ICA algorithm in the wastewater treatment process.
A new monitoring method using independent component analysis (ICA) is suggested for the wastewater treatment process (WWTP). ICA is an extension of PCA (Principal Component Analysis). While PCA can only impose independence up to the second order (mean and variance) with constraint on the direction vectors to be orthogonal, ICA imposes statistical independence up to more than second order on the individual component and has no orthogonal condition. When the variables have the Gaussian distribution, PCA itself provides a satisfactory result in monitoring performance. However, the measured variables are not often normally distributed. In this case, ICA can provide better monitoring results than PCA since ICA is based on the assumption that the latent variables are not normally distributed. In this paper, the ICA monitoring algorithm with kernel density estimation was applied to fault detection and diagnosis of the wastewater simulation benchmark. ICA with kernel density estimation gives better results than PCA in disturbance detection in spite of severe periodic features of the wastewater plant.


Predictive factors for early neurological deterioration after intravenous thrombolysis of single subcortical infarction in the territory of the middle cerebral artery.
Patients with a single subcortical infarction (SSI) in the territory of the middle cerebral artery (MCA) often experience early neurological deterioration (END) despite receiving intravenous thrombolytic therapy (IVT). In this study, predictors of END were investigated in patients with SSI in the MCA after IVT. Patients with SSI in the MCA territory who had received IVT between June 2020 and 2022 were included. END was defined as an increase in the total National Institutes of Health Stroke Scale (NIHSS) score by ≥2 or in the motor NIHSS score by ≥1 within the first 72 h of admission. Patients with proximal (pSSI) and distal SSI (dSSI) were analyzed to determine SSI type-specific predictors for END. We evaluated 174 patients with SSI in the MCA territory who underwent IVT. Multivariable logistic regression analysis showed that pSSI (odds ratio [OR] = 0.242; 95% confidence interval [CI], 0.104-0.564; p = .001), lower high-density lipoprotein cholesterol (HDL-C) (OR = 0.150; 95% CI, 0.033-0.682; p = .014), higher blood glucose (OR = 0.858; 95% CI, 0.752-0.979; p = .023), and higher red blood cells count (OR = 1.966; 95% CI, 1.154-3.349; p = .013) were risk factors for END. In patients with pSSI, HDL-C and blood glucose were associated with END. No variable related to END was found in the dSSI group. The proportion of END in patients with SSI in the MCA territory after IVT was not low; therefore, pSSI, HDL-C, blood glucose, and red blood cells should be monitored closely. The frequency and predictors of SSI in the MCA territory differed between pSSI and dSSI.


Morphology and dimensions of the thoracic cord by computer-assisted metrizamide myelography.
Computed tomographic (CT) measurements of the thoracic spine and its contents were obtained in 33 patients undergoing metrizamide myelography for various spinal disorders. Twenty-eight of these patients had symptoms referable to the cervical or lumbar region and form the basis of this study. Five patients had symptoms referable to the thoracic spine. Sagittal and coronal CT measurements of the thoracic cord and subarachnoid space were obtained in all cases. In addition, macroscopic measurements of the thoracic cord were obtained from 10 autopsies for correlation with the CT findings. The technical aspects of the measurements are discussed; the normal morphology of the thoracic cord and thecal sac is presented; and the metrizamide CT pattern associated with pathologic lesions involving the thoracic cord is analyzed.


Combination therapy for myelomatosis.
Twenty-eight patients with multiple myeloma have been treated with a quadruple chemotherapeutic regimen consisting of 1, 3 bis (2-chloroethyl)-1-nitrosourea (BCNU), cyclophosphamide, melphalan, and prednisolone. Nineteen new patients and nine who had escaped from previous single-agent therapy were included in the study. The results to date, on eight criteria of response, seem to be superior to those obtained from previous chemotherapeutic regimens. The study has been in progress for 18 months and only three patients have died. Only one who had not received previous therapy died, and she had complicating hyperparathyroidism, which almost certainly contributed to her death.


State-of-the-art anterior cruciate ligament tears: A primer for primary care physicians.
The purpose of this article is to provide primary care physicians and other members of the medical community with an updated, general review on the subject of anterior cruciate ligament (ACL) tears. We aim to enhance awareness of these injuries and to prepare those practicing in the primary care setting to address these injuries. Because ACL injuries are quite common, it is very likely that a primary care physician will encounter these injuries and need to address them acutely. The current literature is replete with new concepts and controversies regarding ACL injuries, and this article provides a concise review for our target audience in regard to the care of a patient with an ACL injury. This article is composed of an overview with current epidemiologic data, basic anatomy and physiology, clinical presentation, physical examination findings, imaging modalities, and treatment options. After reading this short article, a medical care provider should understand ACL injuries and their appropriate management.


The outcome of a temporomandibular joint compression test for the diagnosis of arthralgia is confounded by concurrent myalgia.
Pain in the orofacial region may originate from different structures, and one challenge for the clinician is to determine the primary origin of pain reported by the patient. In clinical practice, it is important to discriminate between a temporomandibular joint (TMJ) pain disorder and jaw muscle pain; therefore, tests that are proposed for such purposes warrant evaluation. The aim of the present study was to evaluate the outcome of a TMJ compression test in relation to a Diagnostic Criteria for Temporomandibular Disorders (DC/TMD) arthralgia diagnosis. A study population (n = 300), randomly selected from the adult population in Västerbotten, Sweden, was examined according to the DC/TMD criteria and with a TMJ compression test. This test is comprised of forceful unilateral biting for 20 s on a wooden spatula in the first molar region. Familiar pain on the contralateral side to the clenching side was considered a positive test outcome. Positive contralateral outcome of the TMJ compression test was associated with an arthralgia diagnosis (B = 1.737; OR 5.7, 95% CI 3.3-9.9). This association was confounded by concurrent myalgia (B = 1.737 → B = 0.996, 42.7%). In a general population, a negative TMJ compression test was strongly associated with the absence of a contralateral TMJ arthralgia diagnosis according to DC/TMD. The association between a positive TMJ compression test and a DC/TMD arthralgia diagnosis was confounded by the presence of myalgia. Concurrent myalgia renders the usefulness of the TMJ compression test for predicting an arthralgia diagnosis questionable.


An inhibitory alternative splice isoform of Toll-like receptor 3 is induced by type I interferons in human astrocyte cell lines.
Toll-like receptor 3 (TLR3) recognizes viral double-stranded RNA. It stimulates pro-inflammatory cytokine and interferon production. Here we reported the expression of a novel isoform of TLR3 in human astrocyte cell lines whose message is generated by alternative splicing. The isoform represents the N-terminus of the protein. It lacks many of the leucine-rich repeat domains, the transmembrane domain, and the intracellular Toll/interferon-1 receptor domain of TLR3. Type I interferons (interferon-α and interferon-β) induced the expression of this isoform. Exogenous overexpression of this isoform inhibited interferon regulatory factor 3, signal transducers and activators of transcription 1, and Inhibitor of kappa Bα signaling following stimulation. This isoform of TLR3 also inhibited the production of chemokine interferon-γ-inducible protein 10. Our study clearly demonstrated that the expression of this isoform of TLR3 was a negative regulator of signaling pathways and that it was inducible by type I interferons. We also found that this isoform could modulate inflammation in the brain.


Consensus statement of the Society of Critical Care Medicine's Ethics Committee regarding futile and other possibly inadvisable treatments.
Society must always face the reality of limited medical resources and must find mechanisms for distributing these resources fairly and efficiently. One recent approach for distributing limited medical resources has been the development of policies that limit the availability of futile treatments. The objectives of this consensus statement are as follows: a) to define futility and thereby enable a clear discussion of the issues; and b) to identify principles and procedures for resolving cases in which life-sustaining treatment may be futile or inadvisable. A literature review, synthesis, and committee discussion. Treatments should be defined as futile only when they will not accomplish their intended goal. Treatments that are extremely unlikely to be beneficial, are extremely costly, or are of uncertain benefit may be considered inappropriate and hence inadvisable, but should not be labeled futile. Futile treatments constitute a small fraction of medical care. Thus, employing the concept of futile care in decision-making will not primarily contribute to a reduction in resource use. Nonetheless, communities have a legitimate interest in allocating medical resources by limiting inadvisable treatments. Communities should seek to do so using a rationale that is explicit, equitable, and democratic; that does not disadvantage the disabled, poor, or uninsured; and that recognizes the diversity of individual values and goals. Policies to limit inadvisable treatment should have the following characteristics: a) be disclosed in the public record; b) reflect moral values acceptable to the community; c) not be based exclusively on prognostic scoring systems; d) articulate appellate mechanisms; and e) be recognized by the courts. Healthcare organizations that control payment have a profound influence on treatment decisions and should formally address criteria for determining when treatments are inadvisable and should share accountability for those decisions.


Migraine therapeutics in adolescents: a systematic analysis and historic perspectives of triptan trials in adolescents.
OBJECTIVES To conduct a systematic review and analysis of trial data submitted to the US Food and Drug Administration (FDA) to identify possible causes for the failure of pediatric trials of triptans for treatment of migraines. DATA SOURCE The FDA website for drug information and published literature. STUDY SELECTION All pediatric efficacy and pharmacokinetics trial data of drugs used for abortive treatment of migraine submitted to the FDA from January 1, 1999, through December 31, 2011. MAIN OUTCOME MEASURES Patient demographic baseline characteristics, inclusion and exclusion criteria, trial designs, efficacy end points, and pharmacokinetic profiles were analyzed and compared across drug products. RESULTS We analyzed data for sumatriptan succinate nasal spray and zolmitriptan, eletriptan hydrobromide, almotriptan malate, and rizatriptan benzoate tablets. Seven efficacy trials had a randomized, double-blinded, placebo-controlled, parallel-group trial design. In 4 trials, patients were required to have a history of migraine attacks lasting at least 4 hours. High response rates for placebo were observed in all trials, with pain relief at 2 hours ranging from 53% to 57.5%. Nonrandomization of patients with an early placebo response design was used in the rizatriptan trial in 2011. Compared with the rizatriptan trial conducted in 1999, the 2011 rizatriptan trial reduced the placebo response rate by 6% for headache freedom at the 2-hour posttreatment end point owing to study design. The pharmacokinetic profiles between adolescents and adults were statistically similar. CONCLUSIONS High placebo response rates are consistent across all trials and may represent the principal challenge in pediatric trials of drugs for abortive treatment of migraine. Enrichment with selection of subjects with long-lasting migraine attacks is not sufficient to overcome high placebo response rates. Another enrichment strategy, the nonrandomization of patients with an early placebo response, successfully reduces the high placebo response rate for rizatriptan and is a trial design that should be considered for future pediatric trials of abortive migraine therapeutics.


Normalisation with coherent scatter signal: improvements in the calibration procedure of the 57Co-based in vivo XRF bone-Pb measurement.
The feasibility of a normalised calibration variable to account for interpatient variability for in vivo 57Co XRF (X-ray fluorescence) finger bone-lead measurements was assessed. Normalising the lead X-ray intensities to the coherent scatter signal was investigated by experiment and Monte Carlo simulation. The X-ray to coherent ratios for a fixed lead concentration were within 5-10% of the mean, within uncertainty, over a physiologically relevant range of finger bone sizes and overlying tissue thicknesses. This is an acceptable level of variation to introduce, as it is less than the uncertainty of a typical in vivo measurement. Normalisation has several advantages compared with the current method of correcting for interpatient variation, as it eliminates the need for transporting extensive equipment to on-site measurements, reduces the subject dose by a factor of two, and increases the objectivity of the bone-Pb assessment.


Parenting and Digital Media.
Understanding the family dynamic surrounding media use is crucial to our understanding of media effects, policy development, and the targeting of individuals and families for interventions to benefit child health and development. The Families, Parenting, and Media Workgroup reviewed the relevant research from the past few decades. We find that child characteristics, the parent-child relationship, parental mediation practices, and parents' own use of media all can influence children's media use, their attitudes regarding media, and the effects of media on children. However, gaps remain. First, more research is needed on best practices of parental mediation for both traditional and new media. Ideally, this research will involve large-scale, longitudinal studies that manage children from infancy to adulthood. Second, we need to better understand the relationship between parent media use and child media use and specifically how media may interfere with or strengthen parent-child relationships. Finally, longitudinal research on how developmental processes and individual child characteristics influence the intersection between media and family life is needed. The majority of children's media use takes place within a wider family dynamic. An understanding of this dynamic is crucial to understanding child media use as a whole.


The experience of pay for performance in English family practice: a qualitative study.
We conducted an in-depth exploration of family physicians' and nurses' beliefs and concerns about changes to the family health care service as a result of the new pay-for-performance scheme in the United Kingdom (Quality and Outcomes Framework [QOF]). Using a semistructured interview format, we interviewed 21 family doctors and 20 nurses in 22 nationally representative practices across England between February and August 2007. Participants believed the financial incentives had been sufficient to change behavior and to achieve targets. The findings suggest that it is not necessary to align targets to professional priorities and values to obtain behavior change, although doing so enhances enthusiasm and understanding. Participants agreed that the aims of the pay-for-performance scheme had been met in terms of improvements in disease-specific processes of patient care and physician income, as well as improved data capture. It also led to unintended effects, such as the emergence of a dual QOF-patient agenda within consultations, potential deskilling of doctors as a result of the enhanced role for nurses in managing long-term conditions, a decline in personal/relational continuity of care between doctors and patients, resentment by team members not benefiting financially from payments, and concerns about an ongoing culture of performance monitoring in the United Kingdom. The QOF scheme may have achieved its declared objectives of improving disease-specific processes of patient care through the achievement of clinical and organizational targets and increased physician income, but our findings suggest that it has changed the dynamic between doctors and nurses and the nature of the practitioner-patient consultation.


Thrombophilic factors in idiopathic intracranial hypertension: a report of 51 patients and a meta-analysis.
Several studies have suggested that thrombophilic risk factors are more prevalent in individuals with idiopathic intracranial hypertension (IIH), and that a prothrombic state may be involved in the etiopathogenesis of this disease. We examine thrombophilic factors in a group of patients with IIH in relation to obesity. In addition, we reviewed the relevant literature and performed a meta-analysis. Thrombophilia work-up was performed on 51 patients with IIH at least 1 month following their first episode. Samples for the analysis of factor V Leiden (FVL), prothrombin gene variant (PGV) G20210A and methylenetetrahydrofolate reductase (MTHFR) were available in an additional 30 patients, that is 81 patients in all. Meta-analysis was performed. Of the 51 patients 40 were obese. Increased concentrations of fibrinogen, D-Dimer, factor VIII, factor IX and factor XI were found in 15, 7, 7, 6 and 2 patients, respectively, all obese. The circulating anticoagulant, measured by dilute Russell's viper venom time (dRVVT assay), found mainly in obese. All 51 patients were negative for the anticardiolipin antibody (IgG immunoglobulin G) and IgG anti-beta2 glycoprotein I. In the meta-analysis antiphospholipid antibodies were significantly associated with IIH [odds ratio (OR) of 4.25 (1.68-12.60)], similar to the association with high factor VIII [OR = 16.17 (2.87-91.01)], higher plasminogen activator inhibitor-1 (PAI-1) levels [OR = 6.91 (2.28-20.91)], and high lipoprotein (a) [LP(a)] [OR = 3.54 (1.54-8.70)]. Obesity often observed in IIH patients is frequently linked with thrombophilic factors. Thus, we believe that dysmetabolism could be the thrombophilic target for treatment in patients with IIH.


Threshold and spectral sensitivity of vision in medaka Oryzias latipes determined by a novel template wave matching method.
We propose a new analytical method for determining the response threshold in electroretinogram (ERG) in which the wave shows a biphasic slow dc-potential shift. This method uses the recorded wave to the highest intensity stimuli in each wavelength tested as a template wave f(t), and it was compared with other recorded waves obtained under lower intensities g(t). Our test recordings in medaka Oryzias latipes were analogous between the template and the compared waveforms, although there were differences in amplitude and time lag (τ, peak time difference) which occurred as a result of the difference in stimulus intensity. Cross-correlation analysis was applied. Based on the obtained cross-correlation function Cfg(τ) in each comparison, τ was determined as the time lag at which the cross-correlation coefficient Rfg(τ) showed the maximum value. Determined thresholds that were based on both the experimenter's visual inspection and this new method agreed well when the adoption condition was set to satisfy R(τ) ≥ 0.7 and τ ≤ 150 ms in scotopic or τ ≤ 120 ms in photopic conditions. We concluded that this "template wave matching method" is a quick and reliable objective assessment that can be used to determine the threshold. This study analyzed ERG recordings in response to 6 kinds of wavelength light stimuli (380 nm to 620 nm) at different photon flux densities. We report the threshold levels and relative spectral sensitivities in scotopic and photopic vision of medaka.


A fish cytokine related to human IL-3, IL-5, and GM-CSF, induces development of eosinophil/basophil/mast-cell type (EBM) granulocytes.
Interleukin-3 (IL-3), IL-5, and granulocyte-macrophage colony-stimulating factor (GM-CSF) are related cytokines that signal through receptors possessing the β common (βc) chain. As a family, these cytokines combine rather non-specific hematopoietic growth factor properties with a special importance for eosinophils, basophils, and mast cells. In fish the cytokines of this family are called IL-5fam, and the present study, using carp, constitutes their first functional analysis. Carp il-5fam expression was enhanced by stimulation with phytohemagglutinin and killed bacteria. Reminiscent of mammalian IL-3/IL-5/GM-CSF family members, recombinant carp IL-5fam (rcIL-5fam) induced activation of transcription factor STAT5 and efficiently promoted proliferation and colony-formation of eosinophil/basophil/mast-cell type (EBM) granulocytes. Upon addition of recombinant carp βc the growth effect of rcIL-5fam was reduced, suggesting βc participation in the signaling route. In summary, despite differences in individual cytokines and cell populations, fish and mammalian IL-3/IL-5/GM-CSF family members share growth factor functions for non-neutrophil granulocytes.


Improved solitary pancreas transplant graft survival in the modern immunosuppressive era.
The results of solitary pancreas (SP) transplantation have traditionally lagged behind those of simultaneous pancreas-kidney (SPK) transplantation. This is one of the chief factors that has limited the wide-scale application of SP transplantation in nonuremic type I diabetic patients. The purpose of this study is to report our present experience with SP transplantation and compare it to a prior experience. Twenty-three SP transplants (14 PAK, 4 PTA, and 5 PASPK) performed since January 1997 were compared to 56 SP transplants (53 PAK, 1 PTA, and 2 PASPK) performed before 1994. Between 1993 and 1997, SP transplants were not performed because of high morbidity in the early experience. Early SP transplants were performed using bladder drainage of exocrine secretions, and enteric drainage without a Roux-en-Y was used in the recent series. In the early era, immunosuppressive therapy included cyclosporine (CsA), azathioprine (AZA), corticosteroids, and in half of the patients, ALG or OKT3. Recent SP transplants received tacrolimus (TAC). mycophenolate mofetil (MMF), corticosteroids, and induction with either anti-thymocyte globulin (n = 9), OKT3 (n = 1), daclizumab (n = 5), or basiliximab (n = 8). The 1-year Kaplan-Meier patient survival was 85% in the early era and 100% in the recent group of patients (p = 0.08). In the previous era, four patients suffered significant decrement in renal function, necessitating dialysis or kidney transplantation following pancreas transplantation. All patients transplanted since 1997 maintain near prepancreas transplant levels of renal function (mean pretransplant serum creatinine (Cr) 1.3 +/- 0.3 mg/dl vs, mean current Cr 1.4 +/- 0.4 mg/dl, p = NS]. The 1-year Kaplan-Meier graft survival (insulin independence) of recent SP transplants was 87%, whereas for prior SP transplants it was 19% (p = 0.0001). The rate of acute pancreas rejection was significantly different between the two groups. Of early SP transplants, 76% experienced at least one rejection episode within the first year. In contrast, 35% of recent SP transplants suffered acute rejection during the same time period (p = 0.04). Current experience with SP transplantation demonstrates improved graft survival and reduced rejection rates with the use of newer immunosuppressive agents.


Amplified fluorogenic immunoassay for early diagnosis and monitoring of Alzheimer's disease from tear fluid.
Accurate diagnosis of Alzheimer's disease (AD) in its earliest stage can prevent the disease and delay the symptoms. Therefore, more sensitive, non-invasive, and simple screening tools are required for the early diagnosis and monitoring of AD. Here, we design a self-assembled nanoparticle-mediated amplified fluorogenic immunoassay (SNAFIA) consisting of magnetic and fluorophore-loaded polymeric nanoparticles. Using a discovery cohort of 21 subjects, proteomic analysis identifies adenylyl cyclase-associated protein 1 (CAP1) as a potential tear biomarker. The SNAFIA demonstrates a low detection limit (236 aM), good reliability (R2 = 0.991), and a wide analytical range (0.320-1000 fM) for CAP1 in tear fluid. Crucially, in the verification phase with 39 subjects, SNAFIA discriminates AD patients from healthy controls with 90% sensitivity and 100% specificity in under an hour. Utilizing tear fluid as a liquid biopsy, SNAFIA could potentially aid in long-term care planning, improve clinical trial efficiency, and accelerate therapeutic development for AD.


Inhibins in normal male physiology.
Inhibin is a dimeric glycoprotein that suppresses follicle-stimulating hormone (FSH) secretion from the pituitary. Two bioactive forms of inhibin exist, inhibin A and B. The availability of specific immunoassays for each of the isoforms has enabled the study of the individual inhibins and their physiological roles. In the male, inhibin B is the circulating form in all species studied to date except the sheep. Inhibin B is produced in the testis, principally by the Sertoli cells. There are temporal changes in inhibin expression and secretion with the changing role of the Sertoli cell in immature and adult testes. Variations in inhibin B production between species reflect the different patterns of maturation. In the adult, inhibin B levels are positively correlated with Sertoli cell function, sperm number, and spermatogenic status and are negatively correlated with FSH. It appears that the regulation of inhibin B production is mediated by a complex interaction between FSH, Sertoli cells, Leydig cells, and germ cells. Inhibin may also play a role at an autocrine or paracrine level in modulating the actions of activin.


Dosing study on the effectiveness of salicylate/N-acetylcysteine for prevention of noise-induced hearing loss.
The efficacy of three different doses of sodium salicylate (SAL) in combination with one dose of N-acetylcysteine (NAC) to prevent noise-induced hearing loss was studied in chinchillas. After obtaining baseline-hearing thresholds, the chinchillas were randomly assigned to one of four treatment groups: three sets were injected intraperitoneally with 325 mg/kg NAC combined with 25, 50, or 75 mg/kg SAL, and a separate control group was injected with an equal volume of saline. Animals were injected twice daily for 2 days prior to and 1 hour before the noise exposure (6 hours to a 105-dB Standard Pressure Level octave band noise centered at 4 kHz). Immediate post-noise hearing thresholds were obtained followed by post-noise treatments at 1 hour then twice-daily for 2 days. Hearing tests continued at 1, 2, and 3 weeks post-noise, and immediately after the last hearing test, animals' cochleae were stained for hair cell counts. All the groups showed hearing improvement until week 2. However, at week 3, saline treated animals demonstrated a 17-33 dB SPL permanent threshold shift (PTS) across the test frequencies. Hearing loss was lowest in the 50 SAL/325 NAC mg/kg group (all frequencies, P < 0.001), and although PTS was reduced in the 25 and 75 mg/kg SAL dosage groups compared to the saline group, only the 75 mg/kg SAL group was significantly different at all but 2 kHz frequency. Coupled with the hearing loss, outer hair cell (OHC) loss was maximal in the 4-8 kHz cochlear region of saline treated animals. However, there was a substantial reduction in the mean OHC loss of the NAC plus 50 or 75 mg/kg (but not the 25 mg/kg) SAL groups. These findings suggest that SAL in combination with NAC is effective in reducing noise damage to the cochlea, but SAL has a relatively narrow therapeutic dosing window.


A cross-sectional study to determine the normal corneal epithelial thickness in Indian population using 9-mm wide optical coherence tomography scans.
To study the corneal epithelial thickness with 9-mm scans of optical coherence tomography in normal Indians with appropriate representation of all age groups. This was a cross-sectional observational study. 263 patients were divided into the age groups 5-20 years, 21-35 years, 36-50 years and more than 51 years were recruited for the study. All patients underwent a detailed ophthalmic examination. Patients found to have any ocular surface or intraocular disease condition (except cataract and refractive error), or who had undergone any ophthalmic surgery in the past, or had corneal topography changes suggestive of corneal ectasias (screened in patients with astigmatism more than 3 diopters) or had been continuously using any topical medication in either eye for a period of 3 months or more with the last instillation being within 1 month of inclusion in the study were excluded. All subjects underwent corneal epithelial thickness measurement with anterior segment optical coherence tomography (AS-OCT) on the Avanti OCT (Model RTVueXR1002, Optovue, USA). The corneal epithelial thickness (CET) data from 25 sectors in each eye were analyzed. 263 right and left eyes of 263 patients were analyzed in the study. Mean CETs in the central 2 mm zone were 54.13 ± 4.51 μm and 54.37 ± 3.75 μm for the right and left eyes, respectively. The superior peripheral sectors and inferior paracentral sectors were the thinnest and the thickest sectors, respectively, in both eyes. CET parameters for Indian eyes are comparable to those reported from racially distinct and geographically distant study subjects.


Using the Rey Auditory Verbal Learning Test (RAVLT) to differentiate alzheimer's dementia and behavioural variant fronto-temporal dementia.
In patients with focal lesions, patterns of learning, retrieval, and recognition deficits vary according to site of damage. Because different brain regions are affected by the underlying pathology in Alzheimer's dementia (AD) and behavioral variant fronto-temporal dementia (bvFTD), one might predict that the two disorders would result in different sorts of memory deficits on the Rey Auditory Verbal Learning Test (RAVLT). The aim of this investigation was to find a way to differentiate AD, bvFTD, and normal controls (NC) reliably based on RAVLT scores from retrospective samples of 82 Italian and 43 Australian participants. Results indicated that the groups differed on measures of learning, retroactive interference, delayed recall, and delayed recognition. Although delayed recall distinguished participants in the three groups across both samples, no one set of cut-offs could be obtained with adequate sensitivity and specificity. However, when we created a combined score (the "RAVLT Memory Efficiency Index": {[(delayed recall A/15)/(RAVLT Trials 1-5/75)] + [(delayed recognition hits/15) - (false positive/total number of distractors)]}), we were able to find cut-offs that differentiated the groups with good sensitivity and specificity across variations in RAVLT methodology, participant samples, and languages. This index will increase the usefulness of the RAVLT in differential diagnoses of early dementia.


Risk and Prognostic Factors for Multidrug-Resistant Acinetobacter Baumannii Complex Bacteremia: A Retrospective Study in a Tertiary Hospital of West China.
The increasing prevalence and mortality of multidrug-resistant (MDR) Acinetobacter baumannii complex-associated infections, especially bacteremia, in health care settings poses a great threat to public health. We proceeded to investigate the risk and prognostic factors for MDR A. baumannii complex bacteremia in mainland China. This retrospective study was conducted at West China Hospital from January 2009 to December 2013. Using a computer-assisted microbiology laboratory database, patients with MDR A. baumannii complex bacteremia were included as the case group, while those infected with non-MDR A. baumannii complex were selected as the control group. The clinical data were collected and analyzed. There were 241 non-duplicated A. baumannii complex blood isolates identified in our research, with the overall rate of multidrug resistance reaching 75.52% over the past five years. Using multivariate logistic analysis, being in the intensive care unit (ICU) (adjusted odds ratio [aOR], 5.84; 95% confidence interval [CI], 1.67-20.44), increased Pittsburgh bacteremia score (aOR, 6.55; 95% CI, 1.27-33.70) and use of carbapenem (aOR, 8.90; 95% CI, 1.71-46.30) were independent risk factors for MDR acquisition among patients with A. baumannii complex bacteremia. Older age (aOR, 1.02; 95% CI, 1.00-1.04), being post-transplantation (aOR, 5.21; 95% CI, 1.13-24.04), having a higher Pittsburgh bacteremia score (aOR, 2.19; 95% CI, 1.08-4.47) and having a lower level of albumin (aOR, 0.93; 95% CI, 0.88-0.99) were identified as independent risk factors for 30-day mortality in patients with MDR A. baumannii complex bacteremia. In conclusion, our research revealed the risk factors associated with acquisition of and mortality from MDR A. baumannii complex bacteremia, which may be used to prioritize infection control practices and prognostic evaluations.


Effect of weak static magnetic fields on the development of cultured skeletal muscle cells.
We studied the effect produced on the development and functional activity of skeletal muscle cells from newborn Wistar rats in primary culture by weak static magnetic fields (WSMF; 60-400 µT) with a high capacity of penetrating the biological media. To reduce the impact of external magnetic fields, cells were cultured at 37 °C in a multilayered shielding chamber with the attenuation coefficient equal to 160. WSMF inside the chamber was created by a circular permanent magnet. We found that the application of WSMF with the magnetic field strength only a few times that of the geomagnetic field can accelerate the development of skeletal muscle cells, resulting in the formation of multinuclear hypertrophied myotubes. WSMF was shown to induce 1.5- to 3.5-fold rise in the concentration of intracellular calcium [Ca(2+)]i due to the release of Ca(2+) from the sarcoplasmic reticulum (SR) through ryanodine receptors (RyR), which increases in the maturation of myotubes. We also found that fully differentiated myotubes at late stages of development were less sensitive to WSMF, manifesting a gradual decrease in the frequency of contractions. However, myotubes at the stage when electromechanical coupling was forming dramatically reduced the frequency of contractions during the first minutes of their exposure to WSMF.


Nitrogen in aquatic ecosystems.
Aquatic ecosystems respond variably to nutrient enrichment and altered nutrient ratios, along a continuum from fresh water through estuarine, coastal, and marine systems. Although phosphorus is considered the limiting nutrient for phytoplankton production in freshwater systems, the effects of atmospheric nitrogen and its contribution to acidification of fresh waters can be detrimental. Within the estuarine to coastal continuum, multiple nutrient limitations occur among nitrogen, phosphorus, and silicon along the salinity gradient and by season, but nitrogen is generally considered the primary limiting nutrient for phytoplankton biomass accumulation. There are well-established, but nonlinear, positive relationships among nitrogen and phosphorus flux, phytoplankton primary production, and fisheries yield. There are thresholds, however, where the load of nutrients to estuarine, coastal and marine systems exceeds the capacity for assimilation of nutrient-enhanced production, and water-quality degradation occurs. Impacts can include noxious and toxic algal blooms, increased turbidity with a subsequent loss of submerged aquatic vegetation, oxygen deficiency, disruption of ecosystem functioning, loss of habitat, loss of biodiversity, shifts in food webs, and loss of harvestable fisheries.


Diaphragmatic left ventricular aneurysm. Clinical features, surgical treatment, and long-term follow-up in 22 patients.
Although the formation of a left ventricular aneurysm (LVA) is a common and well-recognized complication of myocardial infarction (MI), diaphragmatic LVA is a rare clinical entity. Of 354 consecutive patients who underwent LVA resection, we describe the clinical features and surgical results of 22 patients (6%) with diaphragmatic LVA. All patients had a history of MI. The principal clinical indication for surgery was heart failure in nine patients, angina pectoris in ten patients, and recurrent ventricular tachycardia unresponsive to medical therapy in three patients. A ventricular septal defect was present in two patients, and moderate to severe mitral regurgitation was present in four patients. Three of the four surgical deaths (operative mortality, 18%) occurred in patients with mitral regurgitation or with ventricular septal defect. Eleven patients are alive at a mean follow-up of 40 months. Six of them are asymptomatic and two have angina at a higher level of physical activity than before surgery. Notable differences exist in the clinical presentation and surgical findings between patients with diaphragmatic and anterior LVA.


Kinin-induced prostaglandin synthesis by renal papillary collecting tubule cells in culture.
Cells having morphological and histochemical properties of collecting tubules were isolated from rabbit renal papillae. Confluent monolayer cultures of these renal papillary collecting tubule (RPCT) cells formed hemicysts and adhered with morphological asymmetry to Millipore filters. Cultures of 1-day-old RPCT cells synthesized cAMP in response to arginine vasopressin (AVP) (half-maximal response to 10(-10) M), oxytocin, and parathyroid hormone (half-maximal responses at 5 X 10(-9) M) but not to adrenergic agents. After 10 days of growth (fourfold increase in cell number) RPCT cells retained the same pattern of histochemical and hormonal responses as 1-day-old cells. Hormones were tested for their influence on the release of immunoreactive prostaglandins (iPG) by RPCT cells; the major product under both basal and stimulated conditions was iPGE2. At very low concentrations (greater than or equal to 10(-10) M), bradykinin, lysyl-bradykinin, and methionyl-lysyl-bradykinin caused four- to sixfold increases in the rate of iPGE2 formation within 3 min; smaller (less than twofold) increases were observed with relatively high concentrations of epinephrine (10(-5) M), norepinephrine (10(-5) M), and angiotensin II (10(-7) M), but only after longer incubations. Significantly, neither AVP (10(-7) M) nor [deamino]AVP (10(-7) M) caused prostaglandin release by RPCT cells. Our results indicate that kinins can act directly on the collecting tubule to elicit PGE2 formation; furthermore, this effect of kinins may be natriuretic, since PGE2 has been shown to inhibit Na+ resorption by the medullary collecting tubule and thick ascending limb.


Denaturation mapping of Saccharomyces cerevisiae.
Optical mapping of DNA provides large-scale genomic information that can be used to assemble contigs from next-generation sequencing, and to detect rearrangements between single cells. A recent optical mapping technique called denaturation mapping has the advantage of using physical principles rather than the action of enzymes to probe genomic structure. Denaturation mapping uses fluorescence microscopy to image the pattern of partial melting along a DNA molecule extended in a channel of cross-section 120 nm at the heart of a nanofluidic device. We used denaturation mapping to locate single DNA molecules on the yeast genome (12.1 Mbp) by comparing images to a computationally predicted map for the entire genome sequence. By locating 84 molecules we assembled an optical map of the yeast genome with > 50% coverage.


A feasibility study of digital single-operator cholangioscopy for diagnostic and therapeutic procedure (with videos).
Recently, the novel SpyGlass DS Direct Visualization system (SPY DS) has become available. This system offers several advantages over the conventional SPYGlass system. This study evaluated the clinical feasibility and efficacy of diagnostic and therapeutic procedures for biliary disorder using SPY DS.In this retrospective study, consecutive patients who had biliary disorder were enrolled between November 2015 and February 2016. All patients could not be diagnosed or treated by standard endoscopic retrograde cholangiopancreatography in our hospital or at another hospital.A total of 28 consecutive patients (21 men and 7 women; median age, 73 years; age range, 55-87 years) were retrospectively enrolled in this study. Among them, diagnostic procedure was performed in 20 patients, and 8 patients underwent therapeutic procedures. The technical success rate for diagnostic procedures was 100% (20/20). Diagnostic accuracy was 100% (19/19). The technical success rate for therapeutic procedures was 88% (7/8). Among these 8 patients, 4 patients with common bile duct stones underwent electrohydraulic lithotripsy. One patient successfully underwent guidewire insertion to remove a migrated plastic stent. The 3 remaining patients underwent SPY DS to insert a guidewire for left bile duct obstruction and for posterior bile duct branch. In the patient who underwent guidewire insertion for left hepatic bile duct obstruction cause by primary sclerosing cholangitis, we could not advance the guidewire into the left hepatic bile duct. No adverse events were seen. Median SPY DS insertion time was 21 min (range, 8-32 min).Single-operator cholangioscopy using SPY DS was feasible and had a marked clinical impact in patients with biliary disease. Additional case reports and prospective studies are needed to examine further applications of this system.


Reflectance spectra analysis for mucous assessment.
This review report represents an overview of research and development on medical hyperspectral imaging technology and its applications. Spectral imaging technology is attracting attention as a new imaging modality for medical applications, especially in disease diagnosis and image-guided surgery. Considering the recent advances in imaging, this technology provides an opportunity for two-dimensional mapping of oxygen saturation (SatO2) of blood with high accuracy, spatial spectral imaging, and its analysis and provides detection and diagnostic information about the tissue physiology and morphology. Multispectral imaging also provides information about tissue oxygenation, perfusion, and potential function during surgery. Analytical algorithm has been examined, and indication of accurate map of relative hemoglobin concentration and SatO2 can be indicated with preferable resolution and frame rate. This technology is expected to provide promising biomedical information in practical use. Several studies suggested that blood flow and SatO2 are associated with gastrointestinal disorders, particularly malignant tumor conditions. The use and analysis of spectroscopic images are expected to potentially play a role in the detection and diagnosis of these diseases.


Endovascular thrombectomy for stroke: current best practice and future goals.
Endovascular thrombectomy for large vessel ischaemic stroke substantially reduces disability, with recent positive randomised trials leading to guideline changes worldwide. This review discusses in detail the evidence provided by recent randomised trials and meta-analyses, the remaining areas of uncertainty and the future directions for research. The data from existing trials have demonstrated the robust benefit of endovascular thrombectomy for internal carotid and proximal middle cerebral artery occlusions. Uncertainty remains for more distal occlusions where the efficacy of alteplase is greater, less tissue is at risk and the safety of endovascular procedures is less established. Basilar artery occlusion was excluded from the trials, but with a dire natural history and proof of principle that rapid reperfusion is effective, it seems reasonable to continue treating these patients pending ongoing trial results. There has been no evidence of heterogeneity in treatment effect in clinically defined subgroups by age, indeed, those aged >80 years have at least as great an overall reduction in disability and reduced mortality. Similarly there was no heterogeneity across the range of baseline stroke severities included in the trials. Evidence that routine use of general anaesthesia reduces the benefit of endovascular thrombectomy is increasing and conscious sedation is generally preferred unless severe agitation or airway compromise is present. The impact of time delays has become clearer with description of onset to imaging and imaging to reperfusion epochs. Delays in the onset to imaging reduce the proportion of patients with salvageable brain tissue. However, in the presence of favourable imaging, rapid treatment appears beneficial regardless of the onset to imaging time elapsed. Imaging to reperfusion delays lead to decay in the clinical benefit achieved, particularly in those with less robust collateral flow. The brain imaging options to assess prognosis have various advantages and disadvantages, but whatever strategy is employed must be fast. Ongoing trials are investigating extended time windows, using advanced brain imaging selection. There is also a need for further technical advances to maximise rates of complete reperfusion in the minimum time.