A comparison between land and sand-based tests for beach volleyball assessment.
Vertical-jumping ability is critical for success in beach volleyball. However, as beach volleyball is a relatively new sport, its testing procedures have largely been adopted from the indoor game and are consequently performed on firm surfaces. The purpose of this paper was to determine whether vertical-jumping ability is specific to the test surface (i.e., wood or sand). Eighteen beach volleyball players performed 4 different vertical jumps on a wood surface or on the sand, followed by the alternate surface, in a random, counterbalanced order. Correlation coefficients were calculated to determine the degree of association between the 4 jumps and between the test results on the 2 surfaces. When compared with the land condition, all jump heights were significantly lower when performed on sand (p<0.05). There was however, a significant correlation between the land and sand results for all jumps (mean r=0.93; p<0.05). While all 4 vertical jump variations were significantly correlated with each other (mean r=0.91; p<0.05), the correlation between static jumps and the spike jump (3-step run up) tended to be lower. It is likely that vertical jump height on sand is lower than on land due to a reduction in the ground reaction force. However, despite this, the strong correlation between land and sand scores suggests that vertical-jumping ability exists as a general quality and is not greatly influenced by test surface in the subjects tested. This suggests that land-based tests can be used to assess sand jumping ability in experienced beach volleyball players.


Method for collecting and immobilizing individual cumulus cells enabling quantitative immunofluorescence analysis of proteins.
Most immunofluorescence methods rely on techniques dealing with a very large number of cells. However, when the number of cells in a sample is low (e.g., when cumulus cells must be analyzed from individual cumulus-oocyte complexes), specific techniques are required to conserve, fix, and analyze cells individually. We established and validated a simple and effective method for collecting and immobilizing low numbers of cumulus cells that enables easy and quick quantitative immunofluorescence analysis of proteins from individual cells. To illustrate this technique, we stained proprotein of a disintegrin and metalloproteinase with thrombospondin-like repeats-1 (proADAMTS-1) and analyzed its levels in individual porcine cumulus cells.


T lymphocytes mediating protection and cellular cytolysis during the course of Mycobacterium tuberculosis infection. Evidence for different kinetics and recognition of a wide spectrum of protein antigens.
Recent evidence suggests the existence of at least two pathways of acquired specific resistance to Mycobacterium tuberculosis infection; the first consisting of cytokine-mediated activation of parasitized host cells by protective T cells, and the second involving the lysis of these cells by cytolytic T cells. Evidence presented in this report shows that both of the above mechanisms are operative in experimentally infected mice, but that they differ markedly in terms of their kinetics of emergence and loss. It was found that protective T cell activity was acquired very early during the course of the infection, and was temporally associated with the onset of bacterial elimination; however, cytolytic activity did not peak until 10 to 20 days later. This report shows further that the target Ag of these effector T cell populations were apparently numerous with no evidence for preferential recognition of a few immunodominant Ag. In view of the preponderance of target proteins in the bacterial filtrate, we present the hypothesis that such proteins secreted or otherwise leaked from the dividing mycobacterium are pinocytosed from the phagosome and used by the infected macrophage as the key protective Ag leading to T cell sensitization. This hypothesis thus explains the preferential requirement for the viable bacterium in the generation of specific resistance, and further explains why protective immunity is generated even while the organism is still multiplying in an apparently unrestrained manner.


The impact of unilateral brain damage on anticipatory grip force scaling when lifting everyday objects.
The scaling of our finger forces according to the properties of manipulated objects is an elementary prerequisite of skilled motor behavior. Lesions of the motor-dominant left brain may impair several aspects of motor planning. For example, limb-apraxia, a tool-use disorder after left brain damage is thought to be caused by deficient recall or integration of tool-use knowledge into an action plan. The aim of the present study was to investigate whether left brain damage affects anticipatory force scaling when lifting everyday objects. We examined 26 stroke patients with unilateral brain damage (16 with left brain damage, ten with right brain damage) and 21 healthy control subjects. Limb apraxia was assessed by testing pantomime of familiar tool-use and imitation of meaningless hand postures. Participants grasped and lifted twelve randomly presented everyday objects. Grip force was measured with help of sensors fixed on thumb, index and middle-finger. The maximum rate of grip force was determined to quantify the precision of anticipation of object properties. Regression analysis yielded clear deficits of anticipation in the group of patients with left brain damage, while the comparison of patient with right brain damage with their respective control group did not reveal comparable deficits. Lesion-analyses indicate that brain structures typically associated with a tool-use network in the left hemisphere play an essential role for anticipatory grip force scaling, especially the left inferior frontal gyrus (IFG) and the premotor cortex (PMC). Furthermore, significant correlations of impaired anticipation with limb apraxia scores suggest shared representations. However, the presence of dissociations, implicates also independent processes. Overall, our findings suggest that the left hemisphere is engaged in anticipatory grip force scaling for lifting everyday objects. The underlying neural substrate is not restricted to a single region or stream; instead it may rely on the intact functioning of a left hemisphere network that may overlap with the left hemisphere dominant tool-use network.


In vivo and In vitro Anti-Inflammatory Activity of Indazole and Its Derivatives.
The inflammatory response is closely intertwined with the process of repair. However in some diseases the inflammatory response may be exaggerated and sustained without apparent benefit and even with severe adverse complications. For decades, we have been primarily relying upon Nonsteroidal (NSAID) and Steroidal Anti-Inflammatory agents for management of various inflammatory conditions. However, adverse effects of these drugs are severe which often leads to patient's non-compliance with inadequate relief. Therefore, there has been a constant pursuit to develop newer anti - inflammatory treatment with fewer side effects. The study was designed to investigate the possible anti- inflammatory activity of indazole, its derivatives and to further investigate the possible cellular mechanisms underlying the anti-inflammatory effect. Carrageenan induced hind paw oedema in rats was employed to study the acute anti-inflammatory activity of indazole and its derivatives. Further, the role of cyclooxygenase - 2, pro-inflammatory cytokines like Tumour Necrosis Factor - α, Interleukin - 1β and free radical scavenging activity (LPO, DPPH and NO) in the action of indazole and its derivatives was investigated using in vitro assays. SPSS version 16.0 software was used for analyse the anti-inflamatory data. The IC50 values of indazole and its derivatives obtained in in vitro experiments were calculated by linear regression analysis. Indazole and its derivatives significantly, dose dependently and time dependently inhibited carrageenan induced hind paw oedema. In addition, the test compounds inhibited cyclooxygenase-2, pro-inflammatory cytokines and free radicals in a concentration dependent manner. The results of the present study revealed the potential anti-inflammatory action of investigated indazoles. The inhibition of cyclooxygenase -2, cytokines and free radicals may contribute to the anti-inflammatory effect of the test compounds.


Multicenter Prospective Phase II Trial of Neoadjuvant Dose-Dense Gemcitabine Plus Cisplatin in Patients With Muscle-Invasive Bladder Cancer.
Purpose Neoadjuvant chemotherapy followed by radical cystectomy (RC) is a standard of care for the management of muscle-invasive bladder cancer (MIBC). Dose-dense cisplatin-based regimens have yielded favorable outcomes compared with standard-dose chemotherapy, yet the optimal neoadjuvant regimen remains undefined. We assessed the efficacy and tolerability of six cycles of neoadjuvant dose-dense gemcitabine and cisplatin (ddGC) in patients with MIBC. Patients and Methods In this prospective, multicenter phase II study, patients received ddGC (gemcitabine 2,500 mg/m2 on day 1 and cisplatin 35 mg/m2 on days 1 and 2) every 2 weeks for 6 cycles followed by RC. The primary end point was pathologic downstaging to non-muscle-invasive disease (< pT2N0). Patients who did not undergo RC were deemed nonresponders. Pretreatment tumors underwent next-generation sequencing to identify predictors of chemosensitivity. Results Forty-nine patients were enrolled from three institutions. The primary end point was met, with 57% of 46 evaluable patients downstaged to < pT2N0. Pathologic response correlated with improved recurrence-free survival and overall survival. Nineteen patients (39%) required toxicity-related dose modifications. Sixty-seven percent of patients completed all six planned cycles. No patient failed to undergo RC as a result of chemotherapy-associated toxicities. The most frequent treatment-related toxicity was anemia (12%; grade 3). The presence of a presumed deleterious DNA damage response (DDR) gene alteration was associated with chemosensitivity (positive predictive value for < pT2N0 [89%]). No patient with a deleterious DDR gene alteration has experienced recurrence at a median follow-up of 2 years. Conclusion Six cycles of ddGC is an active, well-tolerated neoadjuvant regimen for the treatment of patients with MIBC. The presence of a putative deleterious DDR gene alteration in pretreatment tumor tissue strongly predicted for chemosensitivity, durable response, and superior long-term survival.


Induction of surfactant protein (SP-A) biosynthesis and SP-A mRNA in activated type II cells during acute silicosis in rats.
The synthesis of the major surfactant protein, SP-A, was studied in activated alveolar type II cells isolated from the lungs of rats exposed to silica by intratracheal instillation. Exposure of rats to silica resulted in large increases in the levels of disaturated phosphatidylcholine and SP-A in the extracellular and intracellular surfactant compartments. Isolated type II cells were used to determine if the observed increases in SP-A were associated with increased SP-A synthesis. Type II cells were isolated by a combination of elastase digestion, centrifugal elutriation, and differential adherence on IgG-coated petri dishes. Type II cells from silica-treated lungs were separated into two populations, designated type IIA and type IIB. The type IIB, or activated population, consisted of type II cells that were larger than normal type II cells and, in addition, contained larger and more numerous lamellar bodies than normal type II cells. Type IIB cells contained 4.3-fold higher levels of SP-A compared to normal type II cells. SP-A synthesis was measured by incubating freshly isolated cells with [35S]Translabel (70% [35S]methionine, 15% [35S]cysteine) for up to 4 h in methionine-free medium, followed by immunoprecipitation of newly synthesized protein. The rate of SP-A synthesis was increased approximately 6.7-fold in the activated type II cells. Analysis of the newly synthesized protein by one-dimensional SDS-PAGE indicated three intracellular forms of SP-A with molecular weights of approximately 26,000, 30,000, and 34,000. In type II cells from control rats, the 34-kD protein accounted for approximately 93% of the newly synthesized SP-A after 4 h of incubation; only a small amount of radioactivity was associated with the lower molecular weight species. The increased biosynthesis of SP-A in the activated type II cells was associated with a 7.3-fold increase in the level of SP-A mRNA. These results indicate that the content and synthesis of SP-A are both highly elevated in activated type II cells and that these increases may be due to increased levels of SP-A mRNA.


Platelet phospholipase C activity in salt-dependent hypertension.
In spontaneously hypertensive rats (SHR), enhanced responsiveness of phospholipase C has been reported in various cells and tissues. In SHR and in some patients with essential hypertension particularly, the increased phospholipase C responsiveness of platelets has been described as involved in the hyperreactivity to thrombin. To determine the relation between such an enzymic abnormality and hypertension, the platelet phospholipase C activity was investigated in various models of experimental hypertension (i.e., in the Dahl salt-resistant and salt-sensitive strains inbred by John Rapp at Toledo, Ohio, SR/Jr and SS/Jr, respectively) fed either on a low or a high NaCl-containing diet, and in deoxycorticosterone acetate (DOCA)-salt hypertensive rats. In phosphorus-32-prelabeled platelets, phospholipase C was determined by measurement of the thrombin-induced [32P]phosphatidic acid formation; the labeling of the P47 protein with 32P was also measured. In parallel experiments, the platelet reactivity was assessed by measurement of the thrombin-induced serotonin release. Under thrombin (0.05-0.5 units/ml) stimulation, phospholipase C activity, [32P]P47 labeling, and serotonin release were significantly increased in SS/Jr rats fed a high NaCl diet compared with SS/Jr rats fed a low NaCl diet. NaCl-rich diet did not modify phospholipase C in SR/Jr rats. Platelet reactivity and phospholipase C responsiveness were also normal in DOCA-salt hypertensive rats compared with controls.(ABSTRACT TRUNCATED AT 250 WORDS)


Functional Performance and Balance in the Oldest-Old.
The group of individuals 85 years and over (termed oldest-old) is the fastest-growing population in the Western world. Although daily functional abilities and balance capabilities are known to decrease as an individual grows older, little is known about the balance and functional characteristics of the oldest-old population. The aims of this study were to characterize balance control, functional abilities, and balance self-efficacy in the oldest-old, to test the correlations between these constructs, and to explore differences between fallers and nonfallers in this age group. Forty-five individuals living in an assisted living facility who ambulated independently participated in the study. The mean age was 90.3 (3.7) years. Function was tested using the Late-Life Function and Disability Instrument (LLFDI). Balance was tested with the mini-Balance Evaluation System Test (mini-BESTest) and the Timed Up and Go (TUG) test. Balance self-efficacy was tested with the Activities-Specific Balance Confidence (ABC) scale. The mean total function LLFDI score was 63.2 (11.4). The mean mini-BESTest score was 69.8% (18.6%) and the mean TUG time was 12.6 (6.9) seconds. The mean ABC score was 80.2% (14.2%). Good correlation (r > 0.7) was observed between the ABC and the function component of the LLFDI, as well as with the lower extremity domains. Correlations between the mini-BESTest scores and the LLFDI were fair to moderate (r's range: 0.38-0.62). Age and ABC scores were significant independent explanators of LLFDI score (P = .0141 and P = .0009, respectively). Fallers and nonfallers differed significantly across all outcome measures scores, except for TUG and for the "Reactive Postural Control" and "Sensory Orientation" domains of the mini-BESTest. The results of this study provide normative data regarding the balance and functional abilities of the oldest-old, and indicate a strong association between self-efficacy and function. These results emphasize the importance of incorporating strategies that maintain and improve balance self-efficacy in interventions aimed at enhancing the functional level of this cohort.


High-throughput synthesis and electrochemical screening of a library of modified electrodes for NADH oxidation.
We report the combinatorial preparation and high-throughput screening of a library of modified electrodes designed to catalyze the oxidation of NADH. Sixty glassy carbon electrodes were covalently modified with ruthenium(II) or zinc(II) complexes bearing the redox active 1,10-phenanthroline-5,6-dione (phendione) ligand by electrochemical functionalization using one of four different linkers, followed by attachment of one of five different phendione metal complexes using combinatorial solid-phase synthesis methodology. This gave a library with three replicates of each of 20 different electrode modifications. This library was electrochemically screened in high-throughput (HTP) mode using cyclic voltammetry. The members of the library were evaluated with regard to the surface coverage, midpeak potential, and voltammetric peak separation for the phendione ligand, and their catalytic activity toward NADH oxidation. The surface coverage was found to depend on the length and flexibility of the linker and the geometry of the metal complex. The choices of linker and metal complex were also found to have significant impact on the kinetics of the reaction between the 1,10-phenanthroline-5,6-dione ligand and NADH. The rate constants for the reaction were obtained by analyzing the catalytic currents as a function of NADH concentration and scan rate, and the influence of the surface molecular architecture on the kinetics was evaluated.


Ruxolitinib for Glucocorticoid-Refractory Chronic Graft-versus-Host Disease.
Chronic graft-versus-host disease (GVHD), a major complication of allogeneic stem-cell transplantation, becomes glucocorticoid-refractory or glucocorticoid-dependent in approximately 50% of patients. Robust data from phase 3 randomized studies evaluating second-line therapy for chronic GVHD are lacking. In retrospective surveys, ruxolitinib, a Janus kinase (JAK1-JAK2) inhibitor, showed potential efficacy in patients with glucocorticoid-refractory or -dependent chronic GVHD. This phase 3 open-label, randomized trial evaluated the efficacy and safety of ruxolitinib at a dose of 10 mg twice daily, as compared with the investigator's choice of therapy from a list of 10 commonly used options considered best available care (control), in patients 12 years of age or older with moderate or severe glucocorticoid-refractory or -dependent chronic GVHD. The primary end point was overall response (complete or partial response) at week 24; key secondary end points were failure-free survival and improved score on the modified Lee Symptom Scale at week 24. A total of 329 patients underwent randomization; 165 patients were assigned to receive ruxolitinib and 164 patients to receive control therapy. Overall response at week 24 was greater in the ruxolitinib group than in the control group (49.7% vs. 25.6%; odds ratio, 2.99; P<0.001). Ruxolitinib led to longer median failure-free survival than control (>18.6 months vs. 5.7 months; hazard ratio, 0.37; P<0.001) and higher symptom response (24.2% vs. 11.0%; odds ratio, 2.62; P = 0.001). The most common (occurring in ≥10% patients) adverse events of grade 3 or higher up to week 24 were thrombocytopenia (15.2% in the ruxolitinib group and 10.1% in the control group) and anemia (12.7% and 7.6%, respectively). The incidence of cytomegalovirus infections and reactivations was similar in the two groups. Among patients with glucocorticoid-refractory or -dependent chronic GVHD, ruxolitinib led to significantly greater overall response, failure-free survival, and symptom response. The incidence of thrombocytopenia and anemia was greater with ruxolitinib. (Funded by Novartis and Incyte; REACH3 ClinicalTrials.gov number, NCT03112603.).


Epidural meningioma of the sacral canal. Case report.
Spinal meningiomas are reported infrequently as pure epidural tumors, and they are rarely located at the caudal end of the spine. The unique combination of a wholly epidural tumor confined entirely to the sacral canal has not been previously described. The authors describe the case of a 29-year-old man who presented with coccygeal and left-sided S2-4 dermatomal pain. Examination confirmed sensory loss in the same distribution. A magnetic resonance image revealed an enhancing mass lesion in the sacral canal scalloping the bone at S-2 and S-3. An apparent complete resection was performed. Intraoperatively the authors observed an entirely epidural tumor with a small dural attachment at the most caudal end of the thecal sac. Histological examination confirmed that the tumor was an atypical meningioma. A local recurrence developed within 1 year of surgery, and the patient underwent a hemisacrectomy for tumor removal. An additional recurrence in the lumbosacral spine and multiple pulmonary metastases developed thereafter. In addition to the unique nature of this case, the authors also observed a tumor behaving in a far more aggressive fashion than its histological findings would suggest. This adds to the differential diagnosis of tumors occurring in the sacral canal.


Typical and atypical neuroleptics.
Neuroleptics having dopamine receptor-blocking properties are frequently responsible for the development of movement disorders. This has been known for many years as these adverse events were identified soon after the introduction of these drugs for the treatment of psychiatric disorders. Parkinsonism, acute dystonic reactions, akathisia, and tardive dyskinesias are the different clinical presentations of these disorders. Tardive dyskinesia is the most problematic among them as it may persist even after discontinuation of the offending drug, and become an irreversible phenomenon. The term "tardive dyskinesia" encompasses a variety of clinical phenomena including stereotypic behaviors, dystonia, myoclonus, and tics. Stereotypies and orobuccolingual dyskinesias are the most frequently observed tardive disorders, particularly in the elderly population exposed to neuroleptics, while dystonic phenomena are more prevalent in younger individuals. The development of these disorders is dependent on the potency of the drug, duration of exposure, and a number of predisposing factors, including age, gender, and presence of organic brain disease. The pathophysiology is rather complex and involves changes in the dopamine synapse both at the pre- and postsynaptic level, as well as plastic changes involving transcription factors and activation of different molecular cascades downstream of the dopamine receptor. The introduction of more novel pharmacological agents, like the so-called atypical neuroleptics, has significantly reduced the incidence of these disorders; however, the prescribing physician has to be aware that a lower risk is not synonymous with absence of risk.


Mixing the spacers in azacryptands: effects on halide recognition.
In this work, we report on two new asymmetric dicopper cryptates, characterized by alternate furanyl and p-xylyl spacers. The results of the potentiometric, UV-vis and X-ray diffraction studies are discussed. In particular, for one of the cages in the octaprotonated form, the crystal structure of the complex with nitrate is described. From the point of view of the anion binding in water, the new dicopper cryptates display stronger similarities to each other than to the symmetric analogues (i.e. p-xylyl and furan cryptates). The substitution of even only one spacer modifies the distance between the metal ions. This prevents the development of the CT band, typically accompanying the binding of halides by the furan cryptate, and favors the formation of complexes of different stoichiometry with the linear azide anion, not observed for the symmetric cryptates. The obtained results may be very helpful in the design of new molecular receptors based on dimetallic cryptates, in particular for the tuning of the sensitivity towards specific anionic substrates.


Fenugreek extract as an inducer of cellular death via autophagy in human T lymphoma Jurkat cells.
Drugs used both in classical chemotherapy and the more recent targeted therapy do not have cancer cell specificity and, hence, cause severe systemic side effects. Tumors also develop resistance to such drugs due to heterogeneity of cell types and clonal selection. Several traditional dietary ingredients from plants, on the other hand, have been shown to act on multiple targets/pathways, and may overcome drug resistance. The dietary agents are safe and readily available. However, application of plant components for cancer treatment/prevention requires better understanding of anticancer functions and elucidation of their mechanisms of action. The current study focuses on the anticancer properties of fenugreek, a herb with proven anti-diabetic, antitumor and immune-stimulating functions. Jurkat cells were incubated with 30 to 1500 μg/mL concentrations of 50% ethanolic extract of dry fenugreek seeds and were followed for changes in viability (trypan blue assay), morphology (microscopic examination) and autophagic marker LC3 transcript level (RT-PCR). Incubation of Jurkat cells with fenugreek extract at concentrations ranging from 30 to 1500 μg/mL for up to 3 days resulted in cell death in a dose- and time-dependent manner. Jurkat cell death was preceded by the appearance of multiple large vacuoles, which coincided with transcriptional up-regulation of LC3. GC-MS analysis of fenugreek extract indicated the presence of several compounds with anticancer properties, including gingerol (4.82%), cedrene (2.91%), zingerone (16.5%), vanillin (1.52%) and eugenol (1.25%). Distinct morphological changes involving appearance of large vacuoles, membrane disintegration and increased expression of LC3 transcripts indicated that fenugreek extract induced autophagy and autophagy-associated death of Jurkat cells. In addition to the already known apoptotic activation, induction of autophagy may be an additional mechanism underlying the anticancer properties of fenugreek. This is the first report showing fenugreek as an inducer of autophagy in human cells and further work is needed to define the various intermediates of the autophagic pathway.


NMR spectroscopic and bioinformatic analyses of the LTBP1 C-terminus reveal a highly dynamic domain organisation.
Proteins from the LTBP/fibrillin family perform key structural and functional roles in connective tissues. LTBP1 forms the large latent complex with TGFβ and its propeptide LAP, and sequesters the latent growth factor to the extracellular matrix. Bioinformatics studies suggest the main structural features of the LTBP1 C-terminus are conserved through evolution. NMR studies were carried out on three overlapping C-terminal fragments of LTBP1, comprising four domains with characterised homologues, cbEGF14, TB3, EGF3 and cbEGF15, and three regions with no homology to known structures. The NMR data reveal that the four domains adopt canonical folds, but largely lack the interdomain interactions observed with homologous fibrillin domains; the exception is the EGF3-cbEGF15 domain pair which has a well-defined interdomain interface. (15)N relaxation studies further demonstrate that the three interdomain regions act as flexible linkers, allowing a wide range of motion between the well-structured domains. This work is consistent with the LTBP1 C-terminus adopting a flexible "knotted rope" structure, which may facilitate cell matrix interactions, and the accessibility to proteases or other factors that could contribute to TGFβ activation.


Rapid changes of body weight after a headstand: a metrological analysis.
Despite recent rules from amateur wrestling sport-governing bodies intended to discourage extreme weight loss measures, wrestling culture still includes varied methods to make weight, including holding a headstand position immediately before stepping on the scale. The procedure, according to the notion, will reduce reported mass anywhere between 250 and 500 g (weight between 2.45 and 4.89 N). The aim of this study was to compare any possible differences between the headstand procedure (HS) and a normal (CON) weight measure, using a metrological approach defined by the European Association of National Metrology Institutes. Seventeen adult men were weighed on a force plate before and after doing a headstand or standing normally for 30s. The order of treatment application was assigned randomly. Post-test weight was significantly larger than pre-test (mean ± s.d.) (640.7 ± 62.8 N and 640.3 ± 62.7 N, respectively, p < 0.0001) under both treatments. No treatment vs. time of test interaction was found. No significant difference was found between CON and HS weight (640.6 ± 62.8 N and 640.9 ± 62.9 N, respectively, p=0.3815). The metrological tests suggest that the statistical differences found are related to the force plate measuring errors in every pre-established time interval. The 45 g (0.44 N) difference found between pretest and post-test lies within the uncertainty range identified for the equipment (± 110 g or 1.08 N). In conclusion, a 30-second headstand has no significant effect on registered body weight. The small variations obtained were due to equipment-associated measuring errors. This experiment offers systematic empirical evidence to aid in the elimination of this unjustified practice among the wrestling community.


External auditory canal cholesteatoma and keratosis obturans: the role of imaging in preventing facial nerve injury.
We conducted a retrospective study to compare the clinical characteristics of external auditory canal cholesteatoma (EACC) with those of a similar entity, keratosis obturans (KO). We also sought to identify those aspects of each disease that may lead to complications. We identified 6 patients in each group. Imaging studies were reviewed for evidence of bony erosion and the proximity of disease to vital structures. All 6 patients in the EACC group had their diagnosis confirmed by computed tomography (CT), which demonstrated widening of the bony external auditory canal; 4 of these patients had critical erosion of bone adjacent to the facial nerve. Of the 6 patients with KO, only 2 had undergone CT, and neither exhibited any significant bony erosion or expansion; 1 of them developed osteomyelitis of the temporal bone and adjacent temporomandibular joint. Another patient manifested KO as part of a dermatophytid reaction. The essential component of treatment in all cases of EACC was microscopic debridement of the ear canal. We conclude that EACC may produce significant erosion of bone with exposure of vital structures, including the facial nerve. Because of the clinical similarity of EACC to KO, misdiagnosis is possible. Temporal bone imaging should be obtained prior to attempts at debridement of suspected EACC. Increased awareness of these uncommon conditions is warranted to prompt appropriate investigation and prevent iatrogenic complications such as facial nerve injury.


From technical measures to moral obligations: The management and fate of fragmented human remains following disasters. The case of a plane crash in France in 2015.
This article studies the management of human remains (handling, trajectory, fate, status) and the compromises made by the experts involved in the context of an air disaster that took place in France in 2015. Advances in identification techniques are shown to have had concrete effects on applied practice. On the one hand, the presence of human remains enables: victims can be identified and their deaths formally registered, following which the body can be returned to surviving relatives for a proper funeral. On the other, it obliges: human elements or debris, however small, require experts to decide on their status and legitimate destiny. The tradeoffs between technical, economic, legal, moral, and cultural considerations are forging a new way of working with human remains. A trend can be observed whereby principles that previously applied only to the corpse are being extended to human remains that would have otherwise been excluded.


The presence in normal plasma, serum and platelets of factors that stimulate the production of prostacyclin (PGI2) by cultured endothelial cells.
1. The effect of plasma and serum from normal subjects on the production of prostacyclin by cultured porcine endothelial cells was investigated. 2. Both plasma and serum from all subjects studied significantly stimulated the production of prostacyclin by cultured endothelial cells, measured by the radioimmunoassay of its stable metabolite 6-oxoprostaglandin F1 alpha. 3. Serum caused a consistently greater stimulation than plasma from the same individual. The stimulation was dose-dependent and inhibited by indomethacin. Heparin added to serum also inhibited this response. 4. Extracts from isolated washed platelets were tested for their ability to increase prostacyclin production. Extracts from platelets which had been induced to aggregate and release their granule contents in response to thrombin, caused stimulation. 5. These results indicated the invariable presence in plasma and serum of factors that stimulate the production of prostacyclin by endothelial cells in vitro. At least one of these factors is derived from platelets. These factors may be involved in the regulation of prostacyclin production by the vascular endothelium under normal conditions and in disease states.


Quantitative thermal microscopy using thermoelectric probe in passive mode.
A scanning thermal microscope working in passive mode using a micronic thermocouple probe is presented as a quantitative technique. We show that actual surface temperature distributions of microsystems are measurable under conditions for which most of usual techniques cannot operate. The quantitative aspect relies on the necessity of an appropriate calibration procedure which takes into account of the probe-to-sample thermal interaction prior to any measurement. Besides this consideration that should be treated for any thermal contact probing system, the main advantages of our thermal microscope deal with the temperature available range, the insensitivity to the surface optical parameters, the possibility to image DC, and AC temperature components up to 1 kHz typically and a resolution limit related to near-field behavior.


[Chronic peripheral arterial disease induced by cocaine].
Cocaine induced acute peripheral thrombosis, though a rare complication, has been described in the literature. Although there are reports describing the chronic effects of cocaine on the peripheral arterial system, there are no published cases of this complication when other risk factors are lacking. We report on a 22 year old female patient, with intranasal consumption of 3 grams of cocaine per week for a year, who consulted for intermittent claudication at 200 meters, associated to left lower limb pain and paresthesiae for the last two months. Arterial Doppler ultrasonography showed a stenosis greater than 70% in the superficial left femoral artery. Other probable etiologies were excluded. Treatment was initiated with acetylsalicylic acid, cilostazol and graded physical exercise, associated to support therapy in order to maintain cocaine consumption avoidance, with good response. This case emphasizes the relevance of patients information, as most people ignore the cardiovascular complication of this addiction. It is also essential to inquire about cocaine consumption in young patients with peripheral arteriopathy and no apparent risk factors.


Characterization of a novel snake venom component: Kazal-type inhibitor-like protein from the arboreal pitviper Bothriechis schlegelii.
Snake venoms are composed mainly of a mixture of proteins and peptides. Notably, all snake venom toxins have been assigned to a small number of protein families. Proteomic studies on snake venoms have recently identified the presence of Kazal-type inhibitor-like proteins in the neotropical arboreal snakes Bothriechis schlegelii and Bothriechis supraciliaris. In the present study, a Kazal-type component from B. schlegelii, named Kazal-type inhibitor-like protein (KTIL), has been completely sequenced and characterized for the first time. This protein, which contains 54 amino acid residues, shows sequence similarity to the third domain of the ovomucoid from avian species, which is a Kazal-like domain. KTIL did not inhibit the enzymatic activity of various serine proteinases at pH = 7.2 or pH = 8.0, but partially inhibited the activity of trypsin at pH = 5.4, and the only toxic effect in mice observed after different in vivo tests was the induction of footpad edema. KTIL was not lethal when injected in mice or chickens. The presence of Kazal-type proteins and mRNA only in species of the genus Bothriechis suggests a genus recruitment event in the early-Middle Miocene, the estimated time of emergence of this clade.


Visual Interpretation of Kernel-Based Prediction Models.
Statistical models are frequently used to estimate molecular properties, e.g., to establish quantitative structure-activity and structure-property relationships. For such models, interpretability, knowledge of the domain of applicability, and an estimate of confidence in the predictions are essential. We develop and validate a method for the interpretation of kernel-based prediction models. As a consequence of interpretability, the method helps to assess the domain of applicability of a model, to judge the reliability of a prediction, and to determine relevant molecular features. Increased interpretability also facilitates the acceptance of such models. Our method is based on visualization: For each prediction, the most contributing training samples are computed and visualized. We quantitatively show the effectiveness of our approach by conducting a questionnaire study with 71 participants, resulting in significant improvements of the participants' ability to distinguish between correct and incorrect predictions of a Gaussian process model for Ames mutagenicity.


Roux-En-Y Gastric Bypass and Sleeve Gastrectomy Does Not Affect Food Preferences When Assessed by an Ad libitum Buffet Meal.
Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG) lead to a reduction in energy intake. It is uncertain whether this reduction is simply due to eating smaller portions or if surgery changes food preferences towards less energy-dense food. Previous results rely on verbal reports, which may be prone to recall bias and underestimation of especially unhealthy foods. Using an ad libitum buffet meal targeting direct behavior, we investigated if RYGB and SG surgery leads to changes in food preferences. In addition, we assessed food preferences by a picture display test to explore differences between a method relying on verbal report and a method assessing direct behavior. Forty-one subjects (BMI 45.0 ± 6.8 kg/m2) completed a visit pre- and 6 months post-RYGB (n = 31) and SG (n = 10). Mean BMI decreased with 11.7 ± 0.6 kg/m2 and total energy intake at the buffet meal with 54% (4491 ± 208 kJ vs. 2083 ± 208 kJ, P < 0.001), respectively. However, relative energy intake from the following food categories: high-fat, low-fat, sweet, savory, high-fat-savory, high-fat-sweet, low-fat-savory, and low-fat-sweet, as well as energy density did not change following surgery (all P ≥ 0.18). In contrast, the picture display test showed that food from the low-fat-savory group was chosen more often post-surgery (34 ± 8% vs. 65 ± 9%, P = 0.02). The reduction in energy intake after RYGB and SG surgery and the subsequent weight loss seems to be primarily related to a reduction in portion sizes and not by changes in food preferences towards less energy-dense foods. These results underline the necessity of investigating eating behavior by targeting direct behavior.


Commuting to school: are children who walk more physically active?
The journey to school is an opportunity for increasing children's daily physical activity. However, the contribution that active commuting to school makes to overall physical activity is unknown. This study used objective measurement to investigate the physical activity patterns of children by mode of travel to school. Primary-school children wore an accelerometer programmed to record minute-by-minute physical activity for 7 days and completed a brief questionnaire describing their usual travel to school. The total volume of physical activity and the time spent in activity of at least moderate intensity, as recorded by the accelerometer, was estimated for weekdays and the weekend, and groups of children were compared by mode of transport to school. Data were collected in May/June 2002. Of the 114 children (59 boys, 55 girls; aged 10.4+/-0.8 years) who took part in the study, those who walked to school (65%) were significantly more active than those who traveled by car (712.0+/-206.7 vs 629.9+/-207.2 accelerometer counts per minute, p=0.05). Analysis by gender indicated that the major differences in physical activity between travel groups were seen only in boys. Hourly activity patterns demonstrated that boys who walked to school were more active after school and throughout the evening than were car users. In boys, walking to school was associated with higher physical activity after school and during the evening. Active transport may contribute to a more physically active profile, at least for boys, supporting walk-to-school initiatives to increase children's physical activity.


Irregular repeat-accumulate codes for volume holographic memory systems.
We investigate the application of irregular repeat-accumulate (IRA) codes in volume holographic memory (VHM) systems. We introduce methodologies to design efficient IRA codes. We show that a judiciously designed IRA code for a typical VHM can be as good as the optimized irregular low-density-parity-check codes while having the additional advantage of lower encoding complexity. Moreover, we present a method to reduce the error-floor effect of the IRA codes in the VHM systems. This method explores the structure of the noise pattern in holographic memories. Finally, we explain why IRA codes are good candidates for the VHM systems.


Evaluation and correction for a 'training effect' in the cognitive assessment of older adults.
Repeated administration of psychometric instruments frequently results in a higher score on retesting, the so-called training effect. Yet, a training effect has been poorly considered in longitudinal studies of cognitive changes in older persons. We investigated the presence, magnitude and potential adjustments for training effect in the older participants of the Systolic Hypertension in the Elderly Program (SHEP). SHEP evaluated the cognitive status effects of a diuretic-based treatment of isolated systolic hypertension versus placebo. Changes in the short Comprehensive Assessment and Referral Evaluation (short-CARE) questionnaire score, from baseline through 4 years of follow-up, were assessed in 4,718 participants. In this study, we used two regression techniques to adjust data for the training effect. In both study groups, a training effect was evident as a progressive improvement in the short-CARE score throughout year 1. Thereafter, cognitive scores tended to deteriorate, more in the placebo than in the active treatment group (p = 0.055). When follow-up scores were adjusted based upon baseline data, the difference between the study groups reached statistical significance (p = 0.019), but the apparent overall trend towards deterioration in cognitive score was no longer observed. Adjustment of baseline data preserved this apparent temporal course, but did not improve the discrimination between the two study groups (p = 0.165). In SHEP, repeated cognitive assessments were likely biased by a training effect which could be only partially corrected by statistical techniques. Studies of changes in the cognitive status of older persons should be designed appropriately to estimate and minimize the consequences of a training effect in follow-up data.


HOXA13 promotes cancer cell growth and predicts poor survival of patients with esophageal squamous cell carcinoma.
Homeobox genes are known to be classic examples of the intimate relationship between embryogenesis and tumorigenesis. Here, we investigated whether inhibition of HOXA13, a member of the homeobox genes, was sufficient to affect the proliferation of esophageal cancer cells in vitro and in vivo, and studied the association between HOXA13 expression and survival of patients with esophageal squamous cell carcinoma (ESCC). HOXA13 expression was permanently knocked down using an RNA interference technique, and cell strain with stable knockdown of HOXA13 protein was established. Colony formation assay showed that the number of colonies in HOXA13 protein-deficient cells was significantly less than that of control cells (P < 0.01). Tumor growth in nude mice showed that the weight and volume of tumors from the HOXA13 knockdown cells was significantly less than that from the control cells (P < 0.01). Then, HOXA13 expression in ESCC specimens and paired noncancerous mucosa was detected by immunohistochemistry, and overexpression of HOXA13 was found to be more pronounced in ESCCs than paired noncancerous mucosa (P < 0.05). Furthermore, the association of HOXA13 expression and disease-free survival time was analyzed in 155 ESCC cases. The median survival time of patients expressing HOXA13 was significantly shorter than HOXA13-negative patients (P = 0.0006). Multivariate analysis indicated that tumor-node-metastasis (TNM) stage and HOXA13 expression were independent predictors of disease-free survival time of patients with ESCC. Our results showed that HOXA13 expression enhanced tumor growth in vitro and in vivo, and was a negative independent predictor of disease-free survival of patients with ESCC.


Factors associated with racial differences in child welfare investigative decision-making in Ontario, Canada.
Despite the substantial body of literature on racial disparities in child welfare involvement in the Unites States, there is relatively little research on such differences for Canadian children and families. This study begins to address this gap by examining decision-making among workers investigating Black and White families investigated for child protection concerns in Ontario, Canada. Using provincially representative data, the study assessed whether Black children were more likely than White children to be investigated by child welfare, if there was disparate decision-making by race throughout the investigation, and how the characteristics of Black and White children contribute to the decision to transfer to ongoing services. The results indicate that Black children were more likely to be investigated than White children, but there was little evidence to suggest that workers in Ontario child welfare agencies made the decision to substantiate, transfer to ongoing services, or place the child in out-of-home care based on race alone. Black and White children differed significantly with respect to child characteristics, characteristics of the investigation, caregiver risk factors, and socioeconomic circumstances. When adjusting for these characteristics, Black families had 33% greater odds (OR=1.33; 95% CI: 1.26, 1.40; p=<0.001) of being transferred to ongoing services compared to White families. Among Black families, the assessed quality of the parent-child relationship and severe economic hardship were the most significant and substantial contributors to the decision to provide child welfare services. Implications for practice, policy, and research are discussed.


Detection of infectious influenza virus in cough aerosols generated in a simulated patient examination room.
The potential for aerosol transmission of infectious influenza virus (ie, in healthcare facilities) is controversial. We constructed a simulated patient examination room that contained coughing and breathing manikins to determine whether coughed influenza was infectious and assessed the effectiveness of an N95 respirator and surgical mask in blocking transmission. National Institute for Occupational Safety and Health aerosol samplers collected size-fractionated aerosols for 60 minutes at the mouth of the breathing manikin, beside the mouth, and at 3 other locations in the room. Total recovered virus was quantitated by quantitative polymerase chain reaction and infectivity was determined by the viral plaque assay and an enhanced infectivity assay. Infectious influenza was recovered in all aerosol fractions (5.0% in >4 μm aerodynamic diameter, 75.5% in 1-4 μm, and 19.5% in <1 μm; n = 5). Tightly sealing a mask to the face blocked entry of 94.5% of total virus and 94.8% of infectious virus (n = 3). A tightly sealed respirator blocked 99.8% of total virus and 99.6% of infectious virus (n = 3). A poorly fitted respirator blocked 64.5% of total virus and 66.5% of infectious virus (n = 3). A mask documented to be loosely fitting by a PortaCount fit tester, to simulate how masks are worn by healthcare workers, blocked entry of 68.5% of total virus and 56.6% of infectious virus (n = 2). These results support a role for aerosol transmission and represent the first reported laboratory study of the efficacy of masks and respirators in blocking inhalation of influenza in aerosols. The results indicate that a poorly fitted respirator performs no better than a loosely fitting mask.


Prevalence and Characteristics of Autism Spectrum Disorder Among Children Aged 4 Years - Early Autism and Developmental Disabilities Monitoring Network, Seven Sites, United States, 2010, 2012, and 2014.
Autism spectrum disorder (ASD) is estimated to affect up to 3% of children in the United States. Public health surveillance for ASD among children aged 4 years provides information about trends in prevalence, characteristics of children with ASD, and progress made toward decreasing the age of identification of ASD so that evidence-based interventions can begin as early as possible. 2010, 2012, and 2014. The Early Autism and Developmental Disabilities Monitoring (Early ADDM) Network is an active surveillance system that provides biennial estimates of the prevalence and characteristics of ASD among children aged 4 years whose parents or guardians lived within designated sites. During surveillance years 2010, 2012, or 2014, data were collected in seven sites: Arizona, Colorado, Missouri, New Jersey, North Carolina, Utah, and Wisconsin. The Early ADDM Network is a subset of the broader ADDM Network (which included 13 total sites over the same period) that has been conducting ASD surveillance among children aged 8 years since 2000. Each Early ADDM site covers a smaller geographic area than the broader ADDM Network. Early ADDM ASD surveillance is conducted in two phases using the same methods and project staff members as the ADDM Network. The first phase consists of reviewing and abstracting data from children's records, including comprehensive evaluations performed by community professionals. Sources for these evaluations include general pediatric health clinics and specialized programs for children with developmental disabilities. In addition, special education records (for children aged ≥3 years) were reviewed for Arizona, Colorado, New Jersey, North Carolina, and Utah, and early intervention records (for children aged 0 to <3 years) were reviewed for New Jersey, North Carolina, Utah, and Wisconsin; in Wisconsin, early intervention records were reviewed for 2014 only. The second phase involves a review of the abstracted evaluations by trained clinicians using a standardized case definition and method. A child is considered to meet the surveillance case definition for ASD if one or more comprehensive evaluations of that child completed by a qualified professional describes behaviors consistent with the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision (DSM-IV-TR) diagnostic criteria for any of the following conditions: autistic disorder, pervasive developmental disorder-not otherwise specified (PDD-NOS, including atypical autism), or Asperger disorder (2010, 2012, and 2014). For 2014 only, prevalence estimates based on surveillance case definitions according to DSM-IV-TR and the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) were compared. This report provides estimates of overall ASD prevalence and prevalence by sex and race/ethnicity; characteristics of children aged 4 years with ASD, including age at first developmental evaluation, age at ASD diagnosis, and cognitive function; and trends in ASD prevalence and characteristics among Early ADDM sites with data for all 3 surveillance years (2010, 2012, and 2014), including comparisons with children aged 8 years living in the same geographic area. Analyses of time trends in ASD prevalence are restricted to the three sites that contributed data for all 3 surveillance years with consistent data sources (Arizona, Missouri, and New Jersey). The overall ASD prevalence was 13.4 per 1,000 children aged 4 years in 2010, 15.3 in 2012, and 17.0 in 2014 for Early ADDM sites with data for the specific years. ASD prevalence was determined using a surveillance case definition based on DSM-IV-TR. Within each surveillance year, ASD prevalence among children aged 4 years varied across surveillance sites and was lowest each year for Missouri (8.5, 8.1, and 9.6 per 1,000, for 2010, 2012, and 2014, respectively) and highest each year for New Jersey (19.7, 22.1, and 28.4 per 1,000, for the same years, respectively). Aggregated prevalence estimates were higher for sites that reviewed education and health care records than for sites that reviewed only health care records. Among all participating sites and years, ASD prevalence among children aged 4 years was consistently higher among boys than girls; prevalence ratios ranged from 2.6 (Arizona and Wisconsin in 2010) to 5.2 boys per one girl (Colorado in 2014). In 2010, ASD prevalence was higher among non-Hispanic white children than among Hispanic children in Arizona and non-Hispanic black children in Missouri; no other differences were observed by race/ethnicity. Among four sites with ≥60% data on cognitive test scores (Arizona, New Jersey, North Carolina, and Utah), the frequency of co-occurring intellectual disabilities was significantly higher among children aged 4 years than among those aged 8 years for each site in each surveillance year except Arizona in 2010. The percentage of children with ASD who had a first evaluation by age 36 months ranged from 48.8% in Missouri in 2012 to 88.9% in Wisconsin in 2014. The percentage of children with a previous ASD diagnosis from a community provider varied by site, ranging from 43.0% for Arizona in 2012 to 86.5% for Missouri in 2012. The median age at earliest known ASD diagnosis varied from 28 months in North Carolina in 2014 to 39.0 months in Missouri and Wisconsin in 2012. In 2014, the ASD prevalence based on the DSM-IV-TR case definition was 20% higher than the prevalence based on the DSM-5 (17.0 versus 14.1 per 1,000, respectively). Trends in ASD prevalence and characteristics among children aged 4 years during the study period were assessed for the three sites with data for all 3 years and consistent data sources (Arizona, Missouri, and New Jersey) using the DSM-IV-TR case definition; prevalence was higher in 2014 than in 2010 among children aged 4 years in New Jersey and was stable in Arizona and Missouri. In Missouri, ASD prevalence was higher among children aged 8 years than among children aged 4 years. The percentage of children with ASD who had a comprehensive evaluation by age 36 months was stable in Arizona and Missouri and decreased in New Jersey. In the three sites, no change occurred in the age at earliest known ASD diagnosis during 2010-2014. The findings suggest that ASD prevalence among children aged 4 years was higher in 2014 than in 2010 in one site and remained stable in others. Among children with ASD, the frequency of cognitive impairment was higher among children aged 4 years than among those aged 8 years and suggests that surveillance at age 4 years might more often include children with more severe symptoms or those with co-occurring conditions such as intellectual disability. In the sites with data for all years and consistent data sources, no change in the age at earliest known ASD diagnosis was found, and children received their first developmental evaluation at the same or a later age in 2014 compared with 2010. Delays in the initiation of a first developmental evaluation might adversely affect children by delaying access to treatment and special services that can improve outcomes for children with ASD. Efforts to increase awareness of ASD and improve the identification of ASD by community providers can facilitate early diagnosis of children with ASD. Heterogeneity of results across sites suggests that community-level differences in evaluation and diagnostic services as well as access to data sources might affect estimates of ASD prevalence and age of identification. Continuing improvements in providing developmental evaluations to children as soon as developmental concerns are identified might result in earlier ASD diagnoses and earlier receipt of services, which might improve developmental outcomes.


Relationships between biomarkers in aging and dementia.
PET imaging using [(18)F]fluorodeoxyglucose (FDG) and [(11)C]Pittsburgh compound B (PIB) have been proposed as biomarkers of Alzheimer disease (AD), as have CSF measures of the 42 amino acid beta-amyloid protein (Abeta(1-42)) and total and phosphorylated tau (t-tau and p-tau). Relationships between biomarkers and with disease severity are incompletely understood. Ten subjects with AD, 11 control subjects, and 34 subjects with mild cognitive impairment from the Alzheimer's Disease Neuroimaging Initiative underwent clinical evaluation; CSF measurement of Abeta(1-42), t-tau, and p-tau; and PIB-PET and FDG-PET scanning. Data were analyzed using continuous regression and dichotomous outcomes with subjects classified as "positive" or "negative" for AD based on cutoffs established in patients with AD and controls from other cohorts. Dichotomous categorization showed substantial agreement between PIB-PET and CSF Abeta(1-42) measures (91% agreement, kappa = 0.74), modest agreement between PIB-PET and p-tau (76% agreement, kappa = 0.50), and minimal agreement for other comparisons (kappa <0.3). Mini-Mental State Examination score was significantly correlated with FDG-PET but not with PIB-PET or CSF Abeta(1-42). Regression models adjusted for diagnosis showed that PIB-PET was significantly correlated with Abeta(1-42), t-tau, and p-tau(181p), whereas FDG-PET was correlated only with Abeta(1-42). PET and CSF biomarkers of Abeta agree with one another but are not related to cognitive impairment. [(18)F]fluorodeoxyglucose-PET is modestly related to other biomarkers but is better related to cognition. Different biomarkers for Alzheimer disease provide different information from one another that is likely to be complementary.


Controllable entanglement preparations between atoms in spatially-separated cavities via quantum Zeno dynamics.
By using quantum Zeno dynamics, we propose a controllable approach to deterministically generate tripartite GHZ states for three atoms trapped in spatially separated cavities. The nearest-neighbored cavities are connected via optical fibers and the atoms trapped in two ends are tunably driven. The generation of the GHZ state can be implemented by only one step manipulation, and the EPR entanglement between the atoms in two ends can be further realized deterministically by Von Neumann measurement on the middle atom. Note that the duration of the quantum Zeno dynamics is controllable by switching on/off the applied external classical drivings and the desirable tripartite GHZ state will no longer evolve once it is generated. The robustness of the proposal is numerically demonstrated by considering various decoherence factors, including atomic spontaneous emissions, cavity decays and fiber photon leakages, etc. Our proposal can be directly generalized to generate multipartite entanglement by still driving the atoms in two ends.


The Effect of Yoga and Peer Support Interventions on the Quality of Life of Women with Diabetes: Results of a Randomized Controlled Trial.
This was an interventional study to understand the effect of two low-cost interventions; yoga and peer support on the quality of life (QOL) of women with type 2 diabetes. An open label parallel three-armed randomized control trial was conducted among 124 recruited women with diabetes for 3 months. Block randomization with a block length of six was carried out. In the yoga arm, sessions by an instructor, consisting of a group of postures coordinated with breathing were conducted for an hour, 2 days a week. In the peer support arm, each peer mentor after training visited 13-14 women with diabetes every week followed by a phone call. The meeting was about applying disease management plans in daily life. At the beginning and end of the study, QOL was assessed by the translated, validated World Health Organization QOL-BREF in four domains physical, psychological, social, and environmental domains. The majority (96%) of the study participants perceived the peer support and yoga intervention to be beneficial. Paired t-test revealed significant increases in the social and environmental domain in the peer group and in the environmental domain in the yoga group, though this disappeared in the between-group comparison perhaps due to poor glycemic control (hemoglobin A1c varied from 9.4 to 9.6) and the short duration of 3 months of the study. Peer support and yoga improved perceptions of QOL though its impact on scores was not significant due to a short period of study among women with poor glycemic control.


Activation of Toll-Like Receptors Differentially Modulates Inflammation in the Human Reproductive Tract: Preliminary Findings.
The female reproductive tract (FRT) is the main site of entry of sexually transmitted infections (STIs). Toll-like receptors (TLRs) that recognize pathogenic motifs are widely expressed in the FRT. TLR stimulation induces immune activation and local production of inflammatory mediators. In the FRT, this response should also be compatible with reproductive functions and symbiosis with host microbiota. With a view to develop efficient mucosal vaccines to prevent STI acquisition, the role of TLR ligands in the FRT needs to be explored. We have therefore investigated the cytokine profiles of the different compartments of the FRT (vagina, endocervix, ectocervix, and uterus) before and after stimulation of mononuclear cells from human tissue specimens. The comparison with PBMCs allowed us to highlight the FRT specificities. We first characterized the main immune cell populations in each compartment and observed that their distribution was different through the compartments. The CD45+ cells represented a maximum of 11% in the FRT in contrast to 96% in PBMCs. We identified two main populations among the CD45+ cells in the four compartments of the FRT: CD3+ T cells (CD4+ and CD8+) and CD14+ APCs. B cell populations (CD19+) were much less frequent than T cells in all the FRT regions and were equally distributed. NK CD56+ cells were detected in all compartments and were more abundant in the uterus. Stimulation of the mononuclear cells was then performed with TLR agonists: R848 for TLR7/8, Poly I:C for TLR3, LPS for TLR4 and ODN CpG for TLR9. Cytokine levels in unstimulated cultures of cells isolated from all FRT compartments were higher than in cultures of unstimulated PBMCs. In contrast, after stimulation with TLR agonists, cytokine responses induced by TLR agonists were moderate in the FRT and significantly lower than in PBMCs. These responses were varied with different TLR ligands and FRT compartments. The cytokine profile induced by TLR activation in the FRT supports the role of these tissues in genital anti-microbial immunity and in the control of inflammation while allowing maintenance of its reproductive function.


Post-traumatic psychiatric disturbances: patterns and predictors of outcome.
A prospective follow-up study of 60 randomly selected cases of closed adult civilian head injuries was conducted for three months from the time of head injury to assess the frequency, patterns, and factors related to post-traumatic psychiatric disturbances. Eighty per cent of the cases had a neuropsychiatric disturbance as assessed at 1 1/2 months. The commonest was post-concussional syndrome (43 per cent). The extent of social dysfunction was directly related to the severity of head injury. However, the total number of symptoms (largely subjective) correlated highly with pre-traumatic neuroticism. The inter-relatedness of organic and personality factors in the post-traumatic syndrome, and their predictive value, are discussed.


Schistosoma mansoni specimens first described by Pirajá da Silva in Brazil (1908) re-examined by confocal laser scanning microscopy.
Pirajá da Silva made a seminal contribution to helminthology by demonstrating both schistosome eggs in feces of patients from the State of Bahia and the morphology of Schistosoma mansoni adult worms. In this study, a microscopic investigation of the whole-mounts deposited at the Helminthological Collection of the Oswaldo Cruz Institute is presented. Confocal laser scanning microscopy was used as the main investigation technique. At the anterior end of the adult male, suckers with well-developed musculature and germinative cells inside the testicular lobes were observed, as well as spines located in the mid region of the male gynecophoric canal. Tegumental tubercles and transversal and longitudinal muscular bundles were observed at the dorsal surface. The female reproductive system presented a uterus lacking eggs and an elongated ovary with germinative cells. The vitellaria were restricted to the extreme posterior end of each female connected to a short vitelline duct. The results reported in this study demonstrate that the characteristic studied here are similar to those previously reported, using fresh worms. Moreover, this study also highlights the importance of deposits of specimens in helminthological collections, which further permit revisiting whole-mounts in such institutions.


Synovial macrophage-osteoclast differentiation in inflammatory arthritis.
Pathological bone resorption (marginal erosions and juxta-articular osteoporosis) by osteoclasts commonly occurs in rheumatoid arthritis (RA). To define the nature of the mononuclear precursor cells from which osteoclasts are formed in inflamed synovial tissues and to determine the cellular and humoral factors which influence osteoclast differentiation. Macrophage (CD14+), non-macrophage (CD14-), and unsorted (CD14+/CD14-) synovial cell populations from RA and inflammatory/non-inflammatory osteoarthritis (OA) synovium were cultured in the presence of receptor activator for nuclear factor kappaB ligand (RANKL) and monocyte-colony stimulating factor (M-CSF; in the presence/absence of prostaglandin E(2) (PGE(2)), interleukin 1beta (IL1beta), tumour necrosis factor alpha (TNFalpha), and IL6). Osteoclast differentiation was assessed by expression of tartrate resistant acid phosphatase (TRAP), vitronectin receptor (VNR), and lacunar resorption. TRAP+ and VNR+ multinucleated cells capable of lacunar resorption were only formed in cultures of CD14+-containing synovial cell populations (that is, CD14+ and CD14+/CD14- cells). No difference in the extent of osteoclast formation was noted in cultures of CD14+ cells isolated from RA, inflammatory OA, and non-inflammatory OA synovium. However, more TRAP+/VNR+ cells and more lacunar resorption was noted in CD14+/CD14- cells from RA and inflammatory OA synovial tissues. The addition of PGE(2), IL1beta, TNFalpha, and IL6 did not increase RANKL/M-CSF-induced osteoclast formation and lacunar resorption of both CD14+/CD14- and CD14+ synovial cell populations. Osteoclast precursors in synovial tissues are CD14+ monocyte/macrophages. The increase in osteoclast formation in cultures of CD14+/CD14- compared with CD14+ synovial cells in RA and inflammatory OA points to a role for CD14- cells in promoting osteoclast differentiation and bone resorption in inflamed synovial tissues by a mechanism which does not involve a direct effect of proinflammatory cytokines/prostaglandins on RANKL-induced macrophage-osteoclast differentiation.


Confusing Relative Risk with Absolute Risk Is Associated with More Enthusiastic Beliefs about the Value of Cancer Screening.
Reviews of how data are presented in medical literature document that the benefit from an intervention is often exaggerated relative to the harm (e.g., relative risk for benefit and absolute risk for harm). Such mismatched presentations may create unwarranted enthusiasm, especially among those who misinterpret the statistics presented. The objective was to determine whether misinterpretation of risk data predicts enthusiasm for cancer screening. The authors administered a survey with 14 items assessing beliefs about cancer screening and 6 items measuring data interpretation ability. Multiple linear regression was used to evaluate the association between data interpretation and enthusiasm for cancer screening, with adjustment for gender and year graduated from medical school. Eighty-eight of 139 physicians at a state-wide professional meeting returned completed surveys (63% response rate). Lower data interpretation scores were associated with higher enthusiasm for cancer screening scores (P = 0.004) in the adjusted primary analysis. Confusing relative risk with absolute risk appeared to drive the overall association. Biased presentations of risk data could affect general beliefs about the value of cancer screening, especially among physicians who uncritically accept mismatched presentations of data.


The association between anti-Müllerian hormone and IVF-ICSI outcome in poor responder patients performing long protocol.
Ovarian reserve reflects the capacity of the ovaries for a successful pregnancy. Anti-Müllerian hormone (AMH) could be a useful marker to predict ovarian reserve and to adjust controlled ovarian stimulation. The aim of this study was to assess the relationship between AMH and intracytoplasmic sperm injection-in vitro fertilization (IVF-ICSI) outcome in poor responder women. This study was conducted prospectively for a period of 12 months. Inclusion criteria were FSH value > 15 iu/l or antral follicle number < 4, on the 2nd day of cycle. All patients underwent GnRH agonist stimulation with long protocol. Serum AMH levels were measured in the treatment cycle just before the stimulation. After the treatment, patients who were pregnant formed the study group and patients who were not pregnant formed the control group. Serum AMH level was the main outcome measure. The study and control group consisted of 34 and 70 patients, respectively. No significant difference was found in duration of infertility, antral follicular count, basal E2 and FSH levels. The mean serum AMH level was significantly higher in study group (p = 0.005). The retrieved oocyte number, metaphase 2 oocyte number, and fertilization rate were also significantly higher in the study group. Evaluation of serum AMH seems to be a useful marker to predict IVF-ICSI outcome in poor responder patients.


Development of a quasi-phase-matched, second-harmonic generation periodically poled lithium niobate waveguide with an integrated electro-optical modulator.
A novel type of waveguide quasi-phase-matched device with output electro-optical (EO) modulation is proposed and demonstrated. The second-harmonic generated output can be modulated with a high extinction ratio by integration of dual EO phase modulators on a periodically poled lithium niobate waveguide. Blue and green coherent light with EO modulation was demonstrated, and wavelength dispersion of r33 is discussed.


Reducing the need for central dual-energy X-ray absorptiometry in postmenopausal women: efficacy of a clinical algorithm including peripheral densitometry.
We evaluated the efficacy of a triage approach based on a combination of osteoporosis risk-assessment tools plus peripheral densitometry to identify low bone density accurately enough to be useful for clinical decision making in postmenopausal women. We conducted a cross-sectional diagnostic study in postmenopausal Caucasian women from primary and tertiary care. All women underwent dual-energy X-ray absorptiometric (DXA) measurement at the hip and lumbar spine and were categorized as osteoporotic or not. Additionally, patients had a nondominant heel densitometry performed with a PIXI densitometer. Four osteoporosis risk scores were tested: SCORE, ORAI, OST, and OSIRIS. All measurements were cross-blinded. We estimated the area under the curve (AUC) to predict the DXA results of 16 combinations of PIXI plus risk scores. A formula including the best combination was derived from a regression model and its predictability estimated. We included 505 women, in whom the prevalence of osteoporosis was 20 %, similar in both settings. The best algorithm was a combination of PIXI + OST + SCORE with an AUC of 0.826 (95 % CI 0.782-0.869). The proposed formula is Risk = (-12) × [PIXI + (-5)] × [OST + (-2)] × SCORE and showed little bias in the estimation (0.0016). If the formula had been implemented and the intermediate risk cutoff set at -5 to 20, the system would have saved <euro>4,606.34 in the study year. The formula proposed, derived from previously validated risk scores plus a peripheral bone density measurement, can be used reliably in primary care to avoid unnecessary central DXA measurements in postmenopausal women.


Population bottlenecks in multicomponent viruses: first forays into the uncharted territory of genome-formula drift.
Multicomponent viral systems face specific challenges when enduring population bottlenecks. These systems can lose coding information due to the lack of co-encapsidation of all the genetic information, at least in a proportion of the capsids in a population. Moreover, bottlenecks can also impact one of the main potential advantages of multicomponent systems: the regulation of gene expression through changes in gene copy frequencies at the population level. How these systems cope with population bottlenecks is far from being clear. Here, two non-exclusive scenarios are described. In the first scenario, population bottlenecks during host infection allow for the isolation of within-host populations with different gene frequencies, leaving the door opened for the selection of populations with adaptive gene frequencies. The second scenario postulates that viruses could influence bottleneck size, at least at certain steps of their life cycle, to limit random changes in gene frequencies. Examples of viral mechanism impacting bottleneck size at cell infection are available and, intriguingly, they can lead to either increases or reductions in bottleneck size. This situation opens the way for putative trade-offs on both gene frequencies and bottleneck sizes that could differ among multicomponent systems.


Triggering of cardiovascular hospital admissions by fine particle concentrations in New York state: Before, during, and after implementation of multiple environmental policies and a recession.
Previous studies reported triggering of acute cardiovascular events by short-term increasedPM2.5 concentrations. From 2007 to 2013, national and New York state air quality policies and economic influences resulted in reduced concentrations of PM2.5 and other pollutants across the state. We estimated the rate of cardiovascular hospital admissions associated with increased PM2.5 concentrations in the previous 1-7 days, and evaluated whether they differed before (2005-2007), during (2008-2013), and after these concentration changes (2014-2016). Using the Statewide Planning and Research Cooperative System (SPARCS) database, we retained all hospital admissions with a primary diagnosis of nine cardiovascular disease (CVD) subtypes, for residents living within 15 miles of PM2.5 monitoring sites in Buffalo, Rochester, Albany, Queens, Bronx, and Manhattan from 2005 to 2016 (N = 1,922,918). We used a case-crossover design and conditional logistic regression to estimate the admission rate for total CVD, and nine specific subtypes, associated with increased PM2.5 concentrations. Interquartile range (IQR) increases in PM2.5 on the same and previous 6 days were associated with 0.6%-1.2% increases in CVD admission rate (2005-2016). There were similar patterns for cardiac arrhythmia, ischemic stroke, congestive heart failure, ischemic heart disease (IHD), and myocardial infarction (MI). Ambient PM2.5 concentrations and annual total CVD admission rates decreased across the period. However, the excess rate of IHD admissions associated with each IQR increase in PM2.5 in previous 2 days was larger in the after period (2.8%; 95%CI = 1.5%-4.0%) than in the during (0.6%; 95%CI = 0.0%-1.2%) or before periods (0.8%; 95%CI = 0.2%-1.3%), with similar patterns for total CVD and MI, but not other subtypes. While pollutant concentrations and CVD admission rates decreased after emission changes, the same PM2.5 mass was associated with a higher rate of ischemic heart disease events. Future work should confirm these findings in another population, and investigate whether specific PM components and/or sources trigger IHD events.


Two modes of microsatellite instability in human cancer: differential connection of defective DNA mismatch repair to dinucleotide repeat instability.
Microsatellite instability (MSI) is associated with defective DNA mismatch repair in various human malignancies. Using a unique fluorescent technique, we have observed two distinct modes of dinucleotide microsatellite alterations in human colorectal cancer. Type A alterations are defined as length changes of < or =6 bp. Type B changes are more drastic and involve modifications of > or =8 bp. We show here that defective mismatch repair is necessary and sufficient for Type A changes. These changes were observed in cell lines and in tumours from mismatch repair gene-knockout mice. No Type B instability was seen in these cells or tumours. In a panel of human colorectal tumours, both Type A MSI and Type B instability were observed. Both types of MSI were associated with hMSH2 or hMLH1 mismatch repair gene alterations. Intriguingly, p53 mutations, which are generally regarded as uncommon in human tumours of the MSI+ phenotype, were frequently associated with Type A instability, whereas none was found in tumours with Type B instability, reflecting the prevailing viewpoint. Inspection of published data reveals that the microsatellite instability that has been observed in various malignancies, including those associated with Hereditary Non-Polyposis Colorectal Cancer (HNPCC), is predominantly Type B. Our findings indicate that Type B instability is not a simple reflection of a repair defect. We suggest that there are at least two qualitatively distinct modes of dinucleotide MSI in human colorectal cancer, and that different molecular mechanisms may underlie these modes of MSI. The relationship between MSI and defective mismatch repair may be more complex than hitherto suspected.


Evaluation of Vestibular Evoked Myogenic Potentials (VEMP) Individuals with Tinnitus and Normal Hearing.
The aim the present study is to evaluate ocular and cervical Vestibular Evoked Myogenic Potentials (VEMPs) of adult individuals with and without tinnitus who have normal hearing. Thirty one patients who have normal hearing, complaining about unilateral or bilateral subjective tinnitus and 30 volunteers who without tinnitus and vestibular complains were enrolled into the present study. Following examination by of Ear Nose Throat (ENT) physician, Tinnitus Disability Questionnaire (TDQ), pure tone audiometry (125-16.000 Hz) speech tests, oVEMP and cVEMP tests were applied to all participants. Fourteen individuals with normal hearing and tinnitus were male (44%) and 17 (56%) were female with an age average of 35.8 ± 10.2.30 years; the control group consisted of 16 males (53%) and 14 females (47%) with an age average of 37.5 ± 12 years. Two individuals of the tinnitus group had bilateral tinnitus and 29 individuals had unilateral tinnitus. A statistically significant difference in individuals without tinnitus and tinnitus must be normal at work between test answers that are not available 125-16000 Hz range Air Conduction (AC) hearing thresholds, speech tests, cVEMP and oVEMP responses. Tinnitus may appear due to many reasons. Vestibular system is one of the conditions that can cause tinnitus. According to the findings obtained from adult individuals with normal hearing, the vestibular system does not cause tinnitus.


A novel semiautomated atherosclerotic plaque characterization method using grayscale intravascular ultrasound images: comparison with virtual histology.
Intravascular ultrasound (IVUS) virtual histology (VH-IVUS) is a new technique, which provides automated plaque characterization in IVUS frames, using the ultrasound backscattered RF-signals. However, its computation can only be performed once per cardiac cycle (ECG-gated technique), which significantly decreases the number of characterized IVUS frames. Also atherosclerotic plaques in images that have been acquired by machines, which are not equipped with the VH software, cannot be characterized. To address these limitations, we have developed a plaque characterization technique that can be applied in grayscale IVUS images. Our semiautomated method is based on a three-step approach. In the first step, the plaque area [region of interest (ROI)] is detected semiautomatically. In the second step, a set of features is extracted for each pixel of the ROI and in the third step, a random forest classifier is used to classify these pixels into four classes: dense calcium, necrotic core, fibrotic tissue, and fibro-fatty tissue. In order to train and validate our method, we used 300 IVUS frames acquired from virtual histology examinations from ten patients. The overall accuracy of the proposed method was 85.65% suggesting that our approach is reliable and may be further investigated in the clinical and research arena.


Subsequent Injury Study (SInS): Improving outcomes for injured New Zealanders.
Subsequent injury (SI) is a major contributor to disability and costs for individuals and society. To identify modifiable risk factors predictive of SI and SI health and disability outcomes and costs. To (1) describe the nature of SIs reported to New Zealand's no-fault injury insurer (the Accident Compensation Corporation (ACC)); (2) identify characteristics of people underaccessing ACC for SI; (3) determine factors predicting or protecting against SI; and (4) investigate outcomes for individuals, and costs to society, in relation to SI. Prospective cohort study. Previously collected data will be linked including data from interviews undertaken as part of the earlier Prospective Outcomes of Injury Study (POIS), ACC electronic data and national hospitalisation data about SI. POIS participants (N=2856, including 566 Māori) were recruited via ACC's injury register following an injury serious enough to warrant compensation entitlements. We will examine SI over the following 24 months for these participants using descriptive and inferential statistics including multivariable generalised linear models and Cox's proportional hazards regression. Subsequent Injury Study (SInS) will deliver information about the risks, protective factors and outcomes related to SI for New Zealanders. As a result of sourcing injury data from New Zealand's 'all injury' insurer ACC, SInS includes people who have been hospitalised and not hospitalised for injury. Consequently, SInS will provide insights that are novel internationally as other studies are usually confined to examining trauma registries, specific injuries or injured workers who are covered by a workplace insurer rather than a 'real-world' injury population.


Minichromosome Maintenance Protein 7 is a potential therapeutic target in human cancer and a novel prognostic marker of non-small cell lung cancer.
The research emphasis in anti-cancer drug discovery has always been to search for a drug with the greatest antitumor potential but fewest side effects. This can only be achieved if the drug used is against a specific target located in the tumor cells. In this study, we evaluated Minichromosome Maintenance Protein 7 (MCM7) as a novel therapeutic target in cancer. Immunohistochemical analysis showed that MCM7 was positively stained in 196 of 331 non-small cell lung cancer (NSCLC), 21 of 29 bladder tumor and 25 of 70 liver tumor cases whereas no significant staining was observed in various normal tissues. We also found an elevated expression of MCM7 to be associated with poor prognosis for patients with NSCLC (P = 0.0055). qRT-PCR revealed a higher expression of MCM7 in clinical bladder cancer tissues than in corresponding non-neoplastic tissues (P < 0.0001), and we confirmed that a wide range of cancers also overexpressed MCM7 by cDNA microarray analysis. Suppression of MCM7 using specific siRNAs inhibited incorporation of BrdU in lung and bladder cancer cells overexpressing MCM7, and suppressed the growth of those cells more efficiently than that of normal cell strains expressing lower levels of MCM7. Since MCM7 expression was generally low in a number of normal tissues we examined, MCM7 has the characteristics of an ideal candidate for molecular targeted cancer therapy in various tumors and also as a good prognostic biomarker for NSCLC patients.


Assessment of pulmonary lesions with 18F-fluorodeoxyglucose positron imaging using coincidence mode gamma cameras.
Accurate assessment of lung carcinoma remains a significant clinical problem, often leading to surgical procedures without curative potential. PET with 18F-fluorodeoxyglucose (FDG) has shown promise in differentiating benign from malignant lesions and in staging the extent of disease, resulting in improved treatment at a significant cost savings. This multicenter prospective study used dual-detector coincidence imaging with FDG to categorize pulmonary lesions as benign or malignant. The goal of this study was to determine the sensitivity and specificity of dual-detector coincidence imaging of FDG in patients with pulmonary lesions who were scheduled to have a diagnostic procedure for histopathologic confirmation. A total of 96 patients with pulmonary lesions with a lesion size ranging from 1 to 7 cm with a mean of 3.44 cm based on their chest radiograph or CT scan were studied using FDG scans with a dual-detector coincidence detection system. An additional 24 patients were entered as control subjects. The studies of 120 subjects were interpreted in random order by three physicians experienced in the use of FDG in patients with lung cancer. Surgical pathology was used as the standard for identifying malignant lesions. There was 94% agreement between the readers in the independent interpretation of the FDG studies. In the 96 patients with pulmonary lesions, FDG studies were 97% sensitive and 80% specific in identifying proven malignant lesions. The results of this prospective study provide evidence that dual-detector coincidence imaging with FDG provides an accurate, sensitive and specific means of diagnosing malignancy in patients with pulmonary lesions.


Elevated Genetic Diversity in an F2:6 Population of Quinoa (Chenopodium quinoa) Developed through an Inter-ecotype Cross.
Quinoa (Chenopodium quinoa) is a seed crop of the Andean highlands and Araucanian coastal regions of South America that has recently expanded in use and production beyond its native range. This is largely due to its superb nutritional value, consisting of protein that is rich in essential amino acids along with vitamins and minerals. Quinoa also presents a remarkable degree of tolerance to saline conditions, drought, and frost. The present study involved 72 F2:6 recombinant-inbred lines and parents developed through hybridization between highland (0654) and coastal (NL-6) germplasm groups. The purpose was to characterize the quinoa germplasm developed, to assess the discriminating potential of 21 agro-morpho-phenological traits, and to evaluate the extent of genetic variability recovered through selfing. A vast amount of genetic variation was detected among the 72 lines evaluated for quantitative and qualitative traits. Impressive transgressive segregation was measured for seed yield (22.42 g/plant), while plant height and maturity had higher heritabilities (73 and 89%, respectively). Other notable characters segregating in the population included panicle and stem color, panicle form, and resistance to downy mildew. In the Principal Component analysis, the first axis explained 74% of the total variation and was correlated to plant height, panicle size, stem diameter, biomass, mildew reaction, maturation, and seed yield; those traits are relevant discriminatory characters. Yield correlated positively with panicle length and biomass. Unweighted Pair Group Method with Arithmetic Mean-based cluster analysis identified three groups: one consisting of late, mildew-resistant, high-yielding lines; one having semi-late lines with intermediate yield and mildew susceptibility; and a third cluster consisting of early to semi-late accessions with low yield and mildew susceptibility. This study highlighted the extended diversity regenerated among the 72 accessions and helped to identify potentially adapted quinoa genotypes for production in the Moroccan coastal environment.


Factors predicting the health status of caregivers of stroke survivors: A cross-sectional study.
In this cross-sectional study, we aimed to determine factors influencing the health status of caregivers of stroke survivors. A total of 126 caregivers of stroke survivors were recruited from three outpatient clinics in Thai Nguyen National General Hospital, Vietnam, from November 2016 to March 2017. Data were collected through six instruments: a demographic questionnaire, the Modified Barthel Index, the Zarit Burden Interview Scale, the Multidimensional Scale of Perceived Social Support, the Family Caregiver Conflict Scale, and the Short Form-36 Health Survey. Stepwise multiple regression was employed to analyze the data. Caregiver burden, patient's functional status, caregiver's age, and social support together explained 80.3% of the variations in health status of caregivers of stroke survivors. Caregiver burden was the strongest predictor of health status of these caregivers. Based on the findings, nurses should take caregiver's age, functional status of stroke survivors, caregiver burden, and social support into consideration when preparing family caregivers to provide care for stroke survivors. To reduce perceived caregiver burden, family support interventions should be embraced to enhance health status of the caregivers of stroke survivors.


Engineering a high throughput axon injury system.
Several key biological mechanisms of traumatic injury to axons have been elucidated using in vitro stretch injury models. These models, however, are based on the experimentation of single cultures keeping productivity slow. Indeed, low yield has hindered important and well-founded investigations requiring high throughput methods such as proteomic analyses. To meet this need, we engineered a multi-well high throughput injury device to accelerate and accommodate the next generation of traumatic brain injury research. This modular system stretch injures neuronal cultures in either a 24-well culture plate format or 6 individual wells simultaneously. Custom software control allows the user to accurately program the pressure pulse parameters to achieve the desired substrate deformation and injury parameters. Analysis of the pressure waveforms showed that peak pressure was linearly related to input pressure and valve open times and that the 6- and 24-well modules displayed rise times, peak pressures, and decays with extremely small standard deviations. Data also confirmed that the pressure pulse was distributed evenly throughout the pressure chambers and therefore to each injury well. Importantly, the relationship between substrate deformation and applied pressure was consistent among the multiple wells and displayed a predictable linear behavior in each module. These data confirm that this multi-well system performs as well as currently used stretch injury devices and can undertake high throughput studies that are needed across the field of neurotrauma research.


Site specific phosphorylation of insulin-like growth factor binding protein-1 (IGFBP-1) for evaluating clinical relevancy in fetal growth restriction.
Fetal growth restriction (FGR) is a leading cause of fetal and neonatal morbidity and mortality. Insulin-like growth factor binding protein-1 (IGFBP-1) is one of the major insulin-like growth factor (IGF) binding proteins involved in fetal growth and development. Our recent data shows that phosphorylation of IGFBP-1 carries both functional and biological relevance in FGR. Considering that IGFBP-1 phosphorylation can be valuable in diagnostics, we examined strategies to enrich IGFBP-1 so that its phosphorylation sites could be assessed by mass spectrometry (MS). Using <1 mL of human amniotic fluid, widely employed immunoprecipitation with IGFBP-1 monoclonal antibody (Mab 6303) coenriched IgGs that interfered with MS. Covalent coupling of Mab 6303 with Seize immunoprecipitation resin (Pierce) mitigated this drawback. However, LC-MS/MS analysis with the titanium dioxide (TiO(2)) enriched IGFBP-1 phosphopeptides in the immunoprecipitated samples revealed pSer101 and pSer119, but not pSer169 nor pSer98 of the previously identified phosphorylation sites. The alternative, ZOOM isoelectric focusing (IEF) (Invitrogen) rendered low-IGFBP-1 recovery with overlapping albumin. Subsequently, depletion of albumin using Affi-GelBlue gel (Bio-Rad) maximized IGFBP-1 yield. ELISA estimation showed approximately 8.5% residual albumin (3.73 x 10(5) +/- 2.35 x 10(5) ng/mL), whereas up to approximately 68% IGFBP-1 was recovered (1.36 x 10(3) +/- 0.174 x 10(3) microg/L, IEMA). LC-MS/MS analysis with the albumin depleted samples detected all four expected phosphorylation sites. Additionally, LC-MS analysis semiquantitatively indicated much reduced phosphopeptide peak intensities, approximately 20-fold with pSer169 and approximately 10-fold lower with pSer98 sites as compared to pSer101. With the use of our depletion strategy, this study offers a novel simple proteomic approach to enrich IGFBP-1 for identification of site-specific changes in IGFBP-1 phosphorylation. This strategy will be vital in performing differential IGFBP-1 phosphorylation profiling clinically, to help establish its link with FGR and develop diagnostic assays, as well as elucidating novel mechanisms potentially involved in regulation of fetal growth.


Genome-wide association study of d-amphetamine response in healthy volunteers identifies putative associations, including cadherin 13 (CDH13).
Both the subjective response to d-amphetamine and the risk for amphetamine addiction are known to be heritable traits. Because subjective responses to drugs may predict drug addiction, identifying alleles that influence acute response may also provide insight into the genetic risk factors for drug abuse. We performed a Genome Wide Association Study (GWAS) for the subjective responses to amphetamine in 381 non-drug abusing healthy volunteers. Responses to amphetamine were measured using a double-blind, placebo-controlled, within-subjects design. We used sparse factor analysis to reduce the dimensionality of the data to ten factors. We identified several putative associations; the strongest was between a positive subjective drug-response factor and a SNP (rs3784943) in the 8(th) intron of cadherin 13 (CDH13; P = 4.58×10(-8)), a gene previously associated with a number of psychiatric traits including methamphetamine dependence. Additionally, we observed a putative association between a factor representing the degree of positive affect at baseline and a SNP (rs472402) in the 1(st) intron of steroid-5-alpha-reductase-α-polypeptide-1 (SRD5A1; P = 2.53×10(-7)), a gene whose protein product catalyzes the rate-limiting step in synthesis of the neurosteroid allopregnanolone. This SNP belongs to an LD-block that has been previously associated with the expression of SRD5A1 and differences in SRD5A1 enzymatic activity. The purpose of this study was to begin to explore the genetic basis of subjective responses to stimulant drugs using a GWAS approach in a modestly sized sample. Our approach provides a case study for analysis of high-dimensional intermediate pharmacogenomic phenotypes, which may be more tractable than clinical diagnoses.


Triangles bridge the scales: Quantifying cellular contributions to tissue deformation.
In this article, we propose a general framework to study the dynamics and topology of cellular networks that capture the geometry of cell packings in two-dimensional tissues. Such epithelia undergo large-scale deformation during morphogenesis of a multicellular organism. Large-scale deformations emerge from many individual cellular events such as cell shape changes, cell rearrangements, cell divisions, and cell extrusions. Using a triangle-based representation of cellular network geometry, we obtain an exact decomposition of large-scale material deformation. Interestingly, our approach reveals contributions of correlations between cellular rotations and elongation as well as cellular growth and elongation to tissue deformation. Using this triangle method, we discuss tissue remodeling in the developing pupal wing of the fly Drosophila melanogaster.