cssi/SciSciGPT-SciSciNet huggingface dataset:
Twin Studies of Posttraumatic Stress Disorder: Differentiating Vulnerability Factors from Sequelae

Posttraumatic stress disorder (PTSD) is defined by one's response to an environmental event. However, genetic factors are important in determining people's response to that event, and even their likelihood of being exposed to particular traumatic events in the first place. Classical twin designs can decompose genetic and environmental sources of variance. Such studies are reviewed extensively elsewhere, and we cover them only briefly in this review. Instead, we focus primarily on the identical co-twin control design. This design makes it possible to resolve the "chicken-egg" dilemma inherent in standard case-control designs, namely, distinguishing risk from sequelae. Abnormalities that are present in both the twin with PTSD and the unaffected co-twin suggest pre-existing vulnerability indicators. These include smaller hippocampal volume, large cavum septum pellucidum, more neurological soft signs, lower general intellectual ability, and poorer performance in the specific cognitive abilities of executive function, attention, declarative memory, and processing of contextual cues. In contrast, abnormalities in a twin with PTSD that are not present in the identical co-twin suggest consequences of PTSD or trauma exposure. These include psychophysiological responding, higher resting anterior cingulate metabolism, event-related potential abnormalities associated with attentional processes, recall intrusions, and possibly some types of chronic pain. Most co-twin control studies of PTSD have been small and come from the same twin registry of middle-aged male veterans. Consequently, there is a great need for replication and extension of the findings, particularly in women and younger individuals. The creation of new twin registries would do much toward accomplishing this goal. This article is part of a Special Issue entitled 'Post-Traumatic Stress Disorder'.
R69-18 Multitape One-Way Nonwriting Automata

A multitape one-way nonwriting automaton (MONA) is a finite state machine with a finite number of one-way input tapes which are advanced independently. This paper summarizes closure properties and decision problems of both deterministic and nondeterministic varieties. The family of n-ary word relations defined by deterministic (nondeterministic) n-tape MONA's is called Dn(Nn). Clearly D1 = N1 = regular sets and requires no further comment.
Prescription drug misuse a test of three competing criminological theories

Shifting drug use patterns away from traditional illicit drugs (i.e., heroin, cocaine, methamphetamines) and toward prescription drug misuse among adolescents necessitates a renewed theoretical emp...
Production of q anti-q pairs in proton-nucleus collisions at high energies

We calculate production of quark-antiquark pairs in high energy proton-nucleus collisions both in the quasiclassical approximation of McLerran-Venugopalan model and including quantum small-x evolution. The resulting production cross section is explicitly expressed in terms of Glauber-Mueller multiple rescatterings in the classical case and in terms of dipole-nucleus scattering amplitude in the quantum evolution case. We generalize the result of [K. Tuchin, Phys. Lett. B 593, 66 (2004).] beyond the aligned jet configurations. We expand on the earlier results of Blaizot, Gelis and Venugopalan [J. P. Blaizot, F. Gelis, and R. Venugopalan, Nucl. Phys. A743, 57 (2004).] by deriving quark production cross section including quantum evolution corrections in rapidity intervals both between the quarks and the target and between the quarks and the projectile.
A probabilistic model for fitting MWC polynomials in protein-ligand binding

Abstract Given a binding polynomial in Adair form, A ( x ) = 1 + β 1 x + … + β n x n , β i ⩾ 0, a basic problem is to determine (i) a method of fitting a model polynomial to A ( x ) and (ii) a quantitative measure of the goodness of fit. This paper presents such a method for fitting Monod-Wyman-Changeux (MWC) model polynomials when A ( x ) is of degree three or four. The method of fitting is based on the property that the zeros of an MWC polynomial of any degree lie on a circle in the complex plane. The parameters in the MWC model are determined so that if possible this circle coincides with the circle on which lie the zeros of A ( x ). The measure of goodness of fit is provided by a probabilistic model which gives the probability that a binding polynomial has its zeros on a circle on which lie the zeros of an MWC polynomial and if so, the probability that the juxtaposition of the two sets of zeros can occur by chance alone.
Teaching Strategies for the Forearm Pass in Volleyball

This article shares teaching strategies for the forearm pass in the game of volleyball and identifies how they will help students improve their performance and development of forearm passing skills. The article also provides an assessment rubric to facilitate student understanding of the skill.
Larval distributions in inner‐shelf waters: The roles of wind‐driven cross‐shelf currents and diel vertical migrations

To determine how physical processes and biological behaviors influence larval dispersal on the inner shelf, time series of larval concentrations were quantified during August 1994, on the Outer Banks of North Carolina, U.S.A. Zooplankton pumps, moored in 21 m of water at 3.2, 8.7, and 12.2 m above bottom, collected larvae every 3 h for 3 weeks. Physical variables and larvae were sampled at similar time and space scales. Larval concentrations were typically 10 2 ‐10 4 m 23 for polychaetes, bivalves, and gastropods and 10‐10 2 m 23 for brachyuran crab zoeae. There were two dominant scales of variability, 3‐6 h and 2‐10 d. The high-frequency signal is partially explained by diel vertical migrations—nocturnal ascent and daytime descent. This pattern would allow larvae to feed in subthermocline waters while avoiding visual predators. Low-frequency variations tracked with water temperature. Highest concentrations of worm larvae occurred in cool (upwelled) water and of crab zoeae in warm (downwelled) water. At least two larval groups comprised the clam and snail time series, one with fairly high abundances in cool water and the other with peak concentrations in warm water. Wind-driven cross-shelf transport is the most plausible explanation for these low-frequency fluctuations. For example, dense patches of worm larvae overlying parental habitat (offshore muds) would be carried shoreward in cool, upwelling flows. In contrast, brachyuran zoeae in nearsurface waters would descend at the coast during downwelling and, together with larvae aloft nearshore sediments, be transported seaward below the thermocline. Thus advected by strong along-shore and weaker cross-shelf currents, larvae zigzag up and down the coast. Vertically traversing the water column while they feed and grow, larvae ultimately seek a suitable habitat in which to settle.
ROS upregulation during the early phase of retroviral infection plays an important role in viral establishment in the host cell

Recent studies suggest that low levels of reactive oxygen species (ROS) often modulate normal intracellular signalling pathways, determine cell fates and control cell proliferation. We found that infection of astrocytes with the neuropathogenic retrovirus ts1, a mutant of Moloney murine leukemia retrovirus, upregulated ROS at low levels during the early phase of infection. This upregulation of intracellular ROS with downregulation of NADPH levels during the early phase of ts1 infection was a separate event from the upregulation of ROS during the late phase while ts1-mediated cell death occurred. The treatment of apocynin, a potential inhibitor of NADPH oxidase (NOX), inhibited establishment of the ts1 virus in the host cell. These results suggested that ROS generated as a consequence of the activation of NOX may play an important role in the early events of the virus life cycle leading to the establishment of the virus in the host cell. The in vitro results were further supported by an in vivo experiment which showed that the treatment of apocynin decreased viral titre in the ts1-infected mouse brain and increased the lifespan of infected mice. This study provides the first in vitro and in vivo evidence on a mechanism for how ROS are involved in ts1 retrovirus infection and ts1-mediated neurodegenerative disease. Our findings focusing on the early phase of the ts1 retrovirus life cycle could provide a better understanding of retroviral life cycle, which may offer specific therapeutic targets for suppressing viral replication and alleviating neurodegenerative symptoms in a mouse model.
Polyamines regulate intestinal epithelial restitution through TRPC1-mediated Ca2+ signaling by differentially modulating STIM1 and STIM2

Early epithelial restitution occurs as a consequence of intestinal epithelial cell (IEC) migration after wounding, and its defective regulation is implicated in various critical pathological conditions. Polyamines stimulate intestinal epithelial restitution, but their exact mechanism remains unclear. Canonical transient receptor potential-1 (TRPC1)-mediated Ca2+ signaling is crucial for stimulation of IEC migration after wounding, and induced translocation of stromal interaction molecule 1 (STIM1) to the plasma membrane activates TRPC1-mediated Ca2+ influx and thus enhanced restitution. Here, we show that polyamines regulate intestinal epithelial restitution through TRPC1-mediated Ca2+ signaling by altering the ratio of STIM1 to STIM2. Increasing cellular polyamines by ectopic overexpression of the ornithine decarboxylase (ODC) gene stimulated STIM1 but inhibited STIM2 expression, whereas depletion of cellular polyamines by inhibiting ODC activity decreased STIM1 but increased STIM2 levels. Induced STIM1/TRPC1 association by increasing polyamines enhanced Ca2+ influx and stimulated epithelial restitution, while decreased formation of the STIM1/TRPC1 complex by polyamine depletion decreased Ca2+ influx and repressed cell migration. Induced STIM1/STIM2 heteromers by polyamine depletion or STIM2 overexpression suppressed STIM1 membrane translocation and inhibited Ca2+ influx and epithelial restitution. These results indicate that polyamines differentially modulate cellular STIM1 and STIM2 levels in IECs, in turn controlling TRPC1-mediated Ca2+ signaling and influencing cell migration after wounding.
SACCHAROMYCES CEREVISIAE MOD5P-II CONTAINS SEQUENCES ANTAGONISTIC FOR NUCLEAR AND CYTOSOLIC LOCATIONS

MOD5 encodes a tRNA modification activity located in three subcellular compartments. Alternative translation initiation generates Mod5p-I, located in the mitochondria and the cytosol, and Mod5p-II, located in the cytosol and nucleus. Here we study the nucleus/cytosol distribution of overexpressed Mod5p-II. Nuclear Mod5p-II appears concentrated in the nucleolus, perhaps indicating that the nuclear pool may have a different biological role than the cytoplasmic and mitochondrial pools. Mod5p contains three motifs resembling bipartite-like n uclear l ocalization s equences (NLSs), but only one is sufficient to locate a passenger protein to the nucleus. Mutations of basic residues of this motif cumulatively contribute to a cytosolic location for the fusion proteins. These alterations also cause decreased nuclear pools of endogenous Mod5p-II. Depletion of nuclear Mod5p-II does not affect tRNA Tyr function. Despite the NLS, most Mod5p is cytosolic. We assessed whether Mod5p sequences cause a karyophilic reporter to be located in the cytosol. By this assay, Mod5p may contain more than one region that functions as cytoplasmic retention and/or nuclear export sequences. Thus, distribution of Mod5p results from the presence/absence of mitochondrial targeting information and sequences antagonistic for nuclear and cytosolic locations. Mod5p is highly conserved; sequences responsible for subcellular distribution appear to reside in “accessory” motifs missing from prokaryotic counterparts.
Thin AC converters — A new approach for making existing grid assets smart and controllable

Existing techniques for realizing dynamic grid control have involved the use of FACTS devices such as STATCOMs, where the desired functionality is obtained in a single dasiablack-boxpsila device. These devices are deployed in addition to resources that already exist on the grid. This paper proposes a new approach for using dasiathin AC converterspsila to convert existing dasiadumbpsila grid assets into dasiasmart and controllablepsila assets, resulting in significant cost reduction and enhanced asset availability. The technique is seen to be scalable to high power levels, and can convert shunt VAR capacitors into STATCOMs, and can convert load tap changing transformers into dynamic network control devices. New dasiathin AC converterpsila topologies for realizing high-voltage and high-power are detailed along with analysis, control and operating results.
Best (but oft-forgotten) practices: checking assumptions concerning regression residuals

The residuals of a least squares regression model are defined as the observations minus the modeled values. For least squares regression to produce valid CIs and P values, the residuals must be independent, be normally distributed, and have a constant variance. If these assumptions are not satisfied, estimates can be biased and power can be reduced. However, there are ways to assess these assumptions and steps one can take if the assumptions are violated. Here, we discuss both assessment and appropriate responses to violation of assumptions.
Sodium Recovery from Normal and Edematous Lungs Studied by Indicator Dilution Curves

We attempted to measure sodium and water spaces in the lungs before and after pulmonary edema produced in dogs by increasing pulmonary capillary pressure or by alloxan. We employed a technique depending on the difference in transit times through the lungs of tritiated water or 24Na+, with reference to an intravascular indicator. In the control measurements, there was virtually complete recovery of the sodium indicator, but in pulmonary edema there was a significant loss. It is possible that this represents distribution of some of the 24Na+ into an extravascular volume with an exit other than the pulmonary veins, but we would expect this to be accompanied by an equivalent amount of tritiated water. Since there was complete recovery of tritiated water in pulmonary edema, it seems more likely that the sodium loss represents binding by some extravascular locus and may be related to the extent of alveolar wall injury.
Computer Use, Internet Access, and Online Health Searching Among Harlem Adults

Abstract Purpose. Computer use, Internet access, and online searching for health information were assessed toward enhancing Internet use for health promotion. Design. Cross-sectional random digit dial landline phone survey. Setting. Eight zip codes that comprised Central Harlem/Hamilton Heights and East Harlem in New York City. Subjects. Adults 18 years and older (N = 646). Measures. Demographic characteristics, computer use, Internet access, and online searching for health information. Analysis. Frequencies for categorical variables and means and standard deviations for continuous variables were calculated and compared with analogous findings reported in national surveys from similar time periods. Results. Among Harlem adults, ever computer use and current Internet use were 77% and 52%, respectively. High-speed home Internet connections were somewhat lower for Harlem adults than for U.S. adults overall (43% vs. 68%). Current Internet users in Harlem were more likely to be younger, white vs. black or Hi...
Strategies and issues in applications of neural networks

The authors survey some of the fundamental aspects of neural networks that have been found crucial to their application to practical problems in diagnostics, modeling, and control. The analysis is a loosely connected collection of remarks on difficulties that have been encountered and the approach to dealing with them. Promising approaches now being explored and suggestions for future work are outlined. The issues raised concern the following: neural nets and engineering; training by higher order methods; sparse data and generalization; local representation networks; prestructured networks; scaling nodes; context switching; recurrent networks; neural controller development; and fusion of neural nets and fuzzy logic. >
Functional Consequences of Exchanging Domains Between LacI and PurR are Mediated by the Intervening Linker Sequence

Homologue function can be differentiated by changing residues that affect binding sites or long-range interactions. LacI and PurR are two proteins that represent the LacI/GalR family (>500 members) of bacterial transcription regulators. All members have distinct DNA-binding and regulatory domains linked by approximately 18 amino acids. Each homologue has specificity for different DNA and regulatory effector ligands; LacI and PurR also exhibit differences in allosteric communication between DNA and effector binding sites. A comparative study of LacI and PurR suggested that alterations in the interface between the regulatory domain and linker are important for differentiating their functions. Four residues (equivalent to LacI positions 48, 55, 58, and 61) appear particularly important for creating a unique interface and were predicted to be necessary for allosteric regulation. However, nearby residues in the linker interact with DNA ligand. Thus, differences observed in interactions between linker and regulatory domain may be the cause of altered function or an effect of the two proteins binding different DNA ligands. To separate these possibilities, we created a chimeric protein with the LacI DNA-binding domain/linker and the PurR regulatory domain (LLhP). If the interface requires homologue-specific interactions in order to propagate the signal from effector binding, then LLhP repression should not be allosterically regulated by effector binding. Experiments show that LLhP is capable of repression from lacO1 and, contrary to expectation, allosteric response is intact. Further, restoring the potential for PurR-like interactions via substitutions in the LLhP linker tends to diminish repression. These effects are especially pronounced for residues 58 and 61. Clearly, binding affinity of LLhP for the lacO1 DNA site is sensitive to long-range changes in the linker. This result also raises the possibility that mutations at positions 58 and 61 co-evolved with changes in the DNA-binding site. In addition, repression measured in the absence and presence of effector ligand shows that allosteric response increases for several LLhP variants with substitutions at positions 48 and 55. Thus, while side chain variation at these sites does not generally dictate the presence or absence of allostery, the nature of the amino acid can modulate the response to effector.
The rationale and technique of staged-volume arteriovenous malformation radiosurgery.

Abstract Purpose: Stereotactic radiosurgery is an effective management strategy for properly selected arteriovenous malformation (AVM) patients. However, the risk of postradiosurgical radiation-related injury generally limits this procedure to patients with AVMs of an average diameter of 3 cm or less. Radiosurgery of large AVMs in a planned staged fashion was undertaken to limit the radiation exposure to the surrounding normal brain. Methods and Materials: Between April 1997 and December 1999, 10 patients with a median AVM volume of 17.4 cm 3 (range, 7.4–53.3 cm 3 ) underwent staged-volume radiosurgery (23 procedures). At the first radiosurgical procedure, the total volume of the AVM is estimated and a dose plan calculated that covers 10 cm 3 –15 cm 3 , or one-half the nidus volume if the AVM is critically located (brainstem, thalamus, or basal ganglia). At 6-month intervals thereafter, radiosurgery was repeated to different portions of the AVM with the previous dose plan(s) being re-created utilizing intracranial landmarks to minimize radiation overlap. Radiosurgical procedures were continued until the entire malformation has been irradiated. Results: The radiation dosimetry of staged-volume AVM radiosurgery was compared to hypothetical single-session procedures for the 10 patients. Staged-volume radiosurgery decreased the 12-Gy volume by an average of 11.1% (range, 4.9–21%) ( p p Discussion: Staged-volume radiosurgery of large AVMs results in less radiation exposure to the adjacent brain. Further follow-up is needed to determine whether this technique provides a high rate of AVM obliteration while maintaining an acceptable rate of radiation-related complications.
What's in a Relationship? An Examination of Social Capital, Race and Class in Mentoring Relationships

After 25 years of intense scrutiny, social capital remains an important yet highly debated concept in social science research. This research uses data from youth and mentors in several chapters of Big Brothers/Big Sisters to assess the importance of different mentoring relationship characteristics in creating positive outcomes among youths. The literature on social capital suggests that key characteristics are: (1. the amount of time spent between individuals, (2. racial similarity, (3. level of trust, (4. social class difference, and (5. intergenerational closure. I examine the effects of these social capital measures on academic and deviant behavioral outcomes and run models using propensity score weights to address selection bias. The results indicate that both the amount of time spent in a relationship and the level of trust consistently have positive effects for youths. Counter to what some theory suggests, race-matching and closure between parent and mentor have limited effects, and social class difference between individuals has no significant effect on any of the examined outcomes. These findings have important implications for future work on social capital and adolescent relationships in general.
Case-Control Study of Malignant Melanoma in Washington State II. Diet, Alcohol, and Obesity

Intakes of vitamin A, dietary antioxidants, and other dietary components were examined for their relation to the risk of malignant melanoma among 234 cases and 248 controls in three counties of western Washington State. Cases were drawn from persons diagnosed with melanoma between 1984 and 1987 and identified through a Seattle-Puget Sound cancer registry. Population controls were identified through random digit dialing and were randomly selected, stratified by age, sex, and county. Subjects completed a telephone interview and a mailed food frequency questionnaire asking for information on diet, demographic factors, and factors known to be associated with melanoma. Subjects were asked to estimate their food intake 7 years prior to diagnosis for cases and during a comparable time period for controls. Among data on 16 nutrients calculated from reported food intake, one significant finding emerged: Vitamin E obtained from food was inversely related to risk of melanoma (for highest quartile vs. lowest quartile, age-, education-, and energy intake-adjusted odds ratio (OR) = 0.34, 95% confidence interval (CI) 0.16-0.72; p for trend = 0.01). When intake of nutrients from food plus vitamin and mineral supplements was considered, zinc from food and supplements was associated with a decreased risk of melanoma (for highest quartile vs. lowest quartile, adjusted OR = 0.46, 95% CI 0.24-0.91; p for trend = 0.01). There was no evidence that vitamin A, preformed retinol, or carotenoids were associated with a decreased risk of melanoma or that alcohol or polyunsaturated fats were associated with an increased risk. Body mass index (weight (kg)/height (m)2) was significantly related to melanoma risk; cases were more obese than controls (for highest quartile vs. lowest quartile, age-, sex-, and education-adjusted OR = 1.90, 95% CI 1.10-3.27; p for trend = 0.02). These results provide limited support for the hypothesis that antioxidants such as vitamin E or cofactors in protection from oxidative damage such as zinc may be protective for melanoma, and they suggest that obesity should be measured in future studies of melanoma.
Abstract 58: Delayed Atherosclerosis in a Mouse Model of Bernard-Soulier Syndrome is Independent of Glycoprotein Ibα Extracytoplasmic Domain Deficiency

The pathogenesis of atherosclerosis involves the interplay of blood, stromal and endothelial cells; platelet interactions with vascular endothelium and leukocytes promote atherosclerosis. Glycoprotein (GP) Iba is the ligand-binding subunit of the platelet GPIb-IX-V adhesion receptor complex; its deficiency causes the Bernard-Soulier syndrome (BSS), characterized by absent platelet GPIb-IX-V, macrothrombocytopenia and bleeding. We found that Ldlr-/- mice reconstituted with GPIba-/- as compared to wild type control developed delayed atherosclerosis associated with reduced platelet binding to blood myeloid cells and reduced accumulation of CD11b+ and CD11c+ myeloid cells in the aortas. Live imaging in whole blood-perfused microfluidic chambers revealed reduced platelet-monocyte aggregates in GPIba-/- mice, which also showed decreased TNF in blood monocytes along with decreased TNF and IL12p35, but enhanced arginase1 in aortas. In contrast, Ldlr-/- mice reconstituted with chimeric IL-4R/GPIba-Tg bone marrow p...
Recent Issues in Antihypertensive Drug Therapy

Results of recent large scale treatment trials have demonstrated that aggressive management of high blood pressure prevents progression of mild hypertension to the accelerated or malignant phase and reduces incidence of stroke, congestive heart failure, and left ventricular hypertrophy. These trials mostly have utilized a diuretic-based, stepped-care approach to drug therapy, however, and have not shown a consistent beneficial effect of treatment on coronary heart mortality. In addition, the results of studies such as MRFIT have raised questions about serious risks of diuretic treatment in selected patients. These concerns have led to increased use of nonpharmacologic approaches to lowering blood pressure in patients with mild hypertension, but most patients ultimately require drug therapy. Alternative agents to diuretics now being employed as monotherapy in mild hypertension include beta-blockers, calcium channel blockers, ACE inhibitors, alpha-blockers, alpha- and beta-blockers, and, to a lesser extent, centrally-acting sympatholytics and peripheral adrenergic antagonists. Rational use of these agents primarily is based on a careful evaluation of concomitant medical conditions (see Table 3), as well as their mode of action, relative side effects, ease of administration, and cost. Age and race recently have been found to be important determinants of antihypertensive response to agents such as diuretics, beta-blockers, calcium channel blockers, and ACE inhibitors (see Table 3) and appreciation of these relative differences may affect drug selection. When these factors are taken into account, an effective and well tolerated regimen can be tailored to the individual patient. It is hoped that aggressive treatment of hypertension in the future will cause a further decline in cardiovascular mortality in the United States.
PERSPECTIVE METAZOAN COMPLEXITY AND EVOLUTION: IS THERE A TREND?

The notion that complexity increases in evolution is widely accepted, but the best-known evidence is highly impressionistic. Here I propose a scheme for understanding complexity that provides a conceptual basis for objective measurement. The scheme also shows complexity to be a broad term covering four independent types. For each type, I describe some of the measures that have been devised and review the evidence for trends in the maximum and mean. In metazoans as a whole, there is good evidence only for an early-Phanerozoic trend, and only in one type of complexity. For each of the other types, some trends have been documented, but only in a small number of metazoan subgroups.
Species differences in intrinsic myocardial contractility.

SummaryLeft ventricular myocardial contractility has been estimated in terms of contractile element force-velocity relations in five mammalian species. Contractility appeared to differ in different species and to be related to natural heart rate.
Synopsis of the New World Species of the Dipterous Family Asteiidae

Over ten years ago I published a revision and catalogue of the New World flies of the small family Asteiidae (Sabrosky, 1943). Since that time the discovery of new species and the accumulation of miscellaneous notes and corrections have made it desirable to bring the revision up to date The present paper, which includes two new genera and 24 new species, raises from 18 to 43 the number of recognized New World species.
Effects of Dipterous Parasites on Production and Viability of Melanoplus sanguinipes Eggs (Orthoptera: Acrididae)

Field-collected Melanoplus sanguinipes (F.) were reared in laboratory containers as isolated male/female couples, and the parasitization status of each individual was determined. Although number of eggs per pod and viability of eggs were similar for all females, parasitized females produced fewer egg pods than nonparasitized females.
Effect of hyaluronidase on tissue‐engineered human septal cartilage

Objectives Structural properties of tissue-engineered cartilage can be optimized by altering its collagen to sulfated glycosaminoglycan (sGAG) ratio with hyaluronidase. The objective was to determine if treatment of neocartilage constructs with hyaluronidase leads to increased collagen:sGAG ratios, as seen in native tissue, and improved tensile properties. Study Design Prospective, basic science. Methods Engineered human septal cartilage from 12 patients was treated with hyaluronidase prior to culture. Control and treated constructs were analyzed at 3, 6, or 9 weeks for their biochemical, biomechanical, and histological properties. Results Levels of sGAG were significantly reduced in treated constructs when compared with control constructs at 3, 6, and 9 weeks. Treated constructs had higher collagen:sGAG ratios when compared with control constructs at 3, 6, and 9 weeks. Treated constructs had greater tensile strength, strain at failure, and increased stiffness as measured by the equilibrium and ramp tensile moduli when compared with the untreated control constructs. Continued time in culture improved tensile strength in both treated and control constructs. Conclusion Hyaluronidase treatment of engineered septal cartilage decreased total sGAG content without inhibiting expansive growth of the constructs. Decreased sGAG in treated constructs resulted in increased collagen to sGAG ratios and was associated with an increase in tensile strength and stiffness. With additional culture time, sGAG increased modestly in depleted constructs, and some initial gains in tensile properties were dampened. Alterations in the dosage of hyalurondiase during neocartilage fabrication can create constructs that have improved biomechanical properties for eventual surgical implantation. Level of Evidence NA. Laryngoscope, 2016
The PTEN/PI3 Kinase Pathway in Human Glioma

Phosphoinositide 3-kinase (PI3K) was discovered over 20 years ago as an enzyme that was active in growth factor-stimulated and oncogene-transformed cells. Ten years later, the PTEN gene was isolated by its deletion in a large proportion of human cancers, including glioblastoma. These two areas of research converged when it was shown that PTEN dephosphorylated the lipid product of PI3K activity, phosphatidylinositol (3,4,5) trisphosphate, or PIP3. Furthermore, it has since become clear that PTEN has tumor-suppressive activities that are independent of its lipid phosphatase activity. This chapter reviews the importance of PI3K activity in the development of glioblastoma, by describing the different genetic and epigenetic alterations that occur to deregulate the activity of this pathway. It will also describe the regulation of PTEN expression and activity, by transcriptional and posttranslational processes. Recent results implicating PI3K activity and PTEN in the cells that are thought to initiate early brain tumor development (brain tumor stem cells) are also reviewed. Finally, the possibilities of using this pathway both as a direct therapeutic target and as a way of predicting response to recently developed drugs are discussed.
Acquirement of Rituximab Resistance Is Associated with the Development of Chemotherapy Resistance in B-Cell Lymphoma Cells: Evidence of Shared Pathways of Resistance between Chemotherapeutic Agents and Biological Therapies.

Pre-clinical studies have demonstrated that rituximab triggers apoptotic signals in B-cell lymphoma cells upon biding to CD20 antigen. Downstream signaling events observed in lymphoma cells following in vitro exposure of rituximab or chemotherapy include: 1) activation of the intrinsic apoptotic pathway and 2) increased mitogen activated protein kinase (MAPK) activity. In addition, pre-clinical and clinical studies strongly suggest that rituximab may sensitize lymphoma cells to apoptotic effects of various drugs used to treat NHL. Despite its anti-tumor activity, many patients relapse after initial response to rituximab-based therapy and demonstrate variable degrees of rituximab resistance. To further study the impact of rituximab resistance in cellular responses to chemotherapy we developed several rituximab resistant cell lines (RRCL) derived from Raji, SU-DHL-4 and RL cells by exposing cells to escalating doses of rituximab with (4RH cells) or without (2R cells) human serum. The rituximab resistance of each RRCL was confirmed by immunological assays. Subsequently, lymphoma cells (parental and RRCL) were exposed to various chemotherapeutic agents (cisplatin, doxorubicin, paclitaxel, or vincristine) for up to 48 hours. Detection of cell death was determined by trypan blue and/or propidium iodine staining. Caspase-3 activity was measured by PhiPhi Lux G1D2 enzymatic cleavage. Bcl-2 expression was determined by Western blotting. Chemotherapy resistance to all agents tested was observed in RRCL when compared to parental Raji, SU-DHL-4 and RL cell lines. In addition, caspase-3 activity was lower in RRCL following chemotherapy exposure than in parental cell lines. A significantly lower percent of RRCL cells within sub-G0/G1 peaks in cell cycle histograms confirmed that RRCL were less sensitive to chemotherapy-induced apoptosis. Additionally, an increase in Bcl-2 expression was observed in RRCL when compared parental cell lines. Our data strongly suggest that chemotherapy resistance emerges concomitantly with the acquirement of rituximab resistance in lymphoma cells. Chronic exposure to rituximab appears to cause overexpression of Bcl-2, which likely renders RRCL less susceptible to the apoptotic effects of chemotherapy agents. Ongoing studies are aimed at identifying and overcoming rituximab/chemotherapy shared cellular pathways of resistance.
Progress in Sympathetically Mediated Pathological Pain

Aim of review: Many chronic pain conditions remain difficult to treat, presenting a high burden to society. Conditions such as complex regional pain syndrome may be maintained or exacerbated by sympathetic activity. Understanding the interactions between sympathetic nervous system and sensory system will help to improve the effective management of pathological pain including intractable neuropathic pain and persistent inflammatory pain. Method: We first described the discovery of abnormal connections between sympathetic and sensory neurons. Subsequently, the functional roles of sympathetic sprouting in altered neuronal excitability and increased pain sensitivity were discussed. The mechanisms of the sympathetic sprouting were focusing on its relationship with neurotrophins, local inflammation, and abnormal spontaneous activity. Finally, we discussed clinical implications and conflicting findings in the laboratory and clinical research with respect to the interaction between sympathetic system and sensory system.Recent findings: The findings that sprouting of sympathetic fibers into the sensory ganglia (dorsal root ganglion) after peripheral nerve injury, offers a possible explanation of the sympathetic involvement in pain. It is also suggested that releases of adenosine triphosphate (ATP), in addition to norepinephrine, from sympathetic nerve endings play important roles in sympathetic-mediated pain. New evidence indicates the importance of sympathetic innervation in local inflammatory responses.Summary: Hopefully, this review will reinvigorate the study of sympathetic-sensory interactions in chronic pain conditions, and help to better understand how sympathetic system contributes to this serious clinical problem. Citation: Si-Si Chen, Jun-Ming Zhang. Progress in sympathetically mediated pathological pain. J Anesth Perioper Med 2015; 2: 216-25. doi: 10.24015/JAPM.2015.0029This is an open-access article, published by Evidence Based Communications (EBC). This work is licensed under the Creative Commons Attribution 4.0 International License, which permits unrestricted use, distribution, and reproduction in any medium or format for any lawful purpose. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
The Use of Mesh Plates for Difficult Fractures of the Patella.

Patella fractures present some of the more complicated fracture patterns in orthopaedic trauma care. This is partially due to the small size of the fragments but also the articular nature of each fragment. Fixation methods such as cerclage wiring, excision of smaller fragments, and screw fixation of larger fragments all have their own challenges. Our study examined our Level I trauma center's experience with variable angle locked 2.7 mm titanium plates for treatment of comminuted patella fractures or treatment of patellar nonunion. After Institutional Review Board approval, we used billing records to identify 105 patients who had undergone operative management of a displaced patella fracture between January 2011 and December 2015. We reviewed the radiographs of these patients to identify which patients underwent treatment with a mesh plate. We found 16 patients (6 males and 10 females) who had undergone fixation with a mesh plate; mean age was 47 years. Nine patients underwent primary open reduction internal fixation (ORIF) and seven underwent mesh plate fixation for failed ORIF of a patella fracture. The mean visual analog pain score was 2.75 (range, 0–9). The mean range of motion was 1 degree of extension (range, 0–10 degrees) to 110 degrees of flexion (range, 45–135 degrees). All fractures healed. Five patients required hardware removal for pain. This review illustrates the effectiveness of the locking mesh plate in two challenging clinical scenarios: that of patellar nonunion and comminuted fractures that preclude standard fixation methods. Although multiple options exist for patellar fracture fixation, the titanium mesh locking plate can be an effective option for retaining the patella in the setting of comminution. Further comparative studies should be undertaken to determine which method of treatment may be superior in the treatment of these fractures.
How are base excision DNA repair pathways deployed in vivo

Since the discovery of the base excision repair (BER) system for DNA more than 40 years ago, new branches of the pathway have been revealed at the biochemical level by in vitro studies. Largely for technical reasons, however, the confirmation of these subpathways in vivo has been elusive. We review methods that have been used to explore BER in mammalian cells, indicate where there are important knowledge gaps to fill, and suggest a way to address them.
A Mechanistic Understanding of Pyroptosis: The Fiery Death Triggered by Invasive Infection

Immune cells and skin and mucosal epithelial cells recognize invasive microbes and other signs of danger to sound alarms that recruit responder cells and initiate an immediate "innate" immune response. An especially powerful alarm is triggered by cytosolic sensors of invasive infection that assemble into multimolecular complexes, called inflammasomes, that activate the inflammatory caspases, leading to maturation and secretion of proinflammatory cytokines and pyroptosis, an inflammatory death of the infected cell. Work in the past year has defined the molecular basis of pyroptosis. Activated inflammatory caspases cleave Gasdermin D (GSDMD), a cytosolic protein in immune antigen-presenting cells and epithelia. Cleavage separates the autoinhibitory C-terminal fragment from the active N-terminal fragment, which moves to the cell membrane, binds to lipids on the inside of the cell membrane, and oligomerizes to form membrane pores that disrupt cell membrane integrity, causing death and leakage of small molecules, including the proinflammatory cytokines and GSDMD itself. GSDMD also binds to cardiolipin on bacterial membranes and kills the very bacteria that activate the inflammasome. GSDMD belongs to a family of poorly studied gasdermins, expressed in the skin and mucosa, which can also form membrane pores. Spontaneous mutations that disrupt the binding of the N- and C-terminal domains of other gasdermins are associated with alopecia and asthma. Here, we review recent studies that identified the roles of the inflammasome, inflammatory caspases, and GSDMD in pyroptosis and highlight some of the outstanding questions about their roles in innate immunity, control of infection, and sepsis.
Assessment of vestibulo-ocular function without measuring eye movements

Abstract Background The vestibulo-ocular reflex (VOR) maintains stable gaze during head motion. Deficiencies lead to apparent world motion due to incomplete stabilization of eyes in space. VOR measurement requires specialized apparatus, trained operators, and significant setup time. New method We present a system (VON: vestibulo-ocular nulling ) for rapid vestibulo-ocular assessment without measuring eye movements per se . VON uses a head-mounted motion sensor, laptop computer with user input control, and laser target whose position is controlled by the computer. As the head moves, the target is made to move in the same manner with a gain set by the subject. When the subject sets the gain so the target appears stationary in space, it is stationary on the retinas. One can determine from this gain the extent to which the eyes move in space when the head moves, which is the amount by which the VOR is deficient. From this the gain of the compensatory eye movements is derived. Results VON was compared with conventional video-based VOR measures. Both methods track expected changes in gain over 20 min of adaptation to minifying spectacles. VON measures are more consistent across subjects, and pre-adaptation values are closer to compensatory. Comparison with existing method VON is a rapid means to assess vestibulo-ocular performance. As a functional perceptual measure, it accounts for gaze-stabilizing contributions that are not apparent in the standard VOR, such as pursuit and perceptual tolerance. Conclusions VON assesses functional VOR performance. Future implementations will make VOR assessment widely available to investigators and clinicians.
Evaluating the Use of LINE Software to Support Interaction During an American Travel Course in Japan

This paper describes our use of the LINE social media software system to promote interaction, convey mood and emotion, and teach students about Kawaii culture during an international travel course that exposes undergraduate students at an American liberal arts college to Japanese culture, technology and design. The LINE user experience incorporates the important Japanese pop-culture principle of Kawaii (cuteness in the context of Japanese culture) and Japanese users enjoy interacting with LINE’s Kawaii interface. We report on our method of integrating LINE software into an international travel course and our evaluation of how students compare LINE’s Kawaii interface with the communication tools and social media tools that they are more familiar with. We also report on the extent to which the students believe that using LINE helped them understand Kawaii design. We also report on opportunities and barriers associated with cross-cultural adoption of social media platforms.
Translating evidence into practice in acute respiratory distress syndrome: teamwork, clinical decision support, and behavioral economic interventions.

Purpose of reviewAlthough the treatment of the acute respiratory distress syndrome (ARDS) with low tidal volume (LTV) mechanical ventilation improves mortality, it is not consistently administered in clinical practice. This review examines strategies to improve LTV and other evidence-based therapies
The effect of electronic health record software design on resident documentation and compliance with evidence-based medicine.

This study aimed to determine the role of electronic health record software in resident education by evaluating documentation of 30 elements extracted from the American Academy of Ophthalmology Dry Eye Syndrome Preferred Practice Pattern. The Kresge Eye Institute transitioned to using electronic health record software in June 2013. We evaluated the charts of 331 patients examined in the resident ophthalmology clinic between September 1, 2011, and March 31, 2014, for an initial evaluation for dry eye syndrome. We compared documentation rates for the 30 evidence-based elements between electronic health record chart note templates among the ophthalmology residents. Overall, significant changes in documentation occurred when transitioning to a new version of the electronic health record software with average compliance ranging from 67.4% to 73.6% (p 90%) in 13 elements while Electronic Health Record B had high compliance (>90%) in 11 elements. The presence of dialog boxes was responsible for significant changes in documentation of adnexa, puncta, proptosis, skin examination, contact lens wear, and smoking exposure. Significant differences in documentation were correlated with electronic health record template design rather than individual resident or residents' year in training. Our results show that electronic health record template design influences documentation across all resident years. Decreased documentation likely results from "mouse click fatigue" as residents had to access multiple dialog boxes to complete documentation. These findings highlight the importance of EHR template design to improve resident documentation and integration of evidence-based medicine into their clinical notes.
Predicting Distal Aortic Remodeling After Endovascular Repair for Chronic DeBakey III Aortic Dissection

Background Chronic DeBakey III aortic dissection is typically managed with open aortic reconstruction. Thoracic endovascular aortic grafting (TEVAR) has been attempted in patients with chronic DeBakey III with improved outcomes over medical management, however with frequent failures. This study investigates factors associated with positive aortic remodeling from a large aortic center. Methods Three-dimensional reconstructions (M2S, West Lebanon, NH) of computed tomography angiography scans of 48 patients who underwent TEVAR from 2005 to 2015 were analyzed. The dissection was characterized, and measurements were obtained from preoperative and postoperative scans at four time points. Standard univariate Wilcoxon rank sum and Fisher's exact tests were used to analyze continuous and ordinal/nominal data, respectively. Multivariable logistic regression was performed. Results In a multivariate logistic model, having fewer than two visceral vessels off the true lumen was a negative predictor of total thrombosis (odd ratio [OR] 0.01, 95% confidence interval [CI]: Conclusions TEVAR is feasible in chronic dissection but is limited by complex dissection-related anatomy. Increasing number of visceral vessels off the false lumen, maximum preoperative aortic size, and location of the primary tear on the greater curve were associated with poorer remodeling.