A computer simulation of progesterone and Cox2 inhibitor treatment for preterm labor.
Sufficient information from in vitro and in vivo studies has become available to permit computer modeling of the processes that occur in the myometrium during labor. This development allows the in silico investigation of pathological mechanisms and the trialing of potential treatments. Based on the human literature, we developed a computer model of the immune-endocrine environment of the myometrial cell. The interactions between molecules are represented by differential equations. The model is designed to simulate the estrogen and progesterone receptor changes during pregnancy and particularly the changes in the progesterone receptor (PR) isoforms A and B that are thought to mediate functional progesterone withdrawal in the human at labor. Parturition is represented by an increase in the PRA to PRB ratio to levels seen in women in labor. Infection is shown by inducing inflammation in the system by increasing phospho-IkB kinase concentration (IKK) levels; which lead to increased NF-kappaB activation, causing an increase in the PRA/PRB ratio. We examined the effects of progesterone or cyclo-oxygenase 2 (Cox2) inhibitor treatments on the PRA/PRB ratio in silico. The model predicted that high doses of progesterone and Cox2 inhibition would be effective in preventing an NF-kappaB-induced PRA/PRB ratio increase to the levels found during labor. Our data illustrate the use of dynamic biological computer simulations to test the effectiveness of therapeutic interventions. This may allow the early rejection of ineffective therapies prior to expensive field trials.


Neuropilin-1 contributes to esophageal squamous cancer progression via promoting P65-dependent cell proliferation.
Neuropilin-1 (NRP1) is a non-kinase receptor recently implicated in tumor progression. Here we revealed that over-expression of NRP1 correlates with poor prognosis in esophageal squamous cell carcinoma (ESCC). NRP1-knockdown suppressed ESCC cell proliferation and xenograft tumor growth. Reduced NRP1 expression downregulated P65 mRNA and protein expression, and ectopic expression of P65-restored cell proliferation in NRP1-silenced cells. NRP1 regulates P65 transcription by activating cAMP responsive element binding protein (CREB). NRP1 interacted with and activated epidermal growth factor receptor (EGFR), and b1/b2 domain of NRP1 is responsible for the activation of EGFR. We also found that EGFR regulated CREB transcriptional activity via AKT. These data suggest that NRP1 is an upstream regulator in the P65-dependent proliferation signaling pathway and a candidate therapeutic target for ESCC.


Endothelin-1-mediated cerebrovascular remodeling is not associated with increased ischemic brain injury in diabetes.
Diabetes increases the risk of as well as poor outcome after stroke. Matrix metalloprotease (MMP) activation disrupts blood-brain barrier integrity after cerebral ischemia. We have previously shown that type 2 diabetes promotes remodeling of middle cerebral arteries (MCA) characterized by increased media/lumen (M/L) ratio and MMP activity in an endothelin (ET)-1-dependent manner in the Goto-Kakizaki (GK) rat model. In the present study, we examined the effects of ET-1-mediated vascular remodeling on neurovascular damage following cerebral ischemic injury in GK rats 5 and 12 weeks after the onset of diabetes. The MCA structure, cerebral perfusion as well as infarct size, and hemorrhage were measured in control and diabetic rats subjected to transient MCA occlusion. M/L ratio was increased after 12 but not 5 weeks of diabetes. The baseline cerebral perfusion was lower and the infarct volume smaller in diabetic rats in both age groups. The incidence of hemorrhagic transformation was higher after 5 weeks of diabetes as compared to that after 12 weeks or in the control groups. These findings provide evidence that ET-1-mediated cerebrovascular remodeling does not worsen the neurovascular damage of ischemic brain injury in diabetes. It is possible that this early remodeling response is compensatory in nature to regulate vascular tone and integrity, especially when ischemia is layered on diabetic vascular disease.


Links between electrophysiological and molecular pathology of amyotrophic lateral sclerosis.
Multiple deficits have been described in amyotrophic lateral sclerosis (ALS), from the first changes in normal functioning of the motoneurons and glia to the eventual loss of spinal and cortical motoneurons. In this review, current results, including changes in size, and electrical properties of motoneurons, glutamate excitotoxicity, calcium buffering, deficits in mitochondrial and cellular transport, impediments to proteostasis which lead to stress of the endoplasmic reticulum (ER), and glial contributions to motoneuronal vulnerability are recapitulated. Results are mainly drawn from the mutant SOD1 mouse model of ALS, and emphasis is placed on early changes that precede the onset of symptoms and the interplay between molecular and electrical processes.


Science, politics, and the play of chance in recent Australian drinking law changes.
Regulating late-night alcohol sales to prevent violence continues to be hotly debated in Australia. From July this year, Queensland required premises to stop serving alcohol (last drinks) by 3 am in entertainment precincts and by 2 am in the rest of the state. The Government made legislative provision for 1 am lockouts in entertainment precincts but at the time of writing has not committed to introducing them. Lockouts, also known as one-way-doors, permit patrons to remain drinking in premises until last drinks but deny entry to new patrons. In Newcastle, New South Wales, lockouts and earlier closing of licensed premises were introduced in 2008. Evidence that these produced large reductions in assault informed the 2014 Sydney restrictions that are currently under review. The global research evidence for last drinks regulations is compelling: trading extensions of as little as one h increase harm, and similarly modest restrictions reduce harm. In contrast, the effectiveness of lockouts, a phenomenon unique to Australasia, is uncertain. The Newcastle, Sydney and Queensland reforms are a stepwise progression in alcohol harm countermeasures, a welcome example of evidence-based public policy. However, the aetiologies of these policy changes were complex. I present accounts of each and offer commentary on the interplay between scientific evidence, public health advocacy, politics, and chance occurrences that preceded these significant changes.


Prokaryotic elongation factor Tu is phosphorylated in vivo.
Covalent modification of proteins by phosphate transfer reactions constitutes a major mechanism of regulation in higher eukaryotes. Recently, phosphorylation of eukaryotic elongation factors has been described. Analysis of Escherichia coli proteins revealed several of them to be phosphorylated. Various lines of evidence lead us to conclude that one of these proteins is identical to elongation factor (EF) Tu, which can be phosphorylated in vivo at one of its threonine residues. Structural analysis showed that one fragment of the phosphorylated EF-Tu is highly resistant to tryptic digestion. Phosphorylation of eubacterial EF-Tu is not restricted to the E. coli factor but could also be demonstrated for Thermus thermophilus HB8 EF-Tu. Overexpression of tufA did not increase the number of EF-Tu molecules to be phosphorylated. This may indicate that a constant but limited amount of EF-Tu is modified, possibly for a specific function. Phosphorylation of EF-Tu could also be demonstrated in vitro. Upon analysis of subcellular fractions the highest kinase activity was found in the ribosomal fraction of E. coli. Protein sequencing of both the in vivo and in vitro phosphorylated protein revealed position 382 as the modified threonine residue.


Hydrodynamic analysis of different thumb positions in swimming.
The aim of the present study was to analyze the hydrodynamic characteristics of a true model of a swimmer hand with the thumb in different positions using numerical simulation techniques. A three-dimensional domain was created to simulate the fluid flow around three models of a swimmer hand, with the thumb in different positions: thumb fully abducted, partially abducted, and adducted. These three hand models were obtained through computerized tomography scans of an Olympic swimmer hand. Steady-state computational fluid dynamics analyses were performed using the Fluent(®) code. The forces estimated in each of the three hand models were decomposed into drag and lift coefficients. Angles of attack of hand models of 0°, 45° and 90°, with a sweep back angle of 0° were used for the calculations. The results showed that the position with the thumb adducted presented slightly higher values of drag coefficient compared with thumb abducted positions. Moreover, the position with the thumb fully abducted allowed increasing the lift coefficient of the hand at angles of attack of 0° and 45°. These results suggested that, for hand models in which the lift force can play an important role, the abduction of the thumb may be better, whereas at higher angles of attack, in which the drag force is dominant, the adduction of the thumb may be preferable. Key pointsNumerical simulation techniques can provide answers to problems which have been unobtainable using experimental methods.The computer tomography scans allowed the creation of a complete and true digital anatomic model of a swimmer hand.The position with the thumb adducted presented slightly higher values of drag coefficient than the positions with the thumb abducted.The position with the thumb fully abducted allowed increasing the lift coefficient of the hand at angles of attack of 0 and 45 degrees.For hand positions in which the lift force can play an important role the abduction of the thumb may be better whereas at higher angles of attack, in which the drag force is dominant, the adduction of the thumb may be preferable for swimmers.


Cortisol inhibits the synthesis of insulin-like growth factor-binding protein-5 in bone cell cultures by transcriptional mechanisms.
Glucocorticoids inhibit the synthesis of insulin-like growth factor-binding protein-5 (IGFBP-5) in osteoblasts, but the mechanisms involved are unknown. IGFBP-5 stimulates bone cell growth, and its inhibition by glucocorticoids may be relevant to the action of this binding protein on bone formation. We tested the effects of cortisol on IGFBP-5 expression in cultures of osteoblast-enriched cells from fetal rat calvariae (Ob cells). Cortisol decreased IGFBP-5 polypeptide levels in the extracellular matrix and caused a time- and dose-dependent decrease in IGFBP-5 mRNA. IGFBP-5 transcripts were markedly decreased by cycloheximide, and further suppressive effects of cortisol could not be determined. Cortisol did not modify the decay of IGFBP-5 mRNA in transcriptionally arrested Ob cells. Cortisol decreased IGFBP-5 hnRNA, the rate of IGFBP-5 transcription, and the activity of the murine IGFBP-5 promoter by 35% in transient transfection experiments. Deletion analysis showed that the region responsive to cortisol is from base pairs -70 to +22, and E-box-binding proteins or c-Myb-related nuclear factors may be involved in its regulation. In conclusion, cortisol inhibits IGFBP-5 transcription in Ob cells through the Myb-binding domain. This effect may be partly responsible for the effect of glucocorticoids on bone formation.


Tonal vocalizations in the red wolf (Canis rufus): potential functions of nonlinear sound production.
The purpose of this study is to further understanding of the function of nonlinear vocalizations in red wolves (Canis rufus) by examining the acoustic, structural, and contextual characteristics of nonlinear sounds as compared to linear sounds. Video recordings of captive wolves from a breeding facility were analyzed. The acoustic nature of sound units was consistent with that of other social canids. The sound units included high-frequency squeaks (2600-9500 Hz) and low-frequency wuhs (160-1600 Hz) occurring either as separate units or in combination as nonlinear units (squeak-wuh frequency jumps, biphonations, squeaks with sidebands) and frequency jumps within squeaks. These low-amplitude sounds occurred in trains of 1-30 units that were classified as squeak vocalizations (49%), wuh vocalizations (19%), and nonlinear vocalizations (any combination including one or more nonlinear units, 32%). Nonlinear vocalizations transitioned directionally from high-frequency units to mixed-frequency units which has implications for the study of sound production and function. Wolves squeaked most often when oriented toward others, implying a solicitation function, while wuh vocalizations were more common during social interactions. Nonlinear vocalizations occurred most often during penmate-play or when oriented toward neighbors, indicating that nonlinear sound production may signal an increase in arousal.


Reverie and interpretation.
The analyst's reverie experience constitutes an indispensable avenue to the understanding and interpretation of the transference-countertransference and yet is perhaps the dimension of the analyst's experience that feels least worthy of scrutiny. Reverie takes the most mundane, personal, and private of shapes, often involving the minutiae of everyday life. Although the analyst's reveries are personal psychological events, I view them as unconscious intersubjective constructions generated by analyst and analysand. Three analytic sessions are discussed to illustrate the ways in which reveries are experienced as well as the process by which the analyst attempts to make use of this aspect of his or her experience.


[Efficacy of Modified Acupuncture Method at Renying (ST 9) for Patients with Cervical Spondylosis of Vertebral Artery Type and Its Impact on Velocity of Cervical Blood Flow].
To observe the clinical efficacy of modified acupuncture at Renying point (ST 9) for patients with cervical spondylosis of vertebral artery type and its influence on velocity of cervical blood flow. Fifty-nine cases of vertebral artery type cervical spondylosis were randomly divided into control group (n=30) and treatment group (n=29). Both groups were acupunctured at ST 9, with routine acupuncture technique used in the control group and modified technique in the treatment group, respectively. All cases received two courses of treatment, each course covered consecutive 6 once-per-day treatments. Before and after treatment, transcranial Doppler (TCD) was used to measure the systolic peak blood flow velocity (Vs) of left vertebral artery (LVA), right vertebral artery (RVA) and basilar artery (BA), and the scores of "cervical vertigo symptoms and functional assessment scale" (CVSFAS) were also assessed, separately. CVSFAS scoring, Vs of LVA, RVA and BA after treatment showed significant improvement compared with those before treatment (P<0.01, P<0.05). The efficacy of the treatment group in the above mentioned indexes was superior to that of the control group (P<0.05). The total effective rate of the treatment group was 93.1% (27/29), superior to 70.0% (21/30) of the control group (P<0.05). The modified acupuncture method at ST 9 is clinically effective in the treatment of cervical spondylosis of vertebral artery type via increasing the Vs of vertebral-basilar artery, improving the local blood circulation and relieving pain.


A trial of thyroxine in acute renal failure.
A trial of thyroxine in acute renal failure. Acute renal failure (ARF) remains a serious medical problem with a high mortality rate. Efforts to shorten the course of ARF might reduce this mortality. Since thyroxine has been shown in experimental models to shorten the course of ARF, we designed a trial to determine if a defined course of thyroxine would alter the course or change the mortality of clinical ARF. A prospective, randomized, placebo-controlled, double-blind trial of thyroxine was carried out in patients with ARF. End points were the percentage requiring dialysis, the percentage recovering renal function, time to recovery, and mortality. Fifty-nine patients were randomized to receive either thyroxine or placebo. The groups were well matched in terms of basal and entry creatinines, age, sex, APACHE II scores at entry, and percentage oliguric. Baseline thyroid functions, including T3, T4, rT3, and thyroid stimulating hormone (TSH) levels, were equal between the two groups and typical of patients with euthyroid sick syndrome. Thyroxine resulted in a progressive and sustained suppression of TSH levels in the treated group, but had no effect on any measure of ARF severity. Mortality was higher in the thyroxine group than the control group (43 vs. 13%) and correlated with suppression of TSH. In contrast to the beneficial effects seen in experimental ARF, thyroxine has no effect on the course of clinical ARF and could have a negative effect on outcome through prolonged suppression of TSH. Critically ill euthyroid sick patients should not be replaced with thyroid hormone.


Urinary retention in hospitalized elderly women.
Unrecognized urinary retention may be a factor in the development of recurrent urinary tract infections, urinary incontinence, bladder dysfunction, and upper urinary tract disease. Because urinary retention is often asymptomatic in elderly women, with amounts of up to 1,500 mL retained in the bladder often causing little or no discomfort, nurses need to have a high index of suspicion about its occurrence. A post-void residual is the best way of determining the presence of urinary retention. The goal of treatment for urinary retention is bladder decompression via catheterization followed by voiding trials and determination of residual volumes.


Effects of increased payment for ventilation tube insertion on decision making for paediatric otitis media with effusion.
The National Health Insurance (NHI) in Taiwan raised the physician fee for myringotomy with ventilation tube insertion (VTI) from $61.5 to $117.6 in July 2004. This study aimed to evaluate if the increased payment affected the decision making of physicians. This study is a retrospective analysis by using NHI databank in Taiwan. All children less than 12 years old who underwent VTI from 1 July 2003 to 30 June 2006 were included. Waiting time and case numbers before and after the increased VTI payment were compared. The waiting time between public and private hospitals was also examined. From the 7408 cases evaluated, there was no difference in waiting time before and after the raise of VTI payment, and no difference within each year group. The case number of VTI increased significantly after the increase in VTI payment (P < 0.05). The waiting time of VTI performed in private hospitals was shorter than that in public hospitals (P = 0.0001). The waiting time of VTI for children with otitis media with effusion (OME) has not been shortened after the increase in VTI payment. Waiting time in private hospitals is shorter than that in public hospitals. Increased payment for VTI has no effect on the physicians' decision making regarding to waiting time for children with OME in Taiwan.


Metal release from heat-treated orthodontic archwires.
Stainless steel and cobalt-chromium orthodontic archwires were subjected to an immersion corrosion test. Wires in the as-received state and wires subjected to a 1-min heat treatment at different temperatures were tested. Iron from the stainless steel and cobalt from the cobalt-chromium product were analyzed in artificial saliva after 1 week of immersion. Both products were analyzed for nickel. The results showed that the cobalt-chromium wire in the as-received state released more metals than the stainless steel. The metal release from the stainless steel wire increased rapidly when subjected to 400 degrees C or higher. For the cobalt-chromium product the increase started at about 500 degrees C. At temperatures above 500 degrees C the release of metals was 15 to 60 times higher than the lowest values. The present results should be considered in procedures involving application of heat to orthodontic wires.


Facile and Eco-Friendly Fabrication of Colored and Bioactive Silk Materials Using Silver Nanoparticles Synthesized by Two Flavonoids.
Recently, there has been an increasing tendency towards the functionalization of silk using silver nanoparticles (AgNPs) to inhibit bacterial multiplication and disease spread. Considering environmental factors and sustainable development, the preparation of AgNPs using natural extracts is becoming a research hotspot. This study aims at fabricating colored and bioactive silk fabric using AgNPs synthesized by two representative flavonoids (quercetin and rutin). The effects of pH, temperature, and flavonoid concentration on the yield and particle size of AgNPs were studied. The color features and functionalities of the AgNPs-treated silk were also evaluated. The results showed that the AgNPs synthesized by quercetin were generated faster but displayed poorer size uniformity than those prepared by rutin. The as-prepared AgNPs showed good stability. The AgNPs prepared by rutin displayed a more uniform distribution on silk than those synthesized by quercetin. The antibacterial activity of AgNPs-treated silk remained over 90% against E. coli and S. aureus even after 30 washing cycles. The antioxidant activity of the treated silk gradually decreased during washing. The present research proposes a facile and eco-friendly method for the preparation of AgNPs-coated silk material using flavonoids, which can serve as hygiene-related and medical textile materials.


Functional abnormalities of the cervical cord and lower medulla and their effect on pain: observations in chronic pain patients with incidental mild Chiari I malformation and moderate to severe cervical cord compression.
Abnormalities of central sensory processing may play a role in the pathogenesis of chronic pain. The Chiari I malformation is a congenital hindbrain anomaly characterized by protrusion of the cerebellar tonsils into the upper cervical canal, with variable effects on the lower brain stem and cervical cord. The purpose of this study was to compare sensory function and pain among patients with chronic pain who had these disorders incidentally diagnosed, to assess the effect on pain in these patients in comparison with those without central nervous system disease. Retrospective study in which pain, mood, and sensory function in 32 patients with chronic pain who had mild Chiari I malformation were compared with that in 53 patients with chronic pain who had moderate to severe compression of the cervical spinal cord and 52 patients with chronic pain who had no apparent central nervous system disorder. Data had been collected previously as part of standard clinical assessments, including clinical neurological examinations, quantitative sensory testing, pain drawings, and psychometric testing with the Symptom Checklist 90. All subjects were patients of a hospital-based pain management practice who had been accepted for treatment over a 5-year period. Both the Chiari I and cervical compression groups had long tract signs evident on clinical neurological examination. Quantitative sensory testing indicated elevations in the trigeminal territory among patients with Chiari I malformation and on the neck, hands, and feet in both the Chiari I and cervical compression groups. The extent of pain and mood disturbance was greatest in the Chiari I group and least in the group with no central nervous system disorder. Complex regional pain syndrome, fibromyalgia, and temporal mandibular joint disorder were more common among the Chiari I malformation group than among the other groups. Quantitative sensory analysis indicates sensory dysfunction associated with Chiari I malformation and cervical cord compression. The pattern of sensory abnormality is consistent with medullary dysfunction among the patients with Chiari I malformation and cervical cord dysfunction among cord compression patients. There were differences in the types and extent of pain and the associated disorders of mood observed among the cohorts defined above. These differences may be partly due to the presence and location of central sensory dysfunction.


Decree No. 17898-S of 2 December 1987.
This Decree, which is aimed at guaranteeing health care for all the people of Costa Rica, recognizes the right of persons insured by the State to receive, without direct payment, services to protect their health in the facilities of the Costa Rica Social Security Fund. A person insured by the State is defined as a user of health services not included in any of the schemes, categories, or agreements of the Fund and who cannot pay for health services. Further provisions of the Decree set forth rules on determining who is eligible to receive health services and the financing of such services, among other things.


Plasmonic micropipe spectral filters in mid-infrared.
Multispectral analyzers based on nanostructured plasmonic spectral filters can potentially find a wide range of applications. However, spectral filters based on the widely reported microhole or ring arrays suffer from relatively wide filtering bands, resulting in a relatively low spectral resolution. In this work, we fabricate high-performance spectral filters based on vertically standing micropipes on a silver film. An infrared spectral microscope is used to investigate the properties of these micropipe spectral filters. The results indicate that the micropipe spectral filters have a full width at half-maximum ∼5 times smaller than the microhole filters at the same wavelength. Micropipe spectral filters are expected to significantly improve the spectral resolution of multispectral analyzers.


Effects of vascular endothelial growth factors and their receptors on megakaryocytes and platelets and related diseases.
It is well known that vascular endothelial growth factors (VEGFs) and their receptors (vascular endothelial growth factor receptors, VEGFRs) are expressed in different tissues, and VEGF-VEGFR loops regulate a wide range of responses, including metabolic homeostasis, cell proliferation, migration and tubuleogenesis. As ligands, VEGFs act on three structurally related VEGFRs (VEGFR1, VEGFR2 and VEGFR3 [also termed FLT1, KDR and FLT4, respectively]) that deliver downstream signals. Haematopoietic stem cells (HSCs), megakaryocytic cell lines, cultured megakaryocytes (MKs), primary MKs and abnormal MKs express and secrete VEGFs. During the development from HSCs to MKs, VEGFR1, VEGFR2 and VEGFR3 are expressed at different developmental stages, respectively, and re-expressed, e.g., VEGFR2, and play different roles in commitment, differentiation, proliferation, survival and polyplodization of HSCs/MKs via autocrine, paracrine and/or even intracrine loops. Moreover, VEGFs and their receptors are abnormally expressed in MK-related diseases, including myeloproliferative neoplasms, myelodysplastic syndromes and acute megakaryocytic leukaemia (a rare subtype of acute myeloid leukaemia), and they lead to the disordered proliferation/differentiation of bone marrow cells and angiogenesis, indicating that they are closely related to these diseases. Thus, targeting VEGF-VEGFR loops may be of potential therapeutic value.


Closed-Loop Oxygen Control Using a Novel Nasal High-Flow Device: A Randomized Crossover Trial.
Oxygen administration is recommended for patients with hypoxemia to achieve a target [Formula: see text] range. Strategies to achieve this in clinical practice are suboptimal. We investigated automatic oxygen titration using a novel nasal high-flow device with closed-loop oxygen control. The objective of this proof-of-concept study was to determine whether closed-loop control was able to respond to desaturation and subsequent recovery in a controlled laboratory-based environment. We conducted a single-blind randomized crossover trial in adults with chronic respiratory disease who had a resting [Formula: see text] ≥ 92% and desaturated to < 90% during a 6-min walk test (6MWT). Nasal high-flow was administered during a 6MWT and a subsequent 10-min rest period with either room air, a fixed concentration of 28% oxygen, or oxygen titrated automatically using closed-loop control. The study involved 42 subjects. Closed-loop control maintained [Formula: see text] within the target range of 92-96% for a mean (SD) duration of 54.4 ± 30.1% of the 6MWT and 67.3 ± 26.8% of the recovery period. The proportion of time spent with an [Formula: see text] in the target range during the 6MWT was significantly greater for closed-loop control compared to room air, with a difference of 26.0% (95% CI 17.7-34.2, P < .001); this proportion of time was not significantly different compared to the fixed concentration of 28% oxygen, with a difference of -8.2% (95% CI -16.5 to 0.1, P = .052). The proportion of time spent in the target range during the rest period was significantly greater compared to 28% oxygen, with a difference of 19.3% (95% CI 8.9-29.7, P < .001); this proportion of time was not significantly different compared to room air, with a difference of -9.3% (95% CI -19.7 to 1.0, P = .08). This study provides proof-of-concept evidence that the novel nasal high-flow device with closed-loop control can respond to changes in [Formula: see text] outside a target saturation range using a model of exercise-induced desaturation and subsequent recovery.


Developing an interprofessional research infrastructure at a mid-sized liberal arts university.
This Interprofessional Education and Practice (IPEP) Guide describes the various mechanisms used to grow and support interprofessional research and scholarship at a mid-sized liberal arts university. The guide illustrates a creative, multi-stakeholder approach to integrating interprofessional education into university departments and programs and offers suggestions for establishing a research infrastructure that centers interprofessional scholarly engagement and is aligned with the institution's missions and values. Faculty and higher education practitioners are provided with key takeaways for crafting an internal grants program to achieve these goals.


Distribution networks and electrically controllable couplers for integrated optics.
The power distribution as a function of propagation distance in a network of coupled optical waveguides is determined for several interesting cases. An electrically controllable coupler is proposed and analyzed in detail. High efficiency coupling and decoupling between two optical guides can be accomplished with the use of an electrooptically generated dynamic channel, of finite length, located in between the two guides.


A Molecular Hero Suit for In Vitro and In Vivo DNA Nanostructures.
Precise control of DNA base pairing has rapidly developed into a field full of diverse nanoscale structures and devices that are capable of automation, performing molecular analyses, mimicking enzymatic cascades, biosensing, and delivering drugs. This DNA-based platform has shown the potential of offering novel therapeutics and biomolecular analysis but will ultimately require clever modification to enrich or achieve the needed "properties" and make it whole. These modifications total what are categorized as the molecular hero suit of DNA nanotechnology. Like a hero, DNA nanostructures have the ability to put on a suit equipped with honing mechanisms, molecular flares, encapsulated cargoes, a protective body armor, and an evasive stealth mode.


Plasticizer effect and comparative evaluation of cellulose acetate and ethylcellulose-HPMC combination coatings as semipermeable membranes for oral osmotic pumps of naproxen sodium.
The objective of this study was to compare the performance of cellulose acetate (CA) and ethylcellulose (EC)-HPMC combination coatings as semipermeable membranes (SPMs) for osmotic pump tablets (OPTs) of naproxen sodium (NPS) so as to deliver a constant, predetermined amount of drug in solution form over a fixed span of time, independent of external environmental conditions. Osmotic pump tablets were designed with different coating variables and optimized in terms of nature of plasticizer, membrane thickness, and orifice diameter. The effect of insertion of an inner microporous film around the NPS core to minimize deformation of the SPM due to peristaltic movement of the gut was also studied. Osmotic pump tablets composed of membranes with water-soluble plasticizer, propyleneglycol (PG), released drug mainly through diffusion, whereas those designed with CA and EC-HPMC (4:1) coats containing water-insoluble plasticizer, castor oil, released their contents by perfect zero-order kinetics over a prolonged period of time, though the average release rate that could be achieved with the EC-HPMC (4:1) membrane was only about half the rate achieved with the CA membrane for the same membrane thickness. Release rates for both the membranes decreased with increasing membrane thickness and were found to be independent of orifice diameter, agitation intensity, and pH of the dissolution medium.


Oxidative stress, renal anemia, and its therapies: is there a link?
In chronic kidney disease, anemia and oxidative stress are common features and both are involved in increasing morbidity and mortality. However, their relationship is still a matter of debate. This article is a review of published data and our experience and is intended to debate the pro and contra arguments concerning renal anemia and its 2 main therapeutic approaches, that are, erythropoietin and intravenous iron supplementation, as additional causes of oxidative stress in end-stage renal disease patients. To date, it seems more likely that renal anemia itself is the main contributor, and intravenous iron further enhances oxidative stress associated with chronic kidney disease. Future randomized prospective trials, with "hard" clinical end-points, are needed to establish the real effect of biochemical pro-oxidative changes on patient's outcome.


Apatinib plus icotinib in treating advanced non-small cell lung cancer after icotinib treatment failure: a retrospective study.
Treatment failure frequently occurs in patients with epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC) who respond to EGFR tyrosine kinase inhibitors initially. This retrospective study tried to investigate the efficacy and safety of apatinib plus icotinib in patients with advanced NSCLC after icotinib treatment failure. This study comprised 27 patients with advanced NSCLC who had progressed after icotinib monotherapy. Initially, patients received oral icotinib (125 mg, tid) alone. When the disease progressed, they received icotinib plus apatinib (500 mg, qd, orally). Treatment was continued until disease progression, unacceptable toxicity or consent withdrawal. Followed up to December 2016, the median time of combined therapy was 7.47 months, and eight of 27 patients were dead. The median overall survival was not reached, and median progression-free survival (PFS) was 5.33 months (95% CI, 3.63-7.03 months). Moreover, the objective response rate (ORR) was 11.1%, and the disease control rate (DCR) was 81.5%. A total of 14 patients received combined therapy as the second-line treatment, and the ORR and DCR were 7.1% and 78.6%, respectively; 13 patients received drugs as the third- or later-line treatment, with an ORR and a DCR of 15.4% and 84.6%, respectively. In addition, 11 patients experienced icotinib monotherapy failure within 6 months with median PFS of 7.37 months, and 16 patients had progression after 6 months with median PFS of 2.60 months. The common drug-related toxic effects were hypertension (44.4%) and fatigue (37.0%). Apatinib plus icotinib is efficacious in treating patients with advanced NSCLC after icotinib treatment failure, with acceptable toxic effects.


Impact of observers' experience and training on reliability of observations for a manual handling task.
Observation reliability (agreement percentage and kappa coefficients) for six experienced ergonomists and six untrained participants was computed. Participants were first tested after a training session and 1 week later after an additional practice session. Two formats were used: free practice and directed exercise. Reliability was tested for 17 variables and 20 sequences using photographic and video supports. The participants were asked to indicate whether they were confident about their answer, to rate this confidence on a scale of 1 to 10, and when the confidence rating was below 8, to provide a reason for this. Experience and additional practices had no clear impact on reliability, which was excellent overall. The main reason given was that the event to be observed took place at the borderline between two classes. The observers' rating on the scale appeared to be tied to the subsequent reliability computed. The use of a confidence scale appeared to be a useful tool for forecasting observation problems.


Analysis of fine-needle aspiration biopsies by flow cytometry in kidney transplant patients.
Peripheral blood lymphocyte (PBL) analysis by flow cytometry has been inconsistently reported as an adjunctive method for diagnosing acute kidney transplant rejection. However, there is good evidence that lymphocytes infiltrating renal grafts differ from those found at the peripheral level. We hypothesized that the study of aspiration biopsy samples in conjunction with PBL by flow cytometry would enable us to diagnose acute rejection crisis reliably. Lymphocytes from PBL and aspiration biopsies of kidney transplant patients were analyzed. Fifty-one stable patients, rejection-free for the first 6 months, were studied on day 7 and day 30 after transplantation and were compared with 32 patients with 40 acute rejection episodes. Significant differences were observed for several lymphocyte subpopulations on aspiration biopsy samples comparing stable patients with rejection patients. In contrast, PBL analysis was not helpful in differentiating the two groups of patients. By combining the expression of several activation markers inside the graft with CD3DR and CD3CD25 aspiration biopsy to peripheral blood ratios, we obtained very good values for sensitivity and specificity-83.9% and 90.5%, respectively. The positive predictive value for rejection among dysfunctional grafts reached 85.8%. Flow cytometry study of aspiration biopsy samples of kidney transplant patients is a reliable and powerful method to diagnose acute rejection episodes, although it is needed to consider several lymphocyte phenotypes; cytofluorometric analysis of PBL is important because it provides graft-infiltrating cell to peripheral blood lymphocyte ratios. This safe and rapid test may significantly improve the management of kidney transplant patients.


Luminal surfaces of fetal rat alveolar type II and Clara lung cells react with antibody to Heymann nephritis antigen.
We have used affinity purified antibody, which reacts with the renal antigen gp600, to examine the immunoreactivity of pulmonary cells in the quick frozen lung tissue of fetal rats. On immunoelectron microscopy, we found that the reaction was specifically localized to the luminal surfaces of Clara cell and, as previously reported, to alveolar type II cell (ATII) membranes. No immunoreaction was seen on or in type I cells, endothelial cells or any other lung or blood cell. These studies suggest that the anti-gp600 immunoselection can be used as a marker to identify and quantify Clara and ATII cells in rat lung tissue.


Platelet monoamine oxidase type B, MAOB intron 13 and MAOA-uVNTR polymorphism and symptoms of post-traumatic stress disorder.
Post-traumatic stress disorder (PTSD), a disorder that develops following exposure to traumatic experience(s), is frequently associated with agitation, aggressive behavior and psychotic symptoms. Monoamine oxidase (MAO) degrades different biogenic amines and regulates mood, emotions and behavior, and has a role in the pathophysiology of various neuropsychiatric disorders. The aim of the study was to investigate the association between different symptoms occurring in PTSD [PTSD symptom severity assessed by the Clinician Administered PTSD Scale (CAPS), agitation and selected psychotic symptoms assessed by the Positive and Negative Syndrome Scale (PANSS)] and platelet MAO-B activity and/or genetic variants of MAOB rs1799836 and MAOA-uVNTR polymorphisms in 249 Croatian male veterans with PTSD. Our study revealed slightly higher platelet MAO-B activity in veterans with PTSD with more severe PTSD symptoms and in veterans with agitation, and significantly higher platelet MAO-B activity in veterans with more pronounced psychotic symptoms compared to veterans with less pronounced psychotic symptoms. Platelet MAO-B activity was associated with smoking but not with age. Genetic variants of MAOB rs1799836 and MAOA-uVNTR were not associated with agitation and selected psychotic symptoms in veterans with PTSD. A marginally significant association was found between MAOB rs1799836 polymorphism and severity of PTSD symptoms, but it was not confirmed since carriers of G or A allele of MAOB rs1799836 did not differ in their total CAPS scores. These findings suggest an association of platelet MAO-B activity, but a lack of association of MAOB rs1799836 and MAOA-uVNTR, with selected psychotic symptoms in ethnically homogenous veterans with PTSD.


Seasonal changes in testicular size, plasma testosterone concentration and body weight in captive flying foxes (Pteropus poliocephalus and P. scapulatus).
Adult male flying foxes Pteropus poliocephalus and P. scapulatus were captured in south-east Queensland and kept in outdoor enclosures. Testicular size (TS), plasma testosterone concentrations (PTC) and body weight (BW) were measured over 1-year periods. Testicular recrudescence in P. poliocephalus began before the summer solstice and TS was greatest during mid-March (autumn) and lowest from July to September. Large increases in PTC were observed in all individuals approximately 1 month after the peak in TS. BW also increased around the time of the mating season, changes being correlated significantly with changes in TS. Mating occurred between April and June, and births from late October to late November. In P. scapulatus, TS was greatest in the spring (October) and least in the autumn (February to May); PTC fluctuated throughout the year in this species but, unlike P. poliocephalus, did not show a single large increase in the mating season. BW showed a similar seasonal pattern to that seen in P. poliocephalus, being greatest at the time of greatest TS. Mating occurred in October to November, and births in autumn. In captivity, in outdoor enclosures, these species maintained the seasonal reproductive patterns observed in the wild. The 2 species respond differently to the same environmental cues in terms of regulation of the timing of their breeding seasons.


In Situ Estimates of Variable Plant Resistance to Water Flux in Ilex opaca Ait.
Xylem pressure potentials and stomatal diffusion resistances were measured in the field in Ilex opaca Ait. during days which differed in temperature and vapor pressure deficit. Water flux into leaves was calculated by combining the field data with laboratory determinations of the relation between tissue water deficit and water potential. Estimates of apparent plant resistance were then calculated from fluxes and differences between soil water potential and xylem tension. The resistance depended strongly on water flux, dropping by a factor of over 7 from low to high water flow rates. This extends the generality of variable plant resistances measured in controlled environment studies to I. opaca as it occurs naturally in the field. The relation of apparent plant resistance to water flux as estimated in this study can be useful in simulation models which calculate water uptake to leaves as a flux driven by a difference in soil and leaf water potentials across a resistance between the bulk soil and the leaf.


The SET-2/SET1 histone H3K4 methyltransferase maintains pluripotency in the Caenorhabditis elegans germline.
Histone H3 Lys 4 methylation (H3K4me) is deposited by the conserved SET1/MLL methyltransferases acting in multiprotein complexes, including Ash2 and Wdr5. Although individual subunits contribute to complex activity, how they influence gene expression in specific tissues remains largely unknown. In Caenorhabditis elegans, SET-2/SET1, WDR-5.1, and ASH-2 are differentially required for germline H3K4 methylation. Using expression profiling on germlines from animals lacking set-2, ash-2, or wdr-5.1, we show that these subunits play unique as well as redundant functions in order to promote expression of germline genes and repress somatic genes. Furthermore, we show that in set-2- and wdr-5.1-deficient germlines, somatic gene misexpression is associated with conversion of germ cells into somatic cells and that nuclear RNAi acts in parallel with SET-2 and WDR-5.1 to maintain germline identity. These findings uncover a unique role for SET-2 and WDR-5.1 in preserving germline pluripotency and underline the complexity of the cellular network regulating this process.


Does cross-sex transmission increase the severity of polio infection? A study of multiple family cases.
Previous studies have suggested that transmission of measles virus from the opposite sex increases the severity of infection; however, the role of gender in the transmission of other infections has not been examined. Multiple polio cases within a family usually occur simultaneously, and are therefore likely to be secondary to a common subclinical index case. The few clinical polio cases that appear much later than any other clinical case are likely to be tertiary cases. If cross-sex transmission increases the severity of infection then multiple polio cases would tend to affect the same sex, i.e. the opposite sex to that of the subclinical index case. In order to assess this phenomenon we identified 6345 records of individuals hospitalized with poliomyelitis in Copenhagen between 1919 and 1953. The severity and gender of suspected secondary and tertiary cases were analysed among all multiple household cases. Overall, 70% of the 133 sibling pairs having polio simultaneously were same-sex pairs, which differed significantly from the expected 52% (chi2 = 9.1; p < 0.01). Tertiary cases with exposure to the opposite sex were more likely to be paralytic than cases with exposure to the same sex [relative risk (RR) = 2.86 (95% confidence interval 1.08-7.58)1. In families with adult polio cases, possible tertiary cases were more common among fathers (7/24) than among mothers (1/35) [RR = 10.21 (1.34-77.72)]. We examined whether the excess of male polio cases was more pronounced in small families where the mother would play a relatively larger role in disease transmission and found that the male:female excess decreased with increasing birth order (p = 0.02) and family size (p = 0.09). The strong tendency towards same-sex pairs in 2-case families suggests that gender plays an important role in the severity of polio infection. Cross-sex transmission may increase the severity of polio and mothers may contribute to the higher prevalence of polio cases among boys.


Erythrophagocytosis in a patient with B-cell acute lymphoblastic leukemia with t(12;21) (p13.2; q22.1); ETV6-RUNX1: Case report and review of the literature.
Erythrophagocytosis (EP) is extremely rare in de novo acute lymphoblastic leukemia (ALL). We document a rare case, which in addition, showed extensive blast vacuolization. A detailed literature review has also been incorporated with the aim of unraveling the prognostic import of our morphological observations if any. A five-year-old male presented with fever and progressive pallor for 1 month. He had hepatosplenomegaly and bicytopenia. Peripheral smear examination showed 43% blasts. Nuclear and cytoplasmic vacuolations were seen in 75% blasts and EP in 4% blasts. The blasts showed block positivity on periodic acid-Schiff (PAS) stain. Marrow aspirate smears showed 58% blasts displaying a similar morphology. Flow cytometry showed features of a common acute lymphoblastic leukemia antigen (CALLA) positive B-cell ALL with aberrant, dim CD 33 expression in 53.4% of the gated blasts. Fluorescence in situ hybridization showed translocation (12; 21) (p13;q22). The patient responded well to standard induction therapy. To conclude, EP is rarely seen in de novo ALL and is associated with a favorable translocation, t(12;21).


Mechanisms of proximal tubule sodium transport regulation that link extracellular fluid volume and blood pressure.
One-hundred years ago, Starling articulated the interdependence of renal control of circulating blood volume and effective cardiac performance. During the past 25 years, the molecular mechanisms responsible for the interdependence of blood pressure (BP), extracellular fluid volume (ECFV), the renin-angiotensin system (RAS), and sympathetic nervous system (SNS) have begun to be revealed. These variables all converge on regulation of renal proximal tubule (PT) sodium transport. The PT reabsorbs two-thirds of the filtered Na(+) and volume at baseline. This fraction is decreased when BP or perfusion pressure is increased, during a high-salt diet (elevated ECFV), and during inhibition of the production of ANG II; conversely, this fraction is increased by ANG II, SNS activation, and a low-salt diet. These variables all regulate the distribution of the Na(+)/H(+) exchanger isoform 3 (NHE3) and the Na(+)-phosphate cotransporter (NaPi2), along the apical microvilli of the PT. Natriuretic stimuli provoke the dynamic redistribution of these transporters along with associated regulators, molecular motors, and cytoskeleton-associated proteins to the base of the microvilli. The lipid raft-associated NHE3 remains at the base, and the nonraft-associated NaPi2 is endocytosed, culminating in decreased Na(+) transport and increased PT flow rate. Antinatriuretic stimuli return the same transporters and regulators to the body of the microvilli associated with an increase in transport activity and decrease in PT flow rate. In summary, ECFV and BP homeostasis are, at least in part, maintained by continuous and acute redistribution of transporter complexes up and down the PT microvilli, which affect regulation of PT sodium reabsorption in response to fluctuations in ECFV, BP, SNS, and RAS.


Dexmedetomidine attenuates H2O2-induced neonatal rat cardiomyocytes apoptosis through mitochondria- and ER-medicated oxidative stress pathways.
Dexmedetomidine (DEX), an α2 adrenoceptor agonist, has sedative and analgesic properties and myocardial protective effects. However, the mechanism underlying the protective effects of DEX on the myocardium remain unclear. The present study aimed to determine whether DEX serves an important role on cardioprotection through the endoplasmic reticulum (ER)‑ and mitochondria‑mediated apoptosis signaling pathways. Neonatal rat cardiomyocytes (NRCMs) were cultured and divided four groups: i) Normal culture medium with 10% fetal bovine serum (control group); ii) H2O2 at 500 µM (H2O2 group); iii) DEX at 5 µM (DEX group); and iv) H2O2 plus DEX (H2O2 + DEX group). The levels of apoptosis and oxidative stress of NRCMs were investigated by ELISA, western blotting, flow cytometry and cell immunofluorescence. DEX significantly suppressed H2O2‑induced apoptosis, and increased activity of caspases 3, 8 and 9 of NRCMs. DEX inhibited mitochondria‑mediated oxidative stress and apoptosis, as evidenced by decreased levels of reactive oxygen species and lactic dehydrogenase, alleviated mitochondrial membrane potential depolarization, and increased Bcl‑2‑associated X protein/B‑cell lymphoma 2 ratio. In addition, DEX decreased the activity of caspase 12, and the expression levels of glucose‑regulated protein 78 kDa and serine/threonine‑protein kinase/endoribonuclease IRE1, three major signaling molecules involved in the ER stress‑mediated apoptosis pathway. Preventive treatment with DEX alleviates cardiomyocyte against H2O2‑induced oxidative stress injury through attenuating the mitochondria‑ and ER‑mediated apoptosis pathways.


A modified technique for descemet membrane stripping automated endothelial keratoplasty to minimize endothelial cell loss.
In an attempt to enhance postoperative survival of donor endothelium, the conventional technique for Descemet membrane stripping automated endothelial keratoplasty (DSAEK) was modified using the prototype of a glide specially designed to facilitate graft delivery and minimize surgical trauma. Instead of using the so-called taco technique, the Busin glide is loaded with the donor lamella, and a microincision forceps is inserted into a temporal side entry and passed across the anterior chamber, exiting through a nasal clear cornea tunnel to grab the graft and drag it into the eye. In 10 patients who underwent DSAEK, mean (SD) postoperative endothelial cell loss was 20.0% (2.6%) at 6 months, 23.5% (2.8%) at 12 months, and 26.4% (2.7%) at 18 to 24 months. Reduced trauma to the graft using our modified technique limits endothelial cell loss after DSAEK to the level recorded after conventional penetrating keratoplasty (PK).


The Axenfeld-Rieger Syndrome Gene FOXC1 Contributes to Left-Right Patterning.
Precise spatiotemporal expression of the Nodal-Lefty-Pitx2 cascade in the lateral plate mesoderm establishes the left-right axis, which provides vital cues for correct organ formation and function. Mutations of one cascade constituent PITX2 and, separately, the Forkhead transcription factor FOXC1 independently cause a multi-system disorder known as Axenfeld-Rieger syndrome (ARS). Since cardiac involvement is an established ARS phenotype and because disrupted left-right patterning can cause congenital heart defects, we investigated in zebrafish whether foxc1 contributes to organ laterality or situs. We demonstrate that CRISPR/Cas9-generated foxc1a and foxc1b mutants exhibit abnormal cardiac looping and that the prevalence of cardiac situs defects is increased in foxc1a-/-; foxc1b-/- homozygotes. Similarly, double homozygotes exhibit isomerism of the liver and pancreas, which are key features of abnormal gut situs. Placement of the asymmetric visceral organs relative to the midline was also perturbed by mRNA overexpression of foxc1a and foxc1b. In addition, an analysis of the left-right patterning components, identified in the lateral plate mesoderm of foxc1 mutants, reduced or abolished the expression of the NODAL antagonist lefty2. Together, these data reveal a novel contribution from foxc1 to left-right patterning, demonstrating that this role is sensitive to foxc1 gene dosage, and provide a plausible mechanism for the incidence of congenital heart defects in Axenfeld-Rieger syndrome patients.


Persistent organic pollutants in four bivalve species from Svalbard waters.
Organochlorine compounds (OC) were determined in Arctic bivalves (Mya truncata, Serripes groenlandicus, Hiatella arctica and Chlamys islandica) from Svalbard with regard to differences in geographic location, species and variations related to their size and age. Higher chlorinated polychlorinated biphenyls (PCB 101-PCB 194), chlordanes and α-hexachlorocyclohexane (α-HCH) were consistently detected in the bivalves and PCBs dominated the OC load in the organisms. OC concentrations were highest in Mya truncata and the lowest in Serripes groenlandicus. Species-specific OC levels were likely related to differences in the species' food source, as indicated by the δ(13)C results, rather than size and age. Higher OC concentrations were observed in bivalves from Kongsfjorden compared to the northern sampling locations Liefdefjorden and Sjuøyane. The spatial differences might be related to different water masses influencing Kongsfjorden (Atlantic) and the northern locations (Arctic), with differing phytoplankton bloom situations.


Disease-Induced Mortality Outweighs Hunting in Causing Wild Boar Population Crash After African Swine Fever Outbreak.
African swine fever (ASF) has been spreading in the Eurasian continent for more than 10 years now. Although the course of ASF in domestic pigs and its negative economic impact on the pork industry are well-known, we still lack a quantitative assessment of the impact of ASF on wild boar (Sus scrofa) populations under natural conditions. Wild boar is not only a reservoir for ASF; it is also one of the key wildlife species affecting structure and functioning of ecosystems. Therefore, knowledge on how ASF affects wild boar populations is crucial to better predict ecosystem response and for the design of scientific-based wild boar management to control ASF. We used a long-term camera trap survey (2012-2017) from the Białowieza Primeval Forest (BPF, Poland), where an ASF outbreak occurred in 2015, to investigate the impact of the disease on wild boar population dynamics under two contrasting management regimes (hunted vs. non-hunted). In the hunted part of BPF ("managed area"), hunting was drastically increased prior and after the first ASF case occurred (March 2015), whereas inside the National Park, hunting was not permitted ("unmanaged area," first detected case in June 2015). Using a random encounter model (REM), we showed that the density and abundance of wild boar dropped by 84 and 95% within 1 year following ASF outbreak in the unmanaged and managed area, respectively. In the managed area, we showed that 11-22% additional mortality could be attributed to hunting. Our study suggests that ASF-induced mortality, by far, outweighs hunting-induced mortality in causing wild boar population decline and shows that intensified hunting in newly ASF-infected areas does not achieve much greater reduction of population size than what is already caused by the ASF virus.


Tumor angiogenesis.
Angiogenesis requires the migration, differentiation and proliferation of endothelial cells. Tumor growth is angiogenesis-dependent and angiogenesis is directly or indirectly induced by the tumor. Induction of angiogenesis is, therefore, an important stage in carcinogenesis and in the development of metastasis. Numerous angiogenic factors have been identified, most of which are mitogenic for endothelial cells and only some of which are responsible for tube formation. Pharmacologic compounds such as heparin, heparin fragments and corticosteroids have been shown to be anti angiogenic substances. Recently two new inhibitors of angiogenesis, a cartilage-derived inhibitor and platelet factor 4 have been described.


Expression of functional toll-like receptors by B-chronic lymphocytic leukemia cells.
This study reports that B-chronic lymphocytic leukemia (B-CLL) cells display the same pattern of toll-like receptors (TLRs) proteins expression as normal B-cells, yet with overexpression of TLR9. Furthermore, TLR7 and TLR9 appear to be functional and liable to respond to specific ligands, respectively imidazoquinolines and CpG-ODN thus potentially opening new therapeutic approaches.


Induction of apoptosis in human hepatocellular carcinoma cells by extracts of Lannea coromandelica (Houtt.) Merr. and Diospyros castanea (Craib) Fletcher.
Herbal plants are a preferred source of anticancer agents. This study aims to screen the anticancer activity of a crude extract of twigs of (a) Bombax anceps Pierre var. anceps (BA); (b) Catunaregam tomentosa (Blume ex DC.) Tirveng. (CT); (c) Erythrophleum succirubrum Gagnep. (ES); (d) Lannea coromandelica (Houtt.) Merr. (LC); and (e) leaves and (f) twigs of Diospyros castanea (Craib) Fletcher (DC). The 50 % ethanol-water extracts were prepared from each plant sample. In vitro anticancer effects of six extracts on the human hepatocellular carcinoma cell line (HepG2) in terms of cytotoxicity were investigated by neutral red assay, apoptosis induction by 4',6-diamidino-2-phenylindole (DAPI) staining, and DNA fragmentation by agarose gel electrophoresis. Normal Vero cells were tested for comparison and to determine cancer selectivity. Gas chromatography-mass spectrometry analysis was performed to identify the compounds in the extracts. The six crude extracts had different cytotoxicities and were classified into three groups based on their IC50 value and selectivity index (SI). DC (twig) crude extract had both a high cytotoxicity and SI toward HepG2 cells comparable to melphalan (P = 0.023). The crude extracts of DC (leaves), LC (twig), and BA (twig) had moderate cytotoxicity and a lower SI. Although all crude plant extracts induced apoptosis in more than 50 % of the DAPI-positive apoptotic HepG2 cells, only DC (twig) and LC (twig) showed laddering in the DNA fragmentation assay. 2-Palmitoylglycerol was the major compound common to both. Pyrogallol and lupeol were the major compounds in DC (twig) crude extract. Hexadecanoic acid and octadecenoic acid were the major compounds in LC (twig) crude extract, which had high toxicity but low selectivity. Ethanolic extracts from DC and LC twigs induced apoptosis in the HepG2 cell line. Pyrogallol and lupeol in DC (twig) might be responsible for the cytotoxicity toward the HepG2 cancer cells.


Regulation of Microvascular Function by Adipose Tissue in Obesity and Type 2 Diabetes: Evidence of an Adipose-Vascular Loop.
In recent years, the general concept has emerged that chronic low-grade inflammation is the condition linking excessive development of adipose tissue and obesity-associated pathologies such as type 2 diabetes and cardiovascular diseases. Obesity and type 2 diabetes are characterized by a diminished production of protective factors such as adiponectin and increased detrimental adipocytokines such as leptin, resistin, interleukin-6 (IL-6), tumor necrosis factor-alpha (TNFα), and monocyte chemoattractant protein-1 (MCP-1) by adipose tissue. Moreover, the evidence that the growth of the fat mass is associated with an accumulation of adipose tissue macrophages and T-lymphocytes has raised the hypothesis that the development of an inflammatory process within the growing fat mass is a primary event involved in the genesis of systemic metabolic and vascular alterations. This crosstalk of adipocyte, macrophage, lymphocyte, endothelial cells, and vascular smooth muscle cells contribute to the production of various cytokines, chemokines, and hormone-like factors, which actively participate in the regulation of vascular function by an endocrine and/or paracrine pattern. Thus, the signaling from perivascular adipose to the blood vessels is emerging as a potential therapeutic target for obesity and diabetes-associated vascular dysfunction.


Numerical calculations of switched magnetic field gradients during magnetic resonance imaging.
During magnetic resonance imaging (MRI) pulse-sequences the human body is exposed to switched magnetic gradient fields. These gradients become stronger and are switched faster for fast imaging. Effects resulting from these fields with trapezoidal waveforms are on the one hand sensory perception of induced currents and on the other hand muscular and cardiac stimulation. All three components of the current density induced by gradient pulse sequence were analysed in a high-resolution model of the human torso. The evaluation of the calculated data was performed thoroughly in the region of the heart muscle of the torso model to find out how different waveforms of the switched gradient field influence strength and direction of induced currents.


[Changing trend of incidence and mortality of esophageal cancer during 2010-2016 in Henan Province, China].
Objective: To estimate the incidence and mortality of esophageal cancer in 2016 and their changing trend during 2010-2016 according to the cancer registration data in Henan province. Methods: The data quality including completeness, validity, and reliability of local registries which submitted the cancer registration data of 2016 were assessed according to the criteria of Guideline on Cancer Registration in China and IARC/IACR. Esophageal cancer cases (ICD10: C15) were extracted from the database, and the incidence and mortality stratified by gender, age, and areas (urban/rural) were calculated, the incidence and mortality of provincial cancer were estimated combined with provincial population data. China's 2000 census population and Segi's population were used to calculate the age-standardized rate. Joinpoint model was used to estimate the changing trend of age standardized incidence and mortality along with the calendar year. Results: Approximately 40.10 thousand new esophageal cancer cases were diagnosed in Henan in 2016, accounting for 13.46% of all new cancer cases, and it ranked the third among cancer of all sites. The crude incidence of esophageal cancer was 37.21/100 000 with an age-standardized incidence rate by China standard population (ASIRC) of 26.74/100 000 and an age-standardized incidence rate by world standard population (ASIRW) of 27.12/100 000. The incidence of esophageal cancer in males was higher than that in females, with the ASIRC of 34.53/100 000 and 19.19/100 000, respectively. It was higher in rural areas than that in urban areas, with the ASIRC of 28.13/100 000 and 20.90/100 000, respectively. About 29.30 thousand deaths of esophageal cancer in Henan in 2016, accounting for 15.61% of all cancer deaths in Henan, which ranked the third among cancer of all sites. The crude mortality rate was 27.14/100 000 with an age-standardized mortality rate by China standard population (ASMRC) of 18.74/100 000 and an age-standardized mortality rate by world standard population (ASMRW) of 18.78/100 000. The mortality in males was higher than that in females, with the ASMRC of 24.78/100 000 and 13.12/100 000, respectively. It was also higher in rural areas than that in urban areas, with the ASMRC of 19.48/100 000 and 15.73/100 000, respectively. The ASIRC and ASMRC were declining with annual percent change (APC) of 3.12% (APC=-3.12%; 95%CI: -5.30%, -0.90%; P=0.015) and 2.47% (APC=-2.47%; 95%CI: -4.70%, -0.20%; P=0.039) during 2010-2016. However, the significant declining trend was only observed in rural areas in Henan, and the changing trend was same between males and females. Conclusions: The incidence and mortality of esophageal cancer are declining since 2010, however, the disease burden remains large in Henan. Therefore, comprehensive prevention and control efforts should be strengthened according to its epidemic characteristics and risk factors.


Special Stains and Immunohistochemical Stains in Hair Pathology.
Patterns in scalp biopsies can overlap, and distinction may be difficult. To review the current knowledge about the usefulness of special stains and immunohistochemical stains (IHC) for the diagnosis of hair disorders. The authors used the search engines PubMED, MEDLINE, and MeSH to retrieve articles on the application of special stains and IHC in hair pathology. The authors selected 65 relevant articles discussing the use of special stains and IHC markers in scalp biopsies, including case reports and original articles. No reviews on the subject were found. Although fungal stains, such as periodic acid-Schiff, are very helpful in the diagnosis of noninflammatory tinea capitis, they may be negative in kerion. Elastic stains may help to diagnose end-stage scarring alopecia on vertical sections. Stains for mucin may help to distinguish lupus erythematosus from lichen planopilaris. Lymphocytic markers may assist in the diagnosis of lymphoma-associated alopecia. On a practical level, there is no evidence to recommend the routine use of a stain or a panel of stains in hair pathology. No stain can distinguish between nonscarring and early scarring alopecia. Most IHC stains are currently limited to the experimental and research setting.


Transition-metal-mediated synthesis of novel carbocyclic nucleoside analogues with antitumoral activity.
A diversity-oriented, enantioselective synthesis of new (monoprotected) carbocyclic nucleoside analogues (CNAs) with the nucleobase attached to a 3-hydroxymethyl-4-trialkylsilyloxymethylcyclopent-2-en-1-yl scaffold was developed. As a key intermediate, racemic (5SR,8RS)-8-allyloxy-2-trimethylsilyl-7-oxa-bicyclo[3.3.0]-oct-1-en-3-one was prepared from 1,1-diallyloxy-3-trimethylsilyl-2-propyne in a cobalt-mediated Pauson-Khand reaction. The enantiomerically pure material was obtained through efficient kinetic resolution (selectivity factor s >/= 40 at -78 degrees C) by means of an oxazaborolidine-catalyzed borane reduction (CBS reduction) with catecholborane. The absolute configuration of the resolved products was determined by CD spectroscopy, Mosher ester analysis, and chemical correlation. Subsequent steps involve diastereoselective ketone reduction and fully regio- and diastereoselective introduction of the nucleobase through Pd(0)-catalyzed allylic substitution. The generality of the method was demonstrated by preparation of CNAs in both enantiomeric series with all five natural nucleobases, as well as 5-bromouracil, 5-fluorouracil, and 6-chloropurine. Screening of the various compounds in a cytotoxicity assay with BJAB and ALL tumor cell lines revealed that some of the compounds possess pronounced antitumoral properties (LD50 values down to 9 microM, as determined by lactate dehydrogenase release after 48 h). By measuring DNA fragmentation, it could be shown that the activity results from induction of apoptosis.


An Important Need to Monitor from an Early Age the Neurotoxins in the Blood or by an Equivalent Biomarker.
An overwhelming amount of evidence now suggests that some people are becoming overloaded with neurotoxins. This is mainly from changes in their living environment and style, coupled with the fact that all people are different and display a broad distribution of genetic susceptibilities. It is important for individuals to know where they lie concerning their ability to either reject or retain toxins. Everyone is contaminated with a certain baseline of toxins that are alien to the body, namely aluminum, arsenic, lead, and mercury. Major societal changes have modified their intake, such as vaccines in enhanced inoculation procedures and the addition of sushi into diets, coupled with the ever-present lead, arsenic, and traces of manganese. It is now apparent that no single toxin is responsible for the current neurological epidemics, but rather a collaborative interaction with possible synergistic components. Selenium, although also a neurotoxin if in an excessive amount, is always present and is generally more present than other toxins. It performs as the body's natural chelator. However, it is possible that the formation rates of active selenium proteins may become overburdened by other toxins. Every person is different and it now appears imperative that the medical profession establish an individual's neurotoxicity baseline. Moreover, young women should certainly establish their baselines long before pregnancy in order to identify possible risk factors.


Home and health--on solid foundations?
This article is based on a WHO survey confirming that a large part of humanity lacks adequate shelter or knowledge of how to obtain the best possible health benefits from housing. The reasons for this state of affairs, and the health sector's role in overcoming it, are discussed.


Study of the destructive effect to inherent quality of Angelicae dahuricae radix (Baizhi) by sulfur-fumigated process using chromatographic fingerprinting analysis.
The after-harvesting sun-dried process of Angelicae dahuricae radix (Chinese name: Baizhi) was previously the traditional treatment for commodity. Over recent decades the natural drying process for some fleshy roots or rhizomes of Chinese materia medica has been replaced by sulfur-fumigation for curtailing the drying duration and pest control. We used high performance liquid chromatography (HPLC) and high performance thin-layer chromatography (HPTLC) fingerprinting analysis to investigate the potential damaging effect of the sulfur-fumigating process. The experimental conditions were as follows. HPTLC analysis was carried out on pre-coated silica-gel 60 plate, twice development was performed with two solvent systems (mobile phase) A, chloroform-ethyl acetate (10:1) and B, hexane-chloroform-ether (4:1:2); the fluorescent images were observed under UV 365 nm. HPLC was preceeded on Zorbax SB-C(18) column; the linear gradient elution was conducted with mobile phase prepared from methanol-0.5% acetic acid; column temperature was at 25 degrees C; the detection wavelength was 250 nm. We found serious degradation of the majority of coumarins in sulfur-fumigated Baizhi. The destructive effect was manifested by the defaced chromatographic profile and verified by imitating the sulfur dioxide reaction with the constituents in Baizhi in the laboratory. It is suggested that sulfur-fumigation process is an unacceptable approach for processing herbal drugs.


Spatial learning results in elevated agmatine levels in the rat brain.
Accumulating evidence suggests that agmatine, a metabolite of L-arginine by arginine decarboxylase, is a novel neurotransmitter, and exogenous agmatine can modulate behavior functions including learning and memory. However, direct evidence of its involvement in learning and memory processes is currently lacking. This study measured agmatine levels in the hippocampus, parahippocampal region, cerebellum, and vestibular nucleus in rats that were trained to find a hidden escape platform in the water-maze task, or forced to swim in the pool with no platform presented, or kept in the holding-box, using liquid chromatography/mass spectrometry. Compared with the swimming only group and holding-box group, agmatine levels were significantly increased in the CA1 and dentate gyrus subregions of the hippocampus, the entorhinal cortex and the vestibular nucleus in the water-maze training group. These results, for the first time, demonstrate spatial learning-induced region-specific elevation in agmatine, and raise a novel issue of the involvement of agmatine in the processes of learning and memory.


Manipulation of Subwavelength Periodic Structures Formation on 4H-SiC Surface with Three Temporally Delayed Femtosecond Laser Irradiations.
Controlling laser-induced periodic surface structures on semiconductor materials is of significant importance for micro/nanophotonics. We here demonstrate a new approach to form the unusual structures on 4H-SiC crystal surface under irradiation of three collinear temporally delayed femtosecond laser beams (800 nm wavelength, 50 fs duration, 1 kHz repetition), with orthogonal linear polarizations. Different types of surface structures, two-dimensional arrays of square islands (670 nm periodicity) and one-dimensional ripple structures (678 nm periodicity) are found to uniformly distribute over the laser-exposed areas, both of which are remarkably featured by the low spatial frequency. By altering the time delay among three laser beams, we can flexibly control the transition between the two surface structures. The experimental results are well explained by a physical model of the thermally correlated actions among three laser-material interaction processes. This investigation provides a simple, flexible, and controllable processing approach for the large-scale assembly of complex functional nanostructures on bulk semiconductor materials.


Pressure-equalizing earplugs do not prevent barotrauma on descent from 8000 ft cabin altitude.
The aim of this study was to evaluate the effect of pressure-equalizing earplugs available in major airports and drugstores. No previous study has focused on preventing barotrauma using these earplugs. Blinded and double-blinded, one type of pressure-equalizing earplugs (JetEars) was studied in 27 volunteers disposed to ear barotrauma. They acted as their own controls with an active earplug in one ear and a placebo earplug in the other ear at random. All were exposed to the same well-defined pressure profile for 1 h at 8000 ft, comparable to the environment in civil commercial air travel in a pressurized cabin. Satisfaction was assessed by questionnaire and objective results were evaluated prior to and after the pressure exposure by tympanometry and otoscopy using the Teed classification. The majority of the volunteers (78%) reported a pleasant noise-reducing feeling using the earplugs. However, 75% also experienced ear pain during descent. In comparing the middle ear pressure before and after pressurization, a decrease was found in ears with both active earplugs and placebo earplugs. No difference between the active and the placebo earplugs were found. Furthermore, after evaluation of the two groups of ears using otoscopy, no prevention of barotrauma was found. In fact, the ears using an active pressure-equalizing earplug scored significantly worse (p = 0.033). Feelings of noise reduction were reported, but no prevention of barotrauma could be demonstrated with the use of pressure-equalizing earplugs. Pressure-equalizing earplugs cannot be recommended in air travel for preventing ear barotrauma.


Forty-eight hours of unloading and 24 h of reloading lead to changes in global gene expression patterns related to ubiquitination and oxidative stress in humans.
Although short-term disuse does not result in measurable muscle atrophy, studies suggest that molecular changes associated with protein degradation may be initiated within days of the onset of a disuse stimulus. We examined the global gene expression patterns in sedentary men (n = 7, mean age ± SD = 22.1 ± 3.7 yr) following 48 h unloading (UL) via unilateral lower limb suspension and 24 h reloading (RL). Biopsy samples of the left vastus lateralis muscle were collected at baseline, 48 h UL, and 24 h RL. Expression changes were measured by microarray and gene clustering; identification of enriched functions and canonical pathways were performed using the Database for Annotation, Visualization and Integrated Discovery (DAVID) and Ingenuity Pathway Analysis (IPA). Four genes were validated with quantitative RT-PCR (qRT-PCR), and protein levels were measured with Western blot. Of the upregulated genes after UL, the most enriched functional group and highest ranked canonical pathway were related to protein ubiquitination. The oxidative stress response pathway was the second highest ranked canonical pathway. Of the downregulated genes, functions related to mitochondrial metabolism were the most highly enriched. In general, gene expression patterns following UL persisted following RL. qRT-PCR confirmed increases in mRNA for ubiquitin proteasome pathway-related E3 ligase Atrogin1 (but not accompanying increases in protein products) and stress response gene heme oxygenase-1 (HMOX, which showed a trend toward increases in protein products at 48 h UL) as well as extracellular matrix (ECM) component COL4A3. The gene expression patterns were not reversed on RL, suggesting that molecular responses to short-term periods of skeletal muscle inactivity may persist after activity resumes.


[Isolation, purification of collagen from soft-shelled turtle calipash for application in biomaterial].
Recently, research on collagen attracts more interests due to its good biological compatibility. The present study attempted to establish a fast and efficient method to purify collagen from soft-shelled turtle and to explore its application in biological materials. The structure and type of collagen fiber in calipash were determined by van Gieson staining and Picrosirius red staining, which could contribute to the isolation of collagen from soft-shelled turtle Calipash (STCC). Collagen fibers were in high content and the main collagen fiber was type I in STCC. The crude STCC solution was purified by dialysis with different cut-off molecular weight. SDS-PAGE demonstrated that the best purification was in applying 100 kDa dialysis bags after 48 h. The water absorbing capacity and holding capacity of STCC were up to 12.06 g/g and 98.21%, respectively. STCC can be degraded by collagenase in vitro entirely after 72 h. The hemolysis, skin sensitization, hemostatic and wound healing of STCC were determined by using SD rat model, and the collagen cross-linked by glutaric dialdehyde was set as a comparison. STCC and STCC cross-linked did not result in destructed red blood cell, inflamed and sensitized skin. Both materials exhibited good hemostatic effect. Thus, STCC improved the wound healing efficiently. This study implies a potential of STCC in the field of biomaterial.


Effects of Magnitude on the Displacement of Leisure Items by Edible Items During Preference Assessments.
Studies on preference assessments have shown that when both edible and leisure items are compared, edible items tend to displace leisure items in preference hierarchies. However, the mechanisms behind this process are currently unclear. One possibility is that displacement may be a product of the relatively brief periods of access to leisure items typically used in preference assessments. The purpose of the current investigation was to examine whether the duration of access to leisure items affects displacement. In this study, participants chose between preferred leisure items and the edible items that had previously been shown to displace those leisure items in a preference hierarchy. Duration of access to the leisure item was systematically increased across series to identify the magnitude at which leisure items became more preferred than edible items. Results indicate that as the duration of access to leisure items increases, displacement decreases.


The copper-catalyzed N-arylation of indoles.
A general method for the N-arylation of indoles using catalysts derived from CuI and trans-1,2-cyclohexanediamine (1a), trans-N,N'-dimethyl-1,2-cyclohexanediamine (2a), or N,N'-dimethyl-ethylenediamine (3) is reported. N-Arylindoles can be produced in high yield from the coupling of an aryl iodide or aryl bromide with a variety of indoles.


A Presynaptic Protein Is a Net Gain for Pancreatic Tumor Progression.
Cancer-associated fibroblasts conduct an aberrant wound-healing response, including mechanisms that restrain and others that support tumor progression. In this issue of Cancer Discovery, Francescone and colleagues demonstrate expression of presynaptic protein NetG1 on fibroblasts in pancreatic ductal adenocarcinoma and characterize tumor-supportive functions of NetG1 in this context, including metabolic and immune-modulatory mechanisms.See related article by Francescone et al., p. 446.


Comminuted articular fractures of the distal radius. Results of conservative treatment.
Fifty-nine comminuted articular fractures of the distal radius which had received conservative treatment were reviewed after an average of 3 1/2 years. The results--excellent in 15 patients, good in 30, fair in 12, and poor in 2--were closely linked to the quality of the articular reduction. In patients with a residual malalignment greater than 2 mm, a relatively high incidence of both degenerative arthritis (31%) and unsatisfactory results (56%) was found. The presence of a "die punch" fragment often precluded acceptable fracture reduction and was therefore responsible for many poor clinical and radiographic results. The quality of the extraarticular reduction proved to be of little importance to the final outcome.


Thrombotic microangiopathy as a complication of recurrent pancreatitis.
Acute pancreatitis as a cause of thrombotic microangiopathy is very rare. We report a case of 40-year-old woman with idiopathic recurrent pancreatitis, who presented with acute pancreatitis complicated by thrombotic microangiopathy. Although thrombotic thrombocytopenic purpura/hemolytic uremic syndrome (TTP/HUS) has been reported as causing acute pancreatitis, the induction of TTP/HUS by pancreatitis is rare. As far as we are aware this is the first reported case of TTP/HUS in association with pancreatitis in India. Our patient had a complete recovery of her thrombotic microangiopathy following plasma exchange therapy.


Elimination pathways of cyclosarin (GF) mediated by β-cyclodextrin in vitro: pharmacokinetic and toxicokinetic aspects.
Cyclodextrins (CD) are promising small molecular scavengers showing favourable degradation of extremely toxic organophosphorus compounds (OP) such as tabun (GA), soman (GD) or cyclosarin (GF). For β-CD derivatives as potential OP antidotes with low intrinsic toxicity it is of great interest to completely understand the modes of interaction of both compounds in terms of OP detoxification. The mechanisms of CD action are not completely understood which prompted us to investigate the interactions of GF and β-cyclodextrin (β-CD) as model compounds. Using positive electrospray ionization mass spectrometry (ESI/MS), the formation of covalent conjugates of β-CD with O-cyclohexylmethylphosphonate (CHMP) residue was detected for the first time and was examined in vitro. With a newly developed LC-MS method the formation of O-cyclohexylmethylphosphonic acid (CHMPA) (i.e. GF hydrolysis) and covalent CHMP-β-CD conjugates was analyzed. Compared to water, tris(hydroxymethyl)aminomethane (TRIS) reduced the formation of covalent conjugates but amplified formation of CHMPA. Depending on experimental conditions the degradation of GF by β-CD may be preferably catalytic or stoichiometric. For illustrating different possible reaction pathways a scheme was established that could support the idea of β-CD acting as an artificial enzyme. These results provide an important insight into the β-CD mediated detoxification pathways of GF.


Temporospatial characteristics of gait in patients with lower limb muscle hypertonia after traumatic brain injury.
To characterize gait characteristics of adults with traumatic brain injury (TBI) and lower limb muscle hypertonia, distinguishing gait adaptations inherent to TBI motor impairment from those of healthy subjects walking at slower speed. Temporospatial and kinematic data of 31 patients with TBI (41 ± 30 months post-injury) walking at self-selected speed (free speed) were compared with 31 healthy subjects walking at free and very slow speeds using an optoelectronic motion analysis system. All step parameters differed (p < 0.05) between more affected (MA) and less affected (LA) sides in TBI except foot angle and toe clearance. Significant differences existed between TBI and controls in most parameters regardless of speed. These differences frequently involved the LA side. In TBI, most temporospatial parameters significantly correlated with stride velocity, whereas the averaged lower limb Ashworth score on the MA side (2.1 ± 0.4) showed few significant correlations. Gait deviations in subjects with TBI and lower limb muscle hypertonia cannot be solely explained by slower walking. The preponderance of changes involving the LA side particularly suggests prevalent use of compensatory walking strategies. Temporospatial gait parameters are not closely related to static measures of muscle hypertonia after TBI.


Respect for the journey: a survivor-led investigation of undergoing psychotherapy assessment.
Psychotherapy assessments are key decision points for both clients and services, carrying considerable weight on both sides. Limited research indicates that assessments have immediate and long-term impacts on clients, particularly where trauma has been experienced, affecting engagement with therapy. Understanding assessments from clients' perspectives can inform service development and improve client experience. This is a survivor-led exploration of clients' experiences of undergoing assessment for talking therapies. Interviews were conducted with seven people who had undergone assessment for psychological therapies in third sector and NHS services. Interviews were recorded, transcribed and analysed thematically. The core theme was 'respect for the journey' reflecting the need expressed by participants for their life experiences prior to the assessment to be given full respect and consideration. Six sub-themes were identified: trauma and desperation, fear of judgement, search for trust and safety, sharing and withholding (a balancing act), feeling deconstructed, and finding hope. The findings highlight the heightened emotional power surrounding psychotherapy assessments, reflecting the journey participants had undertaken to reach this point. The dilemma facing clients at the heart of an assessment-how much to share and how much to withhold-demonstrates the importance for services and assessors of treating the journey a client has made to the assessment with care and respect. Findings indicate the value of services and practitioners undertaking a trauma-informed approach to assessment encounters.


Hidradenitis suppurativa in patients with Down syndrome.
Literature data about hidradenitis suppurativa (HS) in patients with Down syndrome (DS) are limited. In this retrospective study, 6 (4M/2F; mean age: 18.7 years) out of 313 patients affected by HS (1.9%) had DS. The age of appearance of HS was from 9 to 14 years. No family history of HS was present. BMI ranged from 20.1 to 29.9. In all patients, HS was located below the diaphragm. Five out of six patients were staged as Hurley II severity.


Substance use during pregnancy: impact on Colorado community hospital.
Neonatal Abstinence Syndrome (NAS) leads to increased length of stay (LOS), which leads to increased healthcare costs, and can cause financial burdens for hospitals. The purpose of the study was to determine the impact of substance use by pregnant women on a Colorado (CO) community hospital after state legalization of recreational cannabis. Data were gathered retrospectively through the electronic health record at an inpatient facility and described 607 mothers and 419 newborns (total N = 1026) who tested positive for drugs (urinalysis or blood for mother and urine, meconium, or cord blood for newborns). Screening for drugs was at discretion of healthcare provider if mother reported use or newborn showed symptoms of NAS. The patients who were not screened or tested negative were excluded from consideration. Newborns exposed to cannabis were compared to those exposed to other drugs (opioids, methadone, cocaine, barbiturates, benzodiazepines, amphetamines) on costs of newborn hospitalization, based on type of newborn bed and length of stay (LOS). Group comparisons were done using Cochran-Armitage chi-square tests and two-sample t-tests. The proportion of screened patients testing positive for illicit and prescribed substances increased significantly from 2013 (33.4%) to 2017 (50.2%) (p < 0.001). The LOS of drug-exposed newborns increased significantly over the years (p < 0.0001). Newborns testing positive for cannabis were more likely to remain in a normal newborn nursery (NSY) bed (69.8%) than those testing positive for other drugs (27.7%), with an average hospital LOS (4.6 days) significantly shorter (p < 0.001) than that of other-drug exposed newborns (14.2 days). Combined healthcare costs for other-drug exposed newborns ($23,495,221) were significantly higher (p < 0.001) than for cannabis-exposed newborns ($2,885,139); both groups had significantly higher costs (p < 0.001) than normal healthy newborns ($2,166,649). Drug-exposed newborns have a significant financial impact on hospital healthcare costs, largely due to more expensive bed placement and longer LOS.


Glycolate metabolism in algal chloroplasts: inhibition by salicylhydroxamic acid (SHAM).
Unicellular green algae such as Chlamydomonas and Dunaliella excrete small amounts of glycolate during active photosynthesis. This phenomenon has been explained by the fact that these algae do not have leaf-type peroxisomes and glycolate oxidase; instead, they have a limited capacity to metabolise glycolate in their mitochondria by a membrane-associated glycolate dehydrogenase. Salicylhydroxamic acid (SHAM), an inhibitor of alternative oxidase in plant and algal mitochondria, stimulates glycolate excretion by the algae or their isolated chloroplasts 5-fold. In the presence of SHAM, cells of Chlamydomonas or Dunaliella grown with high-CO2 (5% CO2 in air, v/v) or adapted with air levels of CO2 excreted glycolate at a rate of about 14 micro mol glycolate mg-1 Chl h-1. Aminooxyacetate (AOA), an inhibitor of aminotransferases, also increases glycolate excretion by the algal cells or chloroplasts but at a lower rate (about 50%) than SHAM. The algal, light dependent, SHAM-sensitive glycolate oxidizing system in the chloroplasts appears to be the primary site for glycolate oxidation, and it is different and more active then the minor mitochondrial glycolate dehydrogenase.


Histologic correlates of progression-free interval and survival in ovarian clear cell adenocarcinoma.
Unlike other ovarian epithelial cancers, histologic measures of differentiation of ovarian clear cell adenocarcinoma have not been found to be reliable predictors of progression-free interval and survival. Forty-two consecutively treated patients with pure ovarian clear cell adenocarcinoma were identified and all histologic materials were reviewed. The following histologic features were assessed: architectural pattern (tubular/tubulocystic, papillary, solid, and mixed), average and maximal mitotic activity per 10 high-power fields (hpf's), percentage of cells with clear cytoplasm, and nuclear grading (both Fuhrman et al.'s (Am. J. Surg. Pathol. 6, 655-663, 1982) and Christopherson et al.'s (Cancer 49, 1511-1523, 1982) methods). Surgical stage was most predictive of survival (P < 0.01) and subsequent comparisons using Cox proportional hazards modeling were adjusted for Stages III and IV. Greater than six mitotic figures per 10 hpf's predicted a poorer survival (P = 0.05) but was not predictive of progression-free interval (P = 0.28). Survival and progression-free interval in patients with tumors of mixed architectural pattern tended to be shorter than those for patients where one type did predominate, but this was not statistically significant (P = 0.06). The tubulocystic pattern was not predictive of patient outcome nor was either method of nuclear grading. Stage and average mitotic activity seem to be the best predictors of survival for patients with ovarian clear cell adnocarcinoma, while architectural pattern and nuclear grading are not as reliable.


Interpenetrating Networks of Collagen and Hyaluronic Acid That Serve as In Vitro Tissue Models for Assessing Macromolecular Transport.
High-fidelity preclinical in vitro tissue models can reduce the failure rate of drugs entering clinical trials. Collagen and hyaluronic acid (HA) are major components of the extracellular matrix of many native tissues and affect therapeutic macromolecule diffusion and recovery through tissues. Although collagen and HA are commonly used in tissue engineering, the physical and mechanical properties of these materials are variable and depend highly on processing conditions. In this study, HA was chemically modified and crosslinked via hydrazone bonds to form interpenetrating networks of crosslinked HA (HAX) with collagen (Col). These networks enabled a wide range of mechanical properties, including stiffness and swellability, and microstructures, such as pore morphology and size, that can better recapitulate diverse tissues. We utilized these interpenetrating ColHAX hydrogels as in vitro tissue models to examine macromolecular transport and recovery for early-stage drug screening. Hydrogel formulations with varying collagen and HAX concentrations imparted different gel properties based on the ratio of collagen to HAX. These gels were stable and swelled up to 170% of their original mass, and the storage moduli of the ColHAX gels increased over an order of magnitude by increasing collagen and HA concentration. Interestingly, when HAX concentration was constant and collagen concentration increased, both the pore size and spatial colocalization of collagen and HA increased. HA in the system dominated the ζ-potentials of the gels. The hydrogel and macromolecule properties impacted the mass transport and recovery of lysozyme, β-lactoglobulin, and bovine serum albumin (BSA) from the ColHAX gels─large molecules were largely impacted by mesh size, whereas small molecules were influenced primarily by electrostatic forces. Overall, the tunable properties demonstrated by the ColHAX hydrogels can be used to mimic different tissues for early-stage assays to understand drug transport and its relationship to matrix properties.


Mutual control of intracellular localisation of the patterning proteins AtMYC1, GL1 and TRY/CPC in Arabidopsis.
Trichome and root hair patterning is governed by a gene regulatory network involving TTG1 and several homologous MYB and bHLH proteins. The bHLH proteins GL3 and EGL3 are core components that serve as a regulatory platform for the activation of downstream genes. In this study we show that a homologue of GL3 and EGL3, AtMYC1, can regulate the intracellular localisation of GL1 and TRY. AtMYC1 protein is predominantly localised in the cytoplasm and can relocate GL1 from the nucleus into the cytoplasm. Conversely, AtMYC1 can be recruited into the nucleus by TRY and CPC, concomitant with a strong accumulation of TRY and CPC in the nucleus. When AtMYC1 is targeted to the nucleus or cytoplasm by nuclear localisation or export signals (NLS or NES), respectively, the intracellular localisation of GL1 and TRY also changes accordingly. The biological significance of this intracellular localisation is suggested by the finding that the efficiency of rescue of trichome number is significantly altered in NES and NLS fusions as compared with wild-type AtMYC1. Genetic analysis of mutants and overexpression lines supports the hypothesis that AtMYC1 represses the activity of TRY and CPC.


Conjugated human hemoglobin as a physiological oxygen carrier--pyridoxalated hemoglobin polyoxyethylene conjugate (PHP).
Problems associated with specific physiological properties of Hb-based blood substitutes, such as low P50, short plasma half-life and nephrotoxicity are still major issues to be addressed. Extensive investigations aimed at overcoming these problems have resulted in the preparation of pyridoxalated-hemoglobin-polyoxyethylene conjugate (PHP). PHP was developed from human hemoglobin by two major chemical modifications; pyridoxylation for the purpose of lowering the oxygen affinity (P50 of 19.5 +/- 1.2 mmHg), and coupling with polyoxyethylene (POE) to increase its molecular weight (to approximately 90 kdaltons). The circulating half-life of PHP is about 40 hours in dogs. Toxicological and physiological studies including renal function assessments have demonstrated that PHP does not have untoward effects on major organ functions. Its efficacy in transporting oxygen has been shown in ET and intracoronary perfusion, and in in vitro studies with sickle cells. Studies to date suggest that PHP is a promising candidate as a physiological oxygen carrier. In this paper the properties of PHP, its safety and efficacy aspects, and its potential as a clinical oxygen carrier are reviewed based on studies conducted in the Author's laboratory.