High-performance liquid chromatography-atmospheric pressure photoionization/tandem mass spectrometry for the detection of 17alpha-ethinylestradiol in hepatocytes.
Atmospheric pressure photoionization (APPI) as an interface for the high-performance liquid chromatography (HPLC)-tandem mass spectrometry (MS/MS) system was employed for the direct determination of 17alpha-ethinylestradiol (EE(2)) in the incubation mixtures to support in vitro hepatic clearance studies. For the APPI source, the radical cation of the analyte via charge exchange with the dopant radical cation was used for the detection of EE(2) in the positive ion mode. It was demonstrated that the major signals of EE(2) in the acetonitrile/water mobile phase were substantially increased by replacing toluene with anisole as the dopant. The effects of several experimental conditions on the photoionization efficiency of EE(2) in the dopant-assisted APPI source were explored. Electrospray ionization (ESI) source was also suitable for the analysis of the analyte; however, ESI required a derivatization step prior to analysis. The applicability of the proposed HPLC-APPI-MS/MS approach following a protein precipitation procedure for the determination of EE(2) at low nano-mole levels was examined with respect to assay specificity and linearity. The assay results obtained by both HPLC-APPI-MS/MS and HPLC-ESI-MS/MS methods were in good agreement.


[A Young Asylum Seeker with Hemoptysis and Positive Tuberculosis Screening: Not Always Tuberculosis!]
This paper reports on the case of a 19 year old asylum seeker from Eritrea who presented with hemoptysis, a positive tuberculosis screening (Enzyme Linked Immuno Spot Assay - EliSpot) and mushy faeces submitted with a suspected diagnosis of tuberculosis. Laboratory testing revealed thrombopenia, leukopenia and eosinophilia, while the chest X-ray was inconspicuous. Acid-proof rod bacteria were neither evident in bronchoscopy samples nor in expectorated sputum samples. However, sonographic findings showed a profound splenomegaly, and laboratory testing revealed a Schistosoma mansoni infection. This case demonstrates that in asylum seekers with suspected tuberculosis endemic diseases of the home country need to be considered as alternative diagnoses.


Virtual electrodes around anatomical structures and their roles in defibrillation.
Virtual electrodes from structural/conductivity heterogeneities are known to elicit wavefront propagation, upon field-stimulation, and are thought to be important for defibrillation. In this work we investigate how the constitutive and geometrical parameters associated with such anatomical heterogeneities, represented by endo/epicardial surfaces and intramural surfaces in the form of blood-vessels, affect the virtual electrode patterns produced. The steady-state bidomain model is used to obtain, using analytical and numerical methods, the virtual electrode patterns created around idealized endocardial trabeculations and blood-vessels. The virtual electrode pattern around blood-vessels is shown to be composed of two dominant effects; current traversing the vessel surface and conductivity heterogeneity from the fibre-architecture. The relative magnitudes of these two effects explain the swapping of the virtual electrode polarity observed, as a function of the vessel radius, and aid in the understanding of the virtual electrode patterns predicted by numerical bidomain modelling. The relatively high conductivity of blood, compared to myocardium, is shown to cause stronger depolarizations in the endocardial trabeculae grooves than the protrusions. The results provide additional quantitative understanding of the virtual electrodes produced by small-scale ventricular anatomy, and highlight the importance of faithfully representing the physiology and the physics in the context of computational modelling of field stimulation.


Orexin A induces GnRH gene expression and secretion from GT1-7 hypothalamic GnRH neurons.
Orexin A, a recently discovered hypothalamic peptide, has been shown to have a stimulatory effect on release of gonadotropin-releasing hormone (GnRH) from rat hypothalamic explants in vitro. However, it is presently unclear whether in vivo this effect is mediated directly at the level of the GnRH neuron, or via multiple afferent neuronal connections. Therefore, in the present study, we investigated the direct action of orexin A on GnRH neurons using the immortalized GnRH-secreting GT1-7 hypothalamic cells. Orexin-1 receptor (OX1R) expression was detected in GT1-7 cells by RT-PCR and Western blot. Results showed that 0.1-1 nM orexin A, when administered in culture media for 4 h, can significantly stimulate GnRH mRNA expression in GT1-7 cells (p < 0.05). Administration of 1 microM OX1R antagonist, SB-334867, completely blocked the observed orexin A responses in these cells, indicating that orexin A stimulation of GnRH neurons is specifically through OX1R. Moreover, 0.1 nM orexin A stimulated GnRH release after 30-45 min. To examine possible signal transduction pathways involved in mediating these effects, a MEK inhibitor (UO-126), PKC inhibitor (calphostin C), and PKA inhibitor (H-89), were used, with each blocking orexin A-induced GnRH transcription and release from immortalized cells. Collectively, our results show that orexin A is capable of directly stimulating GnRH transcription and neuropeptide release from these immortalized hypothalamic neurons, and that the effects of orexin A appear to be mediated via the OX1R, coupled with activation of the PKC-, MAPK- and PKA-signaling pathways. It is suggested that the stimulatory effect of orexin A on GnRH transcription and release may also occur directly at the level of GnRH neurons in vivo.


Echocardiographically Derived Pulse Wave Velocity and Diastolic Dysfunction Are Associated with an Increased Incidence of Atrial Fibrillation in Patients with Systolic Heart Failure.
Chronic heart failure (CHF) is an established risk factor of atrial fibrillation (AF), but the prognostic value of cardiac and hemodynamic parameters in assessing the risk of developing AF among patients with CHF is less defined. We followed an outpatients cohort of CHF patients secondary to left ventricular (LV) systolic dysfunction, who were free of AF at baseline. All patients underwent clinical evaluation, comprehensive echocardiography, and blood drawing in the same morning. Aortic pulse wave velocity (aPWV), a measure of aortic stiffness, was determined by Doppler echocardiography. A total of 77 patients (age 63 ± 9 years; 79% male) with mean LVEF (34 ± 8%) formed the study population. Fifteen patients developed incidental AF. At baseline, CHF patients who developed AF during follow-up had higher E-wave velocity (75 ± 2 cm/sec vs. 60 ± 2 cm/sec; P = 0.02), higher difference duration between mitral and pulmonary vein A velocity (A'-A), (10 ± 35 msec vs. 43 ± 44 msec P = 0.02), aPWV (7.1 ± 2.6 vs. 5.3 ± 1.9 m/sec P = 0.004), and furosemide dosage (110 ± 145 mg vs. 49 ± 48 mg P = 0.01) than those remaining free from AF. The two groups of patients did not significantly differ in terms of NYHA, LV volumes, ejection fraction, left atrial volume, creatinine, hemoglobin, renin, epinephrine, amino-terminal propeptide of type III and I procollagens, ACE inhibitor, and β-blocker dose (P > 0.1 for all). Notably, higher aPWV (P = 0.01) and longer A-A' duration (P = 0.04) were associated with an increased incidence of AF, independently of potential confounders. Increased aortic stiffness and LV diastolic dysfunction are strong predictors of new onset of AF among patients with systolic CHF.


Relationship between trauma narratives and trauma pathology.
In this study we examined the relationship between posttrauma pathology and the level of articulation (complexity) in rape narratives recounted by victims shortly after the assault. Degree of articulation was operationalized as the reading level of the narrative as determined by a computer program. Shortly after the trauma, reading level was correlated with severity of anxiety but not with posttraumatic stress disorder (PTSD) symptoms. Degree of the narrative articulation shortly after the trauma, however, was related to severity of later PTSD. These results are consistent with the hypothesis that the less developed trauma narratives hinder recovery from trauma.


Gamma-ray CT from incomplete projections for two-phase pipe flow.
A low-energy low-dose γ-ray computed tomography (CT) system used in the gas-liquid two-phase pipe flow measurement has been studied at Tianjin University in recent years. The γ-ray CT system, having a third-generation X-ray CT scanning configuration, is comprised of one 300mCi 241Am source and 17 CdZnTe detector units and achieves a spatial image resolution of about 7 mm. It is primarily intended to measure the two-phase pipe flow and provide improvement suggestions for industrial CT system. Recently we improve the design for image reconstruction from incomplete projection to optimize the scanning parameters and reduce the radiation dose. First, tomographic problem from incomplete projections is briefly described. Next, a system structure and a hardware circuit design are listed and explained, especially on time parameter setting of the pulse shaper. And then a detailed system analysis is provided in Section II, mainly focusing on spatial resolution, temporal resolution, system noise, and imaging algorithm. Finally, we carry on necessary static and dynamic experiments in a full scan (360°) and two sets of partial scan reconstruction tests to determine the feasibility of this γ-ray CT system for reconstructing the images from insufficient projections. And based on an A-variable algebraic reconstruction technique method, a specially designed algorithm, we evaluate the system performance and noise level of this CT system working quantitatively and qualitatively. Results of dynamic test indicate that the acceptable results can be acquired using a multi-source γ-ray CT system with the same parameters when the flow rate is less than 0.04 m/s and the imaging speed is slower than 33 frames/s.


Valproate and delta-sleep peptide display high efficacy against metaphit-induced audiogenic seizure in rats.
The effects of valproate (VPA) and delta sleep-inducing peptide (DSIP) on metaphit-induced generalized, audiogenic seizure in adult rat males were compared. The animals were i.p. injected with: (1) Saline; (2) metaphit (mp, 10 mg kg(-1)); 3. metaphit (10 mg kg(-1)) and 8 h later with DSIP (0.1, 0.2, 0.4 or 1.0 mg kg(-1)), 4. metaphit (10 mg kg(-1)) and 8 h later with VPA (50, 75 or 100 mg kg(-1)); 5. DSIP alone (1.0 mg kg(-1)) and 6. VPA, alone (100 mg kg(-1)). The rats were exposed to sound stimulation at hourly intervals and the behavior and EEG were analyzed. The EEG signals in metaphit rats appeared as a sleep-like pattern and spike-wave complexes with increased power spectra. Valproate and DSIP reduced the incidence of seizure and prolonged duration of latency in a dose-dependent manner. ED50 of valproate in the 1st hour after administration was 63.19 mg kg(-1) and that of DSIP 3.19 mg kg(-1) four hours after injection. This suggests that VPA, reached a peak of action immediately after the application, while DSIP had a prolonged action, mildly reducing, but not abolishing metaphit seizure. None of the applied VPA and DSIP doses eliminated the metaphit-provoked EEG signs of epileptiform activity.


The intraprostatic spiral. New treatment for urinary retention.
In a series of 45 consecutive patients with acute or chronic urinary retention, 41 were treated by insertion of an intraprostatic spiral using ultrasonic guidance under local anaesthesia. Insertion was successful in 35 patients and in 6 the spiral was inserted endoscopically. During a follow-up period of 12 months 8 patients died, all with a functioning spiral. The device was removed in 16 patients; in 6 cases the reasons for removal were related to the spiral and in 10 they were not. The spiral remained in situ in 17 patients and all had satisfactory voiding. This device is a good alternative to an indwelling catheter in patients awaiting prostatic surgery and also in those who are either unfit or unwilling to undergo prostatectomy.


Low-Latency Rendering With Dataflow Architectures.
Recent years have seen a resurgence of virtual reality (VR), sparked by the repurposing of low-cost COTS components. VR aims to generate stimuli that appear to come from a source other than the interface through which they are delivered. The synthetic stimuli replace real-world stimuli, and transport the user to another, perhaps imaginary, "place." To do this, we must overcome many challenges, often related to matching the synthetic stimuli to the expectations and behavior of the real world. One way in which the stimuli can fail is its latency-- the time between a user's action and the computer's response. We constructed a novel VR renderer, that optimized latency above all else. Our prototype allowed us to explore how latency affects human-computer interaction. We had to completely reconsider the interaction between time, space, and synchronization on displays and in the traditional graphics pipeline. Using a specialized architecture--dataflow computing--we combined consumer, industrial, and prototype components to create an integrated 1:1 room-scale VR system with a latency of under 3 ms. While this was prototype hardware, the considerations in achieving this performance inform the design of future VR pipelines, and our human factors studies have provided new and sometimes surprising contributions to the body of knowledge on latency in HCI.


The use of gauze: will it ever change?
Although the benefits of healing in a moist environment have been published worldwide, the use of woven gauze as a wound contact material still prevails in many countries. This article traces the history of gauze and problems associated with usage against the introduction of one of the first modern materials, the hydrocolloid. Why this revolution in dressing material did not herald an immediate change of practice away from gauze is examined. Since the 1970s, the range, availability and sophistication of these and other moisture-retentive dressings have increased dramatically, and yet it seems that some practitioners remain unconvinced. The processes that underpin personal and organisational change that may contribute to this reluctance are also considered.


Effects of neurofeedback training combined with transcranial direct current stimulation on motor imagery: A randomized controlled trial.
Neurofeedback (NFB) training and transcranial direct current stimulation (tDCS) have been shown to individually improve motor imagery (MI) abilities. However, the effect of combining both of them with MI has not been verified. Therefore, the aim of this study was to examine the effect of applying tDCS directly before MI with NFB. Participants were divided into an NFB group (n = 10) that performed MI with NFB and an NFB + tDCS group (n = 10) that received tDCS for 10 min before MI with NFB. Both groups performed 60 MI trials with NFB. The MI task was performed 20 times without NFB before and after training, and μ-event-related desynchronization (ERD) and vividness MI were evaluated. μ-ERD increased significantly in the NFB + tDCS group compared to the NFB group. MI vividness significantly increased before and after training. Transcranial direct current stimulation and NFB modulate different processes with respect to MI ability improvement; hence, their combination might further improve MI performance. The results of this study indicate that the combination of NFB and tDCS for MI is more effective in improving MI abilities than applying them individually.


A high-speed network for cardiac image review.
A high-speed fiber-based network for the transmission and display of digitized full-motion cardiac images has been developed. Based on Asynchronous Transfer Mode (ATM), the network is scaleable, meaning that the same software and hardware is used for a small local area network or for a large multi-institutional network. The system can handle uncompressed digital angiographic images, considered to be at the "high-end" of the bandwidth requirements. Along with the networking, a general-purpose multi-modality review station has been implemented without specialized hardware. This station can store a full injection sequence in "loop RAM" in a 512 x 512 format, then interpolate to 1024 x 1024 while displaying at 30 frames per second. The network and review stations connect to a central file server that uses a virtual file system to make a large high-speed RAID storage disk and associated off-line storage tapes and cartridges all appear as a single large file system to the software. In addition to supporting archival storage and review, the system can also digitize live video using high-speed Direct Memory Access (DMA) from the frame grabber to present uncompressed data to the network. Fully functional prototypes have provided the proof of concept, with full deployment in the institution planned as the next stage.


Health Care Costs Associated With Hospice Use For People With Dementia In The US.
Policy makers in the US are increasingly concerned that greater use of the Medicare hospice benefit by people with dementia is driving up costs. Yet this perspective fails to incorporate potential cost savings associated with hospice. We estimated the association between hospice use by people with dementia and health care costs, using Medicare Current Beneficiary Survey data from the period 2002-19. For community-dwelling people with dementia, Medicare costs were lower for those who used hospice than for those who did not, whether hospice enrollment was in the last three days ($2,200) or last three months ($7,200) of life, primarily through lower inpatient care costs in the last days of life. In nursing homes, total and Medicare costs were lower for hospice users with dementia who enrolled within a month of death than for those who did not use hospice. Total costs for the entire last year of life for those who used any days of hospice in the last year compared with no hospice did not differ, although Medicare costs were higher and Medicaid costs lower for those in nursing homes. Medicare policies that reduce hospice access and incentivize hospice disenrollment may actually increase Medicare costs, given that hospice cost savings generally derive from a person's last days or weeks of life.


Hsc70 rescues the synaptic vesicle trafficking defects caused by α-synuclein dimers.
Aberrant buildup of α-synuclein is associated with Parkinson's disease (PD) and other neurodegenerative disorders. At synapses, α-synuclein accumulation leads to severe synaptic vesicle trafficking defects. We previously demonstrated that different molecular species of α-synuclein produce distinct effects on synaptic vesicle recycling, and that the synaptic phenotypes caused by monomeric α-synuclein were ameliorated by Hsc70. Here, we tested whether Hsc70 could also correct synaptic deficits induced by α-synuclein dimers. Indeed, co-injection of Hsc70 with α-synuclein dimers completely reversed the synaptic deficits, resulting in synapses with normal appearance. This work lends additional support for pursuing chaperone-based strategies to treat PD and other synucleinopathies.


Stereocontrolled synthesis of psi[CH(CF3)NH]gly-peptides.
[reaction: see text] A novel class of peptidomimetics having a stereogenic [CH(CF(3))NH] replacement for a [CONH] peptide bond has been synthesized. The new compounds have been obtained in a stereocontrolled fashion using a kinetically controlled aza-Michael addition of chiral alpha-amino acid esters to trans-3,3,3-trifluoro-1-nitropropene. The stereoselectivity is strongly influenced by the solvent, the base, its stoichiometry, and the R side-chain. Diastereomeric ratios higher than 11:1 were achieved using H-Val-OtBu.HCl in toluene with 1.1 equiv of DIPEA.


[Promotion of hematogenous metastasis in relation to endothelial cell injury by treatment with anticancer drugs].
It has been reported that anticancer drugs at high concentration increase experimental hematogenous metastasis owing to endothelial injury. In this study, we evaluate the effects of anticancer drugs at clinical doses on endothelial cells in the process of metastasis. To do so, we have developed in vitro assay methods which can assess endothelial cell retraction and barrier function against invasion by tumor cells. 5-FU at clinical doses caused neither retraction nor decreasing barrier function, however, ADR and MMC caused retraction of endothelial cells and increased invasion by tumor cells. These effects reached maximum 12 hours after treatment with ADR or MMC, and the number of liver metastases was also significantly increased in in vivo study when tumor cells were injected via portal vein at 12 hours after administration of ADR. It was suggested that some kinds of anticancer drugs at the clinical dose may increase hematogenous metastasis in treatments.


Tumour necrosis factor-alpha is required for accumulation of dendritic cells in draining lymph nodes and for optimal contact sensitization.
Following skin sensitization epidermal Langerhans' cells (LC), many of which bear antigen, are stimulated to migrate from the skin and traffic via afferent lymphatics to lymph nodes draining the site of exposure. It has been proposed previously that tumour necrosis factor-alpha (TNF-alpha), a keratinocyte-derived epidermal cytokine (the expression of which is augmented following cutaneous sensitization), provides one signal for LC migration. In the experiments described here the influence of systemically administered neutralizing anti-TNF-alpha antibody on dendritic cell (DC) accumulation in draining lymph nodes has been investigated. Treatment with anti-TNF-alpha inhibited markedly the frequency of DC in draining nodes measured 18 hr following exposure to the skin allergens oxazolone and fluorescein isothiocyanate or to the non-sensitizing skin irritant sodium lauryl sulphate. Similar treatment with anti-TNF-alpha 2 hr prior to primary exposure to oxazolone impaired significantly the efficiency of skin sensitization measured 5 days later as a function of challenge-induced increases in ear thickness. The same antibody administered 18 hr following initial exposure to oxazolone was without effect on skin sensitization. These data confirm the importance of TNF-alpha for the migration of LC from the skin to draining lymph nodes and demonstrate that this cytokine is required for optimal contact sensitization.


Molecular epidemiology of white spot syndrome virus within Vietnam.
White spot syndrome virus (WSSV), the sole member of the virus family Nimaviridae, is a large double-stranded DNA virus that infects shrimp and other crustaceans. By alignment of three completely sequenced isolates originating from Taiwan (WSSV-TW), China (WSSV-CN) and Thailand (WSSV-TH), the variable loci in the genome were mapped. The variation suggests the spread of WSSV from a common ancestor originating from either side of the Taiwan Strait to Thailand, but support for this hypothesis through analysis of geographical intermediates is sought. RFLP analysis of eight Vietnamese WSSV isolates, of which six were collected along the central coast (VN-central) and two along the south coast (VN-south), showed apparent sequence variation in the variable loci identified previously. These loci were characterized in detail by PCR amplification, cloning and sequencing. Relative to WSSV-TW, all VN-central isolates showed a approximately 8.5 kb deletion in the major variable region ORF23/24, whereas the VN-south isolates contain a deletion of approximately 11.5 or approximately 12.2 kb, compared to a approximately 1.2 or approximately 13.2 kb deletion in WSSV-CN and WSSV-TH, respectively. The minor variable region ORF14/15 showed deletions of various sizes compared with WSSV-TH for all eight VN isolates. The data suggest that the VN isolates and WSSV-TH have a common lineage, which branched off from WSSV-TW and WSSV-CN early on, and that WSSV entered Vietnam by multiple introductions. A model is presented for the spread of WSSV from either side of the Taiwan Strait into Vietnam based on the gradually increasing deletions of both 'variable regions'. The number and order of repeat units within ORF75 and ORF125 appeared to be suitable markers to study regional spread of WSSV.


Role of laminin in the morphogenetic cascade during coculture of Sertoli cells with peritubular cells.
Observations summarized in this article demonstrate an essential role of laminin during the restructuring processes that occur during coculture of Sertoli cells with testicular peritubular cells. The data presented indicate that laminin becomes detectable on the free surfaces of Sertoli cells only after reaggregation of Sertoli cells begins, coincident with the initiation of repolarization at a specific stage of the morphogenetic cascade. We infer that laminin deposited at this time serves as a cohesion molecule that permits peritubular cells to come into close contact with Sertoli cells and subsequently to spread along the free surfaces of Sertoli cells. These conclusions and inferences are based on the following experiments. Cycloheximide-treated peritubular cells in culture in MEM containing cycloheximide readily attach to laminin-coated polystyrene surfaces. By contrast, added peritubular cells do not attach onto monolayers of Sertoli cells in monoculture or onto Sertoli cells plated on top of peritubular cells and maintained in coculture for periods of up to 48 h. In cocultures maintained for 6 days, however, labeled peritubular cells readily adhere to the free surfaces of reaggregated Sertoli cells. Laminin, but not fibronectin, appears on the free surfaces of the reaggregated Sertoli cells at this time, coinciding with the period of initial mound formation. The addition of antilaminin IgG, but not antifibronectin IgG, blocks the attachment of cycloheximide-treated peritubular cells to laminin-coated plates and also blocks the subsequent migration of peritubular cells required to form a monolayer. Similarly, anti-laminin IgG inhibits the attachment and spreading of labeled peritubular cells seeded on the free surfaces of reaggregated Sertoli cells in mounds generated during the morphogenetic cascade. We interpret the combined data to indicate that the appearance of laminin on the free surfaces of Sertoli cells is required to permit peritubular cells to adhere and subsequently to migrate on Sertoli cell surfaces, resulting in the formation of a tubule-like structure.


Stronger cortisol response to acute psychosocial stress is correlated with larger decrease in temporal sensitivity.
As a fundamental dimension of cognition and behavior, time perception has been found to be sensitive to stress. However, how one's time perception changes with responses to stress is still unclear. The present study aimed to investigate the relationship between stress-induced cortisol response and time perception. A group of 40 healthy young male adults performed a temporal bisection task before and after the Trier Social Stress Test for a stress condition. A control group of 27 male participants completed the same time perception task without stress induction. In the temporal bisection task, participants were first presented with short (400 ms) and long (1,600 ms) visual signals serving as anchor durations and then required to judge whether the intermediate probe durations were more similar to the short or the long anchor. The bisection point and Weber ratio were calculated and indicated the subjective duration and the temporal sensitivity, respectively. Data showed that participants in the stress group had significantly increased salivary cortisol levels, heart rates, and negative affects compared with those in the control group. The results did not show significant group differences for the subjective duration or the temporal sensitivity. However, the results showed a significant positive correlation between stress-induced cortisol responses and decreases in temporal sensitivity indexed by increases in the Weber ratio. This correlation was not observed for the control group. Changes in subjective duration indexed by temporal bisection points were not correlated with cortisol reactivity in both the groups. In conclusion, the present study found that although no significant change was observed in time perception after an acute stressor on the group-level comparison (i.e., stress vs. nonstress group), individuals with stronger cortisol responses to stress showed a larger decrease in temporal sensitivity. This finding may provide insight into the understanding of the relationship between stress and temporal sensitivity.


The exploration of N6-deoxyadenosine methylation in mammalian genomes.
N6-methyladenine (N6-mA, m6dA, or 6mA), a prevalent DNA modification in prokaryotes, has recently been identified in higher eukaryotes, including mammals. Although 6mA has been well-studied in prokaryotes, the function and regulatory mechanism of 6mA in eukaryotes are still poorly understood. Recent studies indicate that 6mA can serve as an epigenetic mark and play critical roles in various biological processes, from transposable-element suppression to environmental stress response. Here, we review the significant advances in methodology for 6mA detection and major progress in understanding the regulation and function of this non-canonical DNA methylation in eukaryotes, predominantly mammals.


Five-Year Incidence of Amyotrophic Lateral Sclerosis in British Columbia (2010-2015).
Amyotrophic lateral sclerosis (ALS) is a fatal degenerative neurological disease with significant effects on quality of life. International studies continue to provide consistent incidence values, though complete case ascertainment remains a challenge. The Canadian population has been understudied, and there are currently no quantitative data on the incidence of ALS in British Columbia (BC). The objectives of this study were to determine the five-year incidence rates of ALS in BC and to characterize the demographic patterns of the disease. The capture-recapture method was employed to estimate ALS incidence over a five-year period (2010-2015). Two sources were used to identify ALS cases: one database from an ALS medical centre and another from a not-for-profit ALS organization. During this time period, there were 690 incident cases within the two sources. The capture-recapture method estimated 57 unobserved cases, corresponding to a crude five-year incidence rate of 3.29 cases per 100,000 (CI 95%=3.05-3.53). The mean age of diagnosis was 64.6 (CI 95%=59.7-69.4), with 63.5 (CI 95%=56.9-70.1) for men and 65.7 (CI 95%=58.6-72.7) for women. There was a slight male preponderance in incidence, with a 1.05:1 ratio to females. Peak numbers in incidence occurred between the ages of 70 and 79. The incidence of ALS in BC was found to be consistent with international findings though nominally higher than that in other Canadian provinces to date.


Pain management via Ultrasound-guided Nerve Block in Emergency Department; a Case Series Study.
Pain is the most common complaint of patients referring to emergency department (ED). Considering the importance of pain management in ED, this study aimed to investigate the efficacy and feasibility of ultrasound-guided nerve blocks in this setting. 46 patients who came to the ED with injured extremities were enrolled in the study and received either femoral, axillary or sciatic nerve block depending on their site of injury (1.5 mg Bupivacaine per kg of patient's weight). Patients were asked about their level of pain before and after receiving the nerve block based on numerical rating scale. The difference between pre and post block pain severity was measured. Both patients and physicians were asked about their satisfaction with the nerve block in 5 tiered Likert scale. 46 patients with the mean age of 37.5 ± 12.5 years (8-82 years) received ultrasound-guided nerve block (84.8% male). 6 Sciatic, 25 axillary, and 15 femoral nerve blocks were performed. Mean pain severity on NRS score at the time of admission was 8.1 ± 1.4, which reduced to 2.04 ± 2.06 after block. 25 (54.3%) patients were highly satisfied (Likert scale 5), 15 (32.6%) were satisfied (Likert scale 4), 3 (6.5%) were neutral and had no opinion (Likert scale 3), 1 (2.1%) was not satisfied (Likert scale 2), and 2 (4.3%) were highly unsatisfied (Likert scale 1). There was no significant difference among the satisfaction scores within the three block locations (p = 0.8). There was no significant difference in physicians' level of satisfaction between the three block locations either (p = 0.9). 1 (2.1%) case of agitation and tachycardia and 1 (2.1%) case of vomiting were observed after the procedure. Ultrasound-guided nerve block of extremities is a safe and effective method that can be used for pain management in the ED. It results in high levels of satisfaction among both patients and physicians.


Metal Selenides as Efficient Counter Electrodes for Dye-Sensitized Solar Cells.
Solar energy is the most abundant renewable energy available to the earth and can meet the energy needs of humankind, but efficient conversion of solar energy to electricity is an urgent issue of scientific research. As the third-generation photovoltaic technology, dye-sensitized solar cells (DSSCs) have gained great attention since the landmark efficiency of ∼7% reported by O'Regan and Grätzel. The most attractive features of DSSCs include low cost, simple manufacturing processes, medium-purity materials, and theoretically high power conversion efficiencies. As one of the key materials in DSSCs, the counter electrode (CE) plays a crucial role in completing the electric circuit by catalyzing the reduction of the oxidized state to the reduced state for a redox couple (e.g., I3-/I-) in the electrolyte at the CE-electrolyte interface. To lower the cost caused by the typically used Pt CE, which restricts the large-scale application because of its low reserves and high price, great effort has been made to develop new CE materials alternative to Pt. A lot of Pt-free electrocatalysts, such as carbon materials, inorganic compounds, conductive polymers, and their composites with good electrocatalytic activity, have been applied as CEs in DSSCs in the past years. Metal selenides have been widely used as electrocatalysts for the oxygen reduction reaction and light-harvesting materials for solar cells. Our group first expanded their applications to the DSSC field by using in situ-grown Co0.85Se nanosheet and Ni0.85Se nanoparticle films as CEs. This finding has inspired extensive studies on developing new metal selenides in order to seek more efficient CE materials for low-cost DSSCs, and a lot of meaningful results have been achieved in the past years. In this Account, we summarize recent advances in binary and mutinary metal selenides applied as CEs in DSSCs. The synthetic methods for metal selenides with various morphologies and stoichiometric ratios and deposition methods for CE films are described. We emphasize that the in situ growth method exhibits advantages over other methods for fabricating stable and efficient CEs. We focus on the effect of morphology on the electocatalytic and photovoltaic performance. Application of transparent metal selenide CEs in bifacial DSSCs and the superiority of in situ-grown metal selenide nanosheet fiber CEs used for fiber DSSCs are presented. In addition, we show that metal selenides with a hollow sphere structure can function not only as an efficient electrocatalyst but also as a light-scattering layer. Finally, we present our views on the current challenges and future development of metal selenide CE materials.


Functional reconstruction of exstrophied bladder. Timing and technique. Follow-up of 39 cases.
Thirty-nine cases of functional reconstruction of exstrophied bladder are reviewed. There were 20 females and 19 males. In a first group of 31 staging was planned and carried out in 26 while 3 are awaiting a second stage. In a second group of 8 a single operation was performed. Out of the 31 early cases there were 2 deaths and 10 failures, 16 show good or very good functional result. All 16 show moderate renal scarring from reflux pyelonephritis which occurred between I and II stage. Single operation consisted of innominate osteotomy, bladder and bladder neck and urethral reconstruction and anti-reflux procedure (osteotomy was omitted in a 3 days old baby). Three, operated upon when aged 8 mths., 1 year and 4 years, were breakdowns of previous closure. They are incontinent and will need further surgery at the bladder outlet. Four are dry in the morning and suffer from occasional stress incontinence and enuresis. One, now aged 4 years, still wears pads. These last 5 are awaiting final assessment of and eventually further surgery to improve continence. In all 8 cases pyelo-calyceal cavities are normal except for a moderate right dilatation in one because of kinking of the reimplanted ureter. Delay in bladder closure (mean age 5 mths.) and severe changes to the bladder wall and possibly staging seems to be responsible for most of the failures and for renal damage occurring, after closure, in bladders showing moderate compliance. Single operation allows full protection of upper tract and kidney and should be preferred in patients aged over 2 months. Better functional results may be obtained if operation is performed soon after birth.


[Chromocenter organization in salivary glands of the malaria mosquito Anopheles messeae Fall].
The chromocenter organization and the relationship with the nuclear envelope were studied in Anopheles messeae Fall. malaria mosquito. The interchromosomal contacts within the chromocenter were shown to be formed by both alpha- and beta-heterochromatin. In the pericentric regions of all chromosomes and in highly repeated sequences localized mostly in alpha-heterochromatin, the incorporation of the moderate He-T repeat of D. melanogaster was also found. Each chromosome was shown to have an independent contact to the nuclear envelope via certain beta-heterochromatin loci. The morphology of the Y chromosome, which is also capable of forming ectopic contacts within the chromocenter boundaries, was studied.


Surface-Initiated Initiators for Continuous Activator Regeneration (SI ICAR) ATRP of MMA from 2,2,6,6-tetramethylpiperidine-1-oxy (TEMPO) Oxidized Cellulose Nanofibers for the Preparations of PMMA Nanocomposites.
An effective method of oxidation from paper pulps via 2,2,6,6-tetramethylpiperidine-1-oxy (TEMPO) compound to obtain TEMPO-oxidized cellulose nanofibers (TOCNs) was demonstrated. Following by acylation, TOCN having an atom transfer radical polymerization (ATRP) initiating site of bromoisobutyryl moiety (i.e., TOCN-Br) was successfully obtained. Through a facile and practical technique of surface-initiated initiators for continuous activator regeneration atom transfer radical polymerization (SI ICAR ATRP) of methyl methacrylate (MMA) from TOCN-Br, controllable grafting polymer chain lengths (Mn = ca. 10k-30k g/mol) with low polydispersity (PDI < 1.2) can be achieved to afford TOCN-g-Poly(methyl methacrylate) (PMMA) nanomaterials. These modifications were monitored by Fourier-transform infrared spectroscopy (FT-IR), scanning electron microscopy (SEM), electron spectroscopy for chemical analysis (ESCA), and water contact angle analysis. Eventually, TOCN-g-PMMA/PMMA composites were prepared using the solvent blending method. Compared to the pristine PMMA (Tg = 100 °C; tensile strength (σT) = 17.1 MPa), the composites possessed high transparency with enhanced thermal properties and high tensile strength (Tg = 110 °C and σT = 37.2 MPa in 1 wt% TOCN containing case) that were investigated by ultraviolet-visible spectroscopy (UV-Vis), thermogravimetric analysis (TGA), dynamic mechanical analysis (DMA), and tensile tests. We demonstrated that minor amounts of TOCN-g-PMMA nanofillers can provide high efficacy in improving the mechanical and thermal properties of PMMA matrix.


An appropriate Wnt/β-catenin expression level during the remodeling phase is required for improved bone fracture healing in mice.
Accumulating evidence demonstrates that the Wnt/β-catenin signaling pathway plays a dominant role in bone repair. However, the role of Wnt/β-catenin signaling in the remodeling phase during bone fracture healing is currently unknown. In the present study, β-catenin was activated at different levels or deleted in mice at the late stage of fracture healing, and the effects on healing quality were investigated. Deletion of β-catenin disturbed bone remodeling, as confirmed by increased bone resorption and decreased bone formation, and significantly decreased bone strength compared with wildtype mice. In addition, the constitutive activation of β-catenin significantly increased the bone mass and delayed the bone remodeling process, resulting in slightly impaired bone strength. In contrast, a slight activation of β-catenin significantly increased bone formation and slightly hindered bone resorption. These effects lead to improved bone fracture healing quality compared with wildtype mice. In summary, the present study provides the first demonstration showing that Wnt/β-catenin signaling should be maintained at a slightly activated level during the late stage of fracture healing to ensure better bone fracture repair.


[Hydroxyethyl starch--an interim report].
Since the beginning of this century, a few biopolymers have been used as basic materials for volume substitution. Aside from gelatin and dextran, modified starch (hydroxyethyl starch, HES) is currently the first-choice means. Due to special manufacturing processes, different hydroxyethyl starches are now available. They have several different characteristics and produce different clinical effects. These clinical properties depend on the average molecular weight and the distribution of molecular weight as well as on the degree and pattern of substitution. The duration of volume effect, one of the most important parameters for the effectiveness of a volume substitute, depends to a large degree on the substitution. Elimination of HES from serum is delayed by a high degree of substitution and a high C2/C6 ratio of the substitution pattern. The molecular parameters of HES also influence other effects, such as cumulation in various organs and hemostasis. Critical reading of current HES literature shows that many questions still have to be answered. At the same time ways and means of optimizing differential volume substitution therapy and hemodilution therapy are emerging.


4-Amidinoindan-1-one 2'-amidinohydrazone: a new potent and selective inhibitor of S-Adenosylmethionine decarboxylase.
Two isomeric amidino-2-acetylpyridine amidinohydrazones, 11 and 12, and 4-amidinoindanone amidinohydrazone, 17, have been synthesized and tested for inhibition of S-adenosylmethionine decarboxylase (SAMDC) and diamine oxidase and for antiproliferative activity against T24 human bladder carcinoma cells. Compound 11 inhibited SAMDC with an IC50 of 10 nM and was 140- and > 500-fold more potent than methylglyoxal bis(guanylhydrazone) (MGBG) and 12, respectively. The difference in potency between 11 and 12 was interpreted with the help of molecular modeling and appeared to be associated with two different low-energy conformations of the compounds. Compound 17 which represents a conformationally constrained analogue of 11, was superior to the latter and MGBG with respect to selective inhibition of SAMDC and antiproliferative activity, and is of interest as a potential anticancer agent and a drug for the treatment of protozoal and Pneumocystis carinii infections.


Polymorphism of MDM2 promoter 309 (rs 2279744) and the risk of PCOS.
This study aimed at evaluating possible association between MDM2 SNP309 polymorphism (rs 2279744) and polycystic ovary syndrome (PCOS). One hundred and twenty-five women with PCOS and two hundred and fifty women without PCOS were collected from the department of reproductive medicine of college hospital in this case-control study. Peripheral blood samples were collected from all participants and DNA was extracted, MDM2 SNP309 polymorphism (rs 2279744) was determined from the 125 cases and 250 controls. Women were grouped into PCOS (n = 125) group and control group (n = 250). Odds ratios (OR) and 95% confidence intervals (CI) were used to evaluate the association between MDM2 SNP309 polymorphism (rs 2279744) and PCOS. The distribution of T allele was significant higher in PCOS cases than controls. MDM2 SNP 309 T allele is associated with PCOS.


Dose-incidence relationships derived from superposition of distributions of individual susceptibility on mechanism-based dose responses for biological effects.
Dose-response relationships for incidence are based on quantal response measures. A defined effect is either present or not present in an individual. The dose-incidence curve therefore reflects differences in individual susceptibility (the "tolerance distribution"). At low dose, only the more susceptible individuals manifest the effect, while higher doses are required for more resistant individuals to be recruited into the affected fraction of the group. Here, we analyze how such dose-incidence relationships are related to mechanism-based dose-response relationships for biological effects described on a continuous scale. As an example, we use the quantal effect "cell division" triggered by occupancy of growth factor receptors (R) by a hormone or mitogenic ligand (L). The biologically effective dose (BED) is receptor occupancy (RL). The dose-BED relationship is described by the hyperbolic Michaelis-Menten function, RL/Rtot = L / (L + K(D)). For the conversion of the dose-BED relationship to a dose-cell division relationship, the dose-BED curve has to be combined with a function that describes the distribution of susceptibilities among the cells to be triggered into mitosis. We assumed a symmetrical sigmoid curve for this function, approximated by a truncated normal distribution. Because of the supralinear dose-BED relationship due to the asymptotic saturation of the Michaelis-Menten function, the composite curve that describes cell division (incidence) as a function of dose becomes skewed to the right. Logarithmic transformation of the dose axis reverses this skewing and provides a nearly perfect fit to a normal distribution in the central 95% incidence range. This observation may explain why dose-incidence relationships can often be described by a cumulative normal curve using the logarithm of the administered dose. The dominant role of the tolerance distribution for dose-incidence relationships is also illustrated with the example of a linear dose-BED relationship, using adducts to protein or DNA as the BED. Superimposed by a sigmoid distribution of individual susceptibilities, a sigmoid dose-incidence curve results. Linearity is no longer observed. We conclude that differences in susceptibility should always be considered for toxicological risk assessment and extrapolation to low dose.


Health economic modeling of the potential cost saving effects of Neurally Adjusted Ventilator Assist.
Asynchrony between patient and ventilator breaths is associated with increased duration of mechanical ventilation (MV). Neurally Adjusted Ventilatory Assist (NAVA) controls MV through an esophageal reading of diaphragm electrical activity via a nasogastric tube mounted with electrode rings. NAVA has been shown to decrease asynchrony in comparison to pressure support ventilation (PSV). The objective of this study was to conduct a health economic evaluation of NAVA compared with PSV. We developed a model based on an indirect link between improved synchrony with NAVA versus PSV and fewer days spent on MV in synchronous patients. Unit costs for MV were obtained from the Swedish intensive care unit register, and used in the model along with NAVA-specific costs. The importance of each parameter (proportion of asynchronous patients, costs, and average MV duration) for the overall results was evaluated through sensitivity analyses. Base case results showed that 21% of patients ventilated with NAVA were asynchronous versus 52% of patients receiving PSV. This equals an absolute difference of 31% and an average of 1.7 days less on MV and a total cost saving of US$7886 (including NAVA catheter costs). A breakeven analysis suggested that NAVA was cost effective compared with PSV given an absolute difference in the proportion of asynchronous patients greater than 2.5% (49.5% versus 52% asynchronous patients with NAVA and PSV, respectively). The base case results were stable to changes in parameters, such as difference in asynchrony, duration of ventilation and daily intensive care unit costs. This study showed economically favorable results for NAVA versus PSV. Our results show that only a minor decrease in the proportion of asynchronous patients with NAVA is needed for investments to pay off and generate savings. Future studies need to confirm this result by directly relating improved synchrony to the number of days on MV.


Tremors and chorea induced by trimethoprim-sulfamethoxazole in a child with Pneumocystis pneumonia.
A 1.5-year-old girl developed high frequency tremors and chorea after receiving a dose of 120 mg/kg/d trimethoprim-sulfamethoxazole (TMP-SMX) for the treatment of Pneumocystis pneumonia. The child was human immunodeficiency virus-negative but immunocompromised because of prolonged immunosuppressive therapy. These symptoms disappeared 3 days after TMP-SMX was discontinued. Pediatricians should be aware of tremors and chorea among the potential adverse effects of high doses of TMP-SMX.


Enhanced magnetization in highly crystalline and atomically mixed bcc Fe-Co nanoalloys prepared by hydrogen reduction of oxide composites.
Fe(x)Co(100-x) nanoalloys (NAs) with 20 ≤ x ≤ 80 were prepared by hydrogen reduction of Fe-Co oxide nano-composites, which were composed of mixed phases (or domains) of Fe(2)O(3) and CoO. In situ X-ray diffraction (XRD) measurements using synchrotron radiation clearly showed development of a solid-solution Fe-Co phase by hydrogen reduction from the oxide composites. High-resolution transmission electron microscopy (TEM), high-angle annular dark-field scanning TEM and powder XRD revealed that Fe-Co NAs form a single crystal structure and the two elements are mixed homogeneously. The saturation magnetization depends on the size and metal composition and shows the highest value (250 emu g(-1)) for the Fe(70)Co(30) NA in the size range of 30-55 nm, which is comparable to that of the Fe(70)Co(30) bulk alloy (245 emu g(-1)). This high magnetization is attributable to high crystallinity and homogeneous mixing of constituent atoms, which are attained by thermal treatment of oxide phases under a hydrogen atmosphere.


Do interictal microembolic signals play a role in higher cortical dysfunction during migraine aura?
The aim of this study was to evaluate the prevalence and clinical impact of interictal microembolic signals (MES) in patients suffering from migraine with higher cortical dysfunction (HCD), such as language and memory impairment, during an aura. This study was carried out on 34 migraineurs with language and memory impairment during aura (HCD group), 31 migraineurs with only visual or visual and somatosensory symptoms during aura (Control group I), and 34 healthy controls (Control group II). We used a Doppler instrument to detect microemboli. Demographic data, disease features and the detection of MES between these groups, as well as the predictors of HCD during the aura, were analyzed. The duration of aura was longer and the frequency of aura was higher among patients with language and memory impairment during aura compared to Control group I. MES was detected in 29.4% patients from the HCD group, which was significantly higher compared to 3.2% in Control group I and 5.9% in Control group II. Regarding the absence or presence of MES, demographic and aura features were not different in the HCD subgroups. A longer duration of aura, the presence of somatosensory symptoms during the aura and the presence of interictal MES were independent predictors of HCD during the aura. The present findings indicate that HCD and MES are related in patients with migraine with aura. Further research is needed to better understand the exact pathophysiological mechanism.


Benefits and risks of P2Y12 inhibitor preloading in patients with acute coronary syndrome and stable angina.
Treatment with P2Y12 inhibitors is an integral part of the standard of care for patients undergoing percutaneous coronary intervention. However, the most appropriate timing for P2Y12 inhibitor administration remains unclear, and the value of "preloading" with P2Y12 inhibitors prior to cardiac catheterization is controversial. While pre-catheterization treatment with P2Y12 inhibitors is performed with the goal of decreasing adverse cardiovascular events, this potential benefit must be weighed against the increased risk of bleeding complications and operative delay if coronary artery bypass graft surgery is indicated. A number of studies have been conducted to evaluate the utility of preloading with P2Y12 inhibitors prior to cardiac catheterization for varying indications including stable angina and acute coronary syndrome (ACS). In this article, we review the literature and discuss the advantages and disadvantages of the preloading strategy. Several individual studies offer inconclusive and even conflicting findings. However, when taken in sum, these studies allow for several conclusions about the utility of P2Y12 inhibitor pretreatment. The existing literature demonstrate that preloading is associated with some degree of reduction in adverse ischemic events, although this benefit comes with an increased risk of bleeding complications. The appropriateness of preloading therefore varies based on the indication for catheterization, likely justified in patients with ACS but unlikely to benefit patients with stable angina.


[Military telemedicine: a network of networks].
Military telemedicine is a form of collaborative medicine based on the use of communication and information networks. It is more a network of networks than of independent systems. It comprises electronic medical files, epidemiological networks, and surgical and medical databases. Each system must be able to communicate with the others, thereby enabling the development of remote consultation, expertise and assistance. This requires networking between the army, the navy, and the air force communication networks, especially during special operations conducted abroad. We must also develop interoperability with systems in other countries, and with the French civilian health service. This means respecting the general rules governing these networks. The military health network is unique, in that it focuses on battlefield injuries. In addition, the French military health service operates under a single headquarters, governing nurses, paramedics and physicians.


Antimicrobial, Antioxidant and Cytotoxic Activity of Silver Nanoparticles Synthesized by Leaf Extract of Erythrina suberosa (Roxb.).
In this experiment, biosynthesized silver nanoparticles (AgNPs) were synthesized using aqueous leaf extract of Erythrina suberosa (Roxb.). The biosynthesis of silver nanoparticle was continuously followed by UV-vis spectrophotometric analysis. The response of the phytoconstituents resides in E. suberusa during synthesis of stable AgNPs were analyzed by ATR- fourier-transform infrared spectroscopy. Further, the size, charge, and polydispersity nature of AgNPs were studied using dynamic light scattering spectroscopy. The morphology of the nanoparticles was determined by scanning electron microscopy. Current result shows core involvement of plant extracts containing glycosides, flavonoids, and phenolic compounds played a crucial role in the biosynthesis of AgNPs. The antimicrobial activities of silver nanoparticles were evaluated against different pathogenic bacterium and fungi. The antioxidant property was studied by radical scavenging (DPPH) assay and cytotoxic activity was evaluated against A-431 osteosarcoma cell line by MTT assay. The characteristics of the synthesized silver nanoparticles suggest their application as a potential antimicrobial and anticancer agent.


Feasibility of supracricoid laryngectomy based on pathological examination.
Partial horizontal supracricoid laryngectomy with cricohyoidopexy at the Department of Otolaryngology, Medical University of Białystok, involves resection of the entire thyroid cartilage with the pre-epiglottic and paraglottic spaces. Experience has shown that this technique will permit adequate phonation, respiration and deglutition in selected advanced cases of supraglottic and glottic carcinoma. The purpose of this study was to verify histologically the indications for this surgery by examining sections of whole-organ laryngeal specimens. Post-laryngectomy specimens from 90 patients with otherwise previously untreated supraglottic (48), transglottic (22) and glottic (20) carcinomas were reviewed retrospectively. The majority (66) of the specimens were staged as pT4. Findings showed that 22 of the specimens analyzed (mostly supraglottic tumors) could have been eradicated by supracricoid laryngectomy alone. The present study confirmed the principles of supracricoid laryngectomy for selected large tumors.


10 μm thick ultrathin glass sheet to realize a highly sensitive cantilever for precise cell stiffness measurement.
The micro-cantilever-based sensor platform has become a promising technique in the sensing area for physical, chemical and biological detection due to its portability, small size, label-free characteristics and good compatibility with "lab-on-a-chip" devices. However, traditional micro-cantilever methods are limited by their complicated fabrication, manipulation and detection, and low sensitivity. In this research, we proposed a 10 μm thick ultrathin, highly sensitive, and flexible glass cantilever integrated with a strain gauge sensor and presented its application for the measurement of single-cell mechanical properties. Compared to conventional methods, the proposed ultrathin glass sheet (UTGS)-based cantilever is easier to fabricate, has better physical and chemical properties, and shows a high linear relationship between resistance change and applied small force or displacement. The sensitivity of the cantilever is 15 μN μm-1 and the minimum detectable displacement at the current development stage is 500 nm, which is sufficient for cell stiffness measurement. The cantilever also possesses excellent optical transparency that supports real-time observation during measurement. We first calibrated the cantilever by measuring the Young's modulus of PDMS with known specific stiffness, and then we demonstrated the measurement of Xenopus oocytes and fertilized eggs in different statuses. By further optimizing the UTGS-based cantilever, we can extend its applicability to various measurements of different cells.


Studies of the metabolic activity of leukocytes from patients with a genetic abnormality of phagocytic function.
Polymorphonuclear leukocytes from patients with chronic granulomatous disease respond to the phagocytosis of latex particles with normal increments in glucose consumption, lactate production, Krebs' cycle activity, and lipid turnover. The leukocytes of these patients fail to show normal increments in respiration, direct oxidation of glucose, and hydrogen peroxide formation during particle uptake. It appears that the stimulation of respiration with the formation of hydrogen peroxide and stimulation of the direct oxidative pathway of glucose metabolism are closely linked to degranulation and intracellular killing of bacteria by polymorphonuclear leukocytes.


[Influences of lipid peroxidative injury to endothelial cells on adherence and migration of monocyte].
The influences of lipid peroxidative injury to endothelial cells (EC) on adherence to EC and migration into subendothelial space of human monocytes were studied by using a modified vascular endothelial model in vitro. Lipid peroxidative injury to cultured human umbilical vein EC was initiated by treating the EC with diamide. The results showed that injury to EC could enhance adherence to EC and migration into subendothelial space of monocytes. Monocytes mainly adhered to the intercellular space and surface of injured EC. In the area of EC denudation, the number of monocytes which migrate into the subendothelial space was more than that in the area without denudation. These results suggested that enhanced adherence to EC and migration into subendothelial space of monocytes caused by lipid peroxidative injury to EC may play an important role in atherogenesis.


Red cell volume can be accurately determined in sheep using a nonradioactive biotin label.
The sheep has served as an informative animal model for investigation of human fetal and newborn erythropoiesis and red blood cell (RBC) kinetics. We previously validated the permanent label (14C)cyanate for measuring red cell volume (RCV) in sheep. Here, we validate biotin labeling of RBCs as a nonradioactive method for measuring RCV in sheep with the anticipation that it can be applied in studies of human infants. The RCV was determined simultaneously using two techniques for quantitation of the biotin label. The first one quantified total blood concentration of biotin label on biotin-labeled RBCs using (125I)streptavidin. The second one enumerated biotin-labeled RBCs by flow cytometry after incubation with fluorescein-conjugated avidin. RCV measurements made using the two biotin quantitation techniques were validated against both (14C)cyanate and 51Cr as reference methods. Both biotin techniques produced RCV values that agreed well with the reference methods and with each other, producing correlation coefficients averaging >or =0.93. Sequential repetitive measurements in the same animal also agreed with the (14C)cyanate method and each other (average difference <10%). These results establish biotin-labeled RBCs as an accurate method for performing RCV measurements in sheep. This biotin method can be applied in studies that model neonatal erythropoiesis.


Characteristics of verotoxigenic Escherichia coli from pigs.
Porcine verotoxigenic Escherichia coli were characterized with respect to frequency of occurrence, serogroup, and association with disease, weaning, and selected properties of the bacterium. Of 668 strains of E. coli from southern Ontario pigs with enteric disease, 32 (4.8%) produced verotoxin at 10(3)-10(7) cytotoxic doses per mL of culture supernatant. Of 22 isolates which belonged to O serogroups 138, 139 and 141, 15 produced verotoxin. Among other enterotoxigenic types of E. coli, two of 57 isolates of O157:K"V17" and two of 96 isolates of O149:K91 were verotoxigenic. The remaining 13 verotoxigenic E. coli belonged to O groups 2, 107, 120, 121 and 130. An additional 21 verotoxigenic E. coli belonging to O groups 138, 139 and 141 and three to O157:K"V17" were identified in a collection of 47 E. coli recovered from weaned pigs with enteric disease. Verotoxigenic E. coli were associated with postweaning diarrhea, bloody stools, sudden death and edema disease. They were isolated at similar frequencies (14%) from healthy weaned pigs, and from weaned pigs with enteric disease. Isolation rates from neonates were low and significantly different from rates in weaned pigs. Neutralizing antibody to verotoxin was not detected in the sera of 45 pigs, which included pigs from herds with a history of edema disease. Verotoxin was not associated with production of colicin, hemolysin, or enterotoxins or with any of 23 biochemical properties of the organisms. The serological data indicate that porcine verotoxigenic E. coli are not a common source of verotoxigenic E. coli for humans. Porcine verotoxin may play a role in postweaning diarrhea and absence of detectable neutralizing antibody in serum may be an important aspect of pathogenesis.


A case of chronic dissecting aortic aneurysm complicated with rupture into the right atrium: Diagnosis by transesophageal echocardiography.
Although rupture of a dissecting aortic aneurysm into the pericardial sac, pleural cavities, or mediastinum is a frequently encountered complication of this entity, rupture into a right-sided cardiac chamber is extremely rare. An 80-year-old woman was admitted to this institution because of dyspnea and facial edema. One year before admission, a diagnosis of dissecting aortic aneurysm (Stanford A type) was made based on results of magnetic resonance imaging and transesophageal echocardiography (TEE); however, the patient and her family refused surgical therapy. On admission, blood pressure was 120/60 mmHg, and a Levine 3/6° continuous murmur was audible at the third and fourth intercostal spaces of the right sternal border. Chest x-ray film showed moderate cardiomegaly, congested lung fields, and bilateral pleural effusion. A two-dimensional echocardiogram revealed severe aortic root dilatation 80 mm in diameter with the intimal flap. Color flow Doppler imaging demonstrated abnormal flow toward the back space in dilated ascending aorta. Continuous wave Doppler imaging showed the peak velocity of this flow to be 4.8 m/s. This high-velocity flow strongly suggested that the dissecting aortic aneurysm had ruptured into the right-sided cardiac chamber, and shunt flow from the false lumen of the aortic aneurysm into the right atrium was directly visualized by TEE. Our diagnosis, based on these findings, was chronic dissecting aortic aneurysm with communication into the right atrium. In view of the patient's deteriorating clinical condition, cardiac catheterization was not performed before surgery. Surgery revealed an aneurysm of the ascending aorta measuring 90 mm in diameter and multiple fistulas approximately 2 to 3 mm in diameter arising from the false lumen of the aorta into the right atrium at the base of the atrial appendage. The patient underwent successful replacement of the ascending aorta and closure of the aorto-right atrial fistulas. She had an uneventful postoperative course and was discharged 7 weeks after surgery.


Down-regulation of lncRNA DNAJC3-AS1 inhibits colon cancer via regulating miR-214-3p/LIVIN axis.
Long non-coding RNAs (lncRNAs) play a key role in the development and metastasis of cancer. However, the biological role and clinical significance of lncRNA DNAJC3-AS1 in the development of colon cancer is still unknown. In this study, the effects of DNAJC3-AS1 on cell proliferation, migration, and invasion were evaluated by MTT assay, wound-healing assay, and transwell assay, respectively. The relationship between DNAJC3-AS1, miR-214-3p and LIVIN was predicted by the online software and confirmed by dual-luciferase reporter assay. We found that the down-regulation of DNAJC3-AS1 inhibited the proliferation of colon cancer cells and induced growth arrest. Down-regulation of DNAJC3-AS1 also inhibited the migration, invasion, and epithelial-mesenchymal transition (EMT) of colon cancer cells. Moreover, miR-214-3p can bind to DNAJC3-AS1, and knockdown of DNAJC3-AS1 increased miR-214-3p expression in colon cancer cells. LIVIN was identified as a target of miR-214-3p. The up-regulation of miR-214-3p inhibited the protein expression of LIVIN and suppressed the activation of the NF-κB signaling pathway. Besides, down-regulation of DNAJC3-AS1 reduced cell viability, invasion, and EMT of colon cancer cells, while miR-214-3p inhibitor could reverse these effects. The expression of LIVIN and the activation of the NF-κB signaling pathway were suppressed by down-regulating DNAJC3-AS1, while these effects could be restored by miR-214-3p inhibitor. These findings suggested that DNAJC3-AS1 may promote colon cancer progression by regulating the miR-214-3p/LIVIN axis. DNAJC3-AS1 may serve as a new biomarker and therapeutic target for colon cancer, stimulating new research directions and treatment options.


Measuring dynamical systems on directed hypergraphs.
Networks and graphs provide a simple but effective model to a vast set of systems in which building blocks interact throughout pairwise interactions. Unfortunately, such models fail to describe all those systems in which building blocks interact at a higher order. Higher-order graphs provide us the right tools for the task, but introduce a higher computing complexity due to the interaction order. In this paper we analyze the interplay between the structure of a directed hypergraph and a linear dynamical system, a random walk, defined on it. How can one extend network measures, such as centrality or modularity, to this framework? Instead of redefining network measures through the hypergraph framework, with the consequent complexity boost, we will measure the dynamical system associated to it. This approach let us apply known measures to pairwise structures, such as the transition matrix, and determine a family of measures that are amenable to such a procedure.


Does extralaryngeal branching have an impact on the rate of postoperative transient or permanent recurrent laryngeal nerve palsy?
This prospective study assessed the prevalence of the extralaryngeal branching of the recurrent laryngeal nerve (RLN) and its impact on the incidence of postoperative transient or permanent RLN palsy. Total or hemithyroidectomy was performed in 115 patients, with a total of 195 RLNs displayed. The RLN extralaryngeal branches were routinely identified and preserved. The postoperative course of each patient was evaluated. Outcomes of patients with and without branching RLN were compared. In all, 36 of 195 (18.5%) nerves showed extralaryngeal branching: 27 cases (25.5%) on the right and 9 on the left side (10.1%; p = 0.0088).Trifurcation of the RLN was identified in two dissections (1%). Bilateral bifurcations were observed in 3 of 80 (3.7%) patients. We reported four (2.1%) unilateral permanent RLN palsies, eight cases of unilateral transient nerve palsy (4.1%), and one bilateral transient RLN injury (0.6%). The comparative analysis of postoperative outcomes between branched and nonbranched RLNs revealed that the anatomical variation was more frequently associated both with unilateral permanent RLN palsy (relative risk, 13.25; 95% confidence interval, 1.42-123.73; p = 0.0204) and unilateral transient RLN palsy (relative risk, 7.36; 95% confidence interval, 1.84-29.4; p = 0.0061). The only case of bilateral transient RLN injury was associated with a nonrecurrent inferior laryngeal nerve. Branched RLNs represent a risk factor both for transient and permanent nerve palsy after surgery. Awareness of this anatomical variation and its routine investigation are essential during thyroid surgery to limit its relevant impact on postoperative RLN injury rate.


Alternative Pre-mRNA Splicing in Mammals and Teleost Fish: A Effective Strategy for the Regulation of Immune Responses Against Pathogen Infection.
Pre-mRNA splicing is the process by which introns are removed and the protein coding elements assembled into mature mRNAs. Alternative pre-mRNA splicing provides an important source of transcriptome and proteome complexity through selectively joining different coding elements to form mRNAs, which encode proteins with similar or distinct functions. In mammals, previous studies have shown the role of alternative splicing in regulating the function of the immune system, especially in the regulation of T-cell activation and function. As lower vertebrates, teleost fish mainly rely on a large family of pattern recognition receptors (PRRs) to recognize pathogen-associated molecular patterns (PAMPs) from various invading pathogens. In this review, we summarize recent advances in our understanding of alternative splicing of piscine PRRs including peptidoglycan recognition proteins (PGRPs), nucleotide binding and oligomerization domain (NOD)-like receptors (NLRs), retinoic acid-inducible gene-I (RIG-I)-like receptors (RLRs) and their downstream signaling molecules, compared to splicing in mammals. We also discuss what is known and unknown about the function of splicing isoforms in the innate immune responses against pathogens infection in mammals and teleost fish. Finally, we highlight the consequences of alternative splicing in the innate immune system and give our view of important directions for future studies.


[Incidence and impact of HIV infection among patients with bacterial pleurisy in Lomé (Togo)].
A prospective study was made in the Tokoin university hospital in Lomé (Togo) to determine the incidence and the impact of HIV among patients with bacterial pleurisy. Two hundred cases of bacterial pleurisy were consecutively included over 17 months. The HIV diagnostic was performed using ELISA (Vironostika HIV Uni-Form II plus O and HIV1 and 2 Bispot Immunocomb II). The 200 cases of pleurisy included 152 (76%) tuberculous pleural effusion and 48 (24%) pleural empyema. Staphylococcus aureus (32%), Streptococcus pneumoniae (14.9%), and Pseudomonas (14.9%) were the main causes of pleural empyema. The HIV incidence was 61% (122/200). The mortality rate ranged from 26.2% in the HIV positive group to 5.1% in HIV negative group (P = 0.0001). The bacterial aspect of pleural empyema was heterogeneous in both groups but Salmonella Enteritidis and Salmonella Typhimurium were identified only among patients with HIV.


Fast determination of Ziziphora tenuior L. essential oil by inorganic-organic hybrid material based on ZnO nanoparticles anchored to a composite made from polythiophene and hexagonally ordered silica.
In this paper, for the first time, an inorganic-organic hybrid material based on ZnO nanoparticles was anchored to a composite made from polythiophene and hexagonally ordered silica (ZnO/PT/SBA-15) for use in solid-phase fibre microextraction (SPME) of medicinal plants. A homemade SPME apparatus was used for the extraction of volatile components of Ziziphora tenuior L. A simplex method was used for optimisation of five different parameters affecting the efficiency of the extraction. The main constituents extracted by ZnO/PT/SBA-15 and PDMS fibres and hydrodistillation (HD) methods, respectively, included pulegone (51.25%, 53.64% and 56.68%), limonene (6.73%, 6.58% and 8.3%), caryophyllene oxide (5.33%, 4.31% and 4.53%) and 1,8-cineole (4.21%, 3.31% and 3.18%). In comparison with the HD method, the proposed technique could equally monitor almost all the components of the sample, in an easier way, in a shorter time and requiring a much lower amount of the sample.


The Continued Promise and Many Disappointments of Oncolytic Virotherapy in Gastrointestinal Malignancies.
Oncolytic virotherapy represents a novel therapeutic strategy in the treatment of gastrointestinal malignancies. Oncolytic viruses, including genetically engineered and naturally occurring viruses, can selectively replicate in and induce tumor cell apoptosis without harming normal tissues, thus offering a promising tool in the armamentarium for cancer therapy. While this approach has garnered much interest over the past several decades, there has not been significant headway across various tumor types. The recent approval of talimogene laherparepvec, a second-generation oncolytic herpes simplex virus type-1, for the treatment of metastatic melanoma, confirms the therapeutic potential of oncolytic viral therapy. Herein, we will highlight and review the role of oncolytic viral therapy in gastrointestinal malignancies while discussing its limitations and potential alternative mechanisms to improve its treatment efficacy.


Adrenal Pheochromocytoma Incidentally Discovered in a Patient With Parkinsonism.
To evaluate the diagnostic route of pheochromocytoma (PHEO) in a patient under dopaminergic treatment.A 70-year-old man with Parkinsonism and under treatment with levodopa and carbidopa came to our observation for evaluation of arterial hypertension and right adrenal mass discovered incidentally.To evaluate adrenal hormone levels we performed a dexamethasone suppression test, plasma aldosterone levels and 24-hr urinary metanephrine, which revealed elevated levels of catecholamines metabolities. 123-I-metaiodobenzylguanidine SPECT scintiscan revealed raised activity within the right adrenal gland concordant with the mass. The diagnosis of PHEO was posed and an elective laparoscopic adrenalectomy was performed; histopathological examination confirmed the PHEO diagnosis.Recently the coexistence of PHEO and Parkinsonism is a very rare association of diseases, with only 3 cases reported in literature. In this article, another case is reported and diagnostic procedures are discussed.


Retention of African American Women in a Lifestyle Physical Activity Program.
The purpose of the article is to examine how well individual characteristics, neighborhood characteristics, and intervention participation predict study retention and staff level of effort needed for retention, using a cohort of African American women enrolled in a physical activity program. Secondary data analysis was conducted from a randomized clinical trial. Participants were aged 40 to 65 years without major signs/symptoms of cardiovascular disease. Assessments were conducted at community sites in/bordering African American communities. Study retention was 90%. Of those retained, 24% required moderate/high level of staff effort for retention. Retention was predicted by being older, having lower perceived neighborhood walkability, living in neighborhoods with greater disadvantage and crime, and having greater program participation. More staff effort was predicted by participants being younger, having more economic hardships, poorer health, or lower intervention participation. We may be able to identify people at baseline likely to require more staff effort to retain.


Dispersion interactions of carbohydrates with condensate aromatic moieties: theoretical study on the CH-π interaction additive properties.
In this article we present the first systematic study of the additive properties (i.e. degree of additivity) of the carbohydrate-aromatic moiety CH-π dispersion interaction. The additive properties were studied on the β-D-glucopyranose, β-D-mannopyranose and α-L-fucopyranose complexes with the naphthalene molecule by comparing the monodentate (single CH-π) and bidentate (two CH-π) complexes. All model complexes were optimized using the DFT-D approach, at the BP/def2-TZVPP level of theory. The interaction energies were refined using single point calculations at highly correlated ab initio methods at the CCSD(T)/CBS level, calculated as E + (E(CCSD(T))-E(MP2))(Small Basis). Bidentate complexes show very strong interactions in the range from -10.79 up to -7.15 and -8.20 up to -6.14 kcal mol(-1) for the DFT-D and CCSD(T)/CBS level, respectively. These values were compared with the sum of interaction energies of the appropriate monodentate carbohydrate-naphthalene complexes. The comparison reveals that the bidentate complex interaction energy is higher (interaction is weaker) than the sum of monodentate complex interaction energies. Bidentate complex interaction energy corresponds to 2/3 of the sum of the appropriate monodentate complex interaction energies (averaging over all modeled carbohydrate complexes). The observed interaction energies were also compared with the sum of interaction energies of the corresponding previously published carbohydrate-benzene complexes. Also in this case the interaction energy of the bidentate complex was higher (i.e. weaker interaction) than the sum of interaction energies of the corresponding benzene complexes. However, the obtained difference is lower than before, while the bidentate complex interaction energy corresponds to 4/5 of the sum of interaction energy of the benzene complexes, averaged over all structures. The mentioned comparison might aid protein engineering efforts where amino acid residues phenylalanine or tyrosine are to be replaced by a tryptophan and can help to predict the changes in the interactions. The observed results also show that DFT-D correctly describes the CH-π interaction energy and their additive properties in comparison to CCSD(T)/CBS calculated interaction energies. Thus, the DFT-D approach might be used for calculation of larger complexes of biological interest, where dispersion interaction plays an important role.


Docetaxel-loaded RIPL peptide (IPLVVPLRRRRRRRRC)-conjugated liposomes: Drug release, cytotoxicity, and antitumor efficacy.
We previously synthesized the RIPL peptide (IPLVVPLRRRRRRRRC) to facilitate selective delivery into hepsin-expressing cancer cells and showed that RIPL peptide-conjugated liposomes (RIPL-L) enhanced the intracellular delivery of fluorescent probes in vitro. In this study, docetaxel-loaded RIPL-L (DTX-RIPL-L) were prepared and evaluated for in vitro drug release, cytotoxicity, and in vivo antitumor efficacy. DTX was successfully encapsulated by pre-loading, with an average encapsulation efficiency and drug loading capacity of 32.4% and 21.39±2.05 (μg/mg), respectively. A DTX release study using dialysis showed a biphasic release pattern, i.e., rapid release for 6h, followed by sustained release up to 72h. The first-order equation provided the best fit for drug release (r2=0.9349). In vitro cytotoxicity was dose-dependent, resulting in IC50 values of 36.10 (SK-OV-3) and 48.62ng/mL (MCF-7) for hepsin-positive, and 61.12 (DU145) and 53.04ng/mL (PC-3) for hepsin-negative cell lines. Live/dead cell imaging was carried out to visualize the proportion of viable and nonviable SK-OV-3 cells. Compared to DTX solution, DTX-RIPL-L significantly inhibited tumor growth and prolonged survival time in BALB/c nude mice with SK-OV-3 cell tumors. We suggest that DTX-RIPL-L is a good candidate for efficient drug targeting to hepsin-expressing cancer cells.


Effects of T cell depletion in radiation bone marrow chimeras. I. Evidence for a donor cell population which increases allogeneic chimerism but which lacks the potential to produce GVHD.
The opposing problems of graft-vs-host disease (GVHD) and failure of alloengraftment present major obstacles to the application of bone marrow transplantation (BMT) across complete MHC barriers. The addition of syngeneic T-cell-depleted (TCD) bone marrow (BM) to untreated fully allogeneic marrow inocula in lethally irradiated mice has been previously shown to provide protection from GVHD. We have used this model to study the effects of allogeneic T cells on levels of chimerism in recipients of mixed marrow inocula. The results indicate that T cells in allogeneic BM inocula eliminate both coadministered recipient-strain and radioresistant host hematopoietic elements to produce complete allogeneic chimerism without clinical GVHD. To determine the role of GVH reactivity in this phenomenon, we performed similar studies in an F1 into parent combination, in which the genetic potential for GVHD is lacking. The presence of T cells in F1 marrow inocula led to predominant repopulation with F1 lymphocytes in such chimeras, even when coadministered with TCD-recipient-strain BM. These results imply that the ability of allogeneic BM cells removed by T cell depletion to increase levels of allochimerism may be mediated by a population which is distinct from that which produces GVHD. These results may have implications for clinical BM transplantation.


Endocrine regulation of airway clearance in Drosophila.
Fluid clearance from the respiratory system during developmental transitions is critically important for achieving optimal gas exchange in animals. During insect development from embryo to adult, airway clearance occurs episodically each time the molt is completed by performance of the ecdysis sequence, coordinated by a peptide-signaling cascade initiated by ecdysis-triggering hormone (ETH). We find that the neuropeptide Kinin (also known as Drosokinin or Leukokinin) is required for normal respiratory fluid clearance or "tracheal air-filling" in Drosophila larvae. Disruption of Kinin signaling leads to defective air-filling during all larval stages. Such defects are observed upon ablation or electrical silencing of Kinin neurons, as well as RNA silencing of the Kinin gene or the ETH receptor in Kinin neurons, indicating that ETH targets Kinin neurons to promote tracheal air-filling. A Kinin receptor mutant fly line (Lkrf02594 ) also exhibits tracheal air-filling defects in all larval stages. Targeted Kinin receptor silencing in tracheal epithelial cells using breathless or pickpocket (ppk) drivers compromises tracheal air-filling. On the other hand, promotion of Kinin signaling in vivo through peptide injection or Kinin neuron activation through Drosophila TrpA1 (dTrpA1) expression induces premature tracheal collapse and air-filling. Moreover, direct exposure of tracheal epithelial cells in vitro to Kinin leads to calcium mobilization in tracheal epithelial cells. Our findings strongly implicate the neuropeptide Kinin as an important regulator of airway clearance via intracellular calcium mobilization in tracheal epithelial cells of Drosophila.


Controlling the Self-Assembly Behavior of Aqueous Chitin Nanocrystal Suspensions.
As with many other biosourced colloids, chitin nanocrystals (ChNCs) can form liquid crystalline phases with chiral nematic ordering. In this work, we demonstrate that it is possible to finely tune the liquid crystalline behavior of aqueous ChNC suspensions finely. Such control was made possible by carefully studying how the hydrolysis conditions and suspension treatments affect the colloidal and self-assembly properties of ChNCs. Specifically, we systematically investigated the effects of duration and acidity of chitin hydrolysis required to extract ChNCs, as well as the effects of the tip sonication energy input, degree of acetylation, pH and ionic strength. Finally, we show that by controlled water evaporation, it is possible to retain and control the helicoidal ordering in dry films, leading to a hierarchical architecture analogous to that found in nature, e.g. in crab shells. We believe that this work serves as a comprehensive insight into ChNC preparation and handling which is required to unlock the full potential of this material in both a scientific and industrial context.


Patients' preference for radiotherapy fractionation schedule in the palliation of symptomatic unresectable lung cancer.
The palliative radiotherapeutic management of unresectable non-small-cell lung cancer is controversial, with various fractionation (Fx) schedules available. We aimed to determine patient's choice of Fx schedule after involvement in a decision-making process using a decision board. A decision board outlining the various advantages and disadvantages apparent in the Medical Research Council study of Fx schedules (17 Gy in two fractions vs 39 Gy in 13 fractions) was discussed with patients who met Medical Research Council eligibility criteria. Patients were then asked to indicate their preferred Fx schedules, reasons and their level of satisfaction with being involved in the decision-making process. Radiation oncologists (RO) could prescribe radiotherapy schedules irrespective of patients' preferences. Of 92 patients enrolled, 55% chose the longer schedule. English-speaking patients were significantly more likely to choose the longer schedule (P = 0.02, 95% confidence interval: 1.2-7.6). Longer Fx was chosen because of longer survival (90%) and better local control (12%). Shorter Fx was chosen for shorter overall treatment duration (80%), cost (61%) and better symptom control (20%). In all, 56% of patients choosing the shorter schedule had their treatment altered by the treating RO, whereas only 4% of patients choosing longer Fx had their treatment altered (P < 0.001). Despite this, all (100%) patients were satisfied with being involved in the decision-making process. The decision board was useful in aiding decision-making, with both Fx schedules being acceptable to patients. Interestingly, despite the longer average survival associated with longer Fx, nearly half of the patients believed that this was not as important as a shorter duration of treatment and lower cost. Despite patients' preferences, there were significant alterations of preferred schedules because of RO's own biases.


Good news, bad news: An analysis of 11,294 gunshot wounds (GSWs) over two decades in a single center.
Gun violence is a substantial public health problem accounting for significant physical, psychological, and financial costs. Although aggregate data sources demonstrate decreasing rates of firearm violence, analyses from individual trauma centers have shown that mortality and injury severity from gunshot wounds (GSWs) are increasing. To evaluate the evolving characteristics of gun violence in our region, we studied all GSWs admitted to our trauma center over a 20-year period. A retrospective analysis of all newly admitted patients with GSWs was performed from 1996 to 2016. Our trauma registry was used to collect data on demographics, mortality, injury severity, body regions injured, and geographic location of injury. Homicide data were obtained from local law enforcement. A total of 11,294 patients with GSWs were reviewed. The number of GSWs treated per biennium increased from 1,349 in 1996-1997 to 1,484 in 2014-2015, with a 59% increase occurring from 2010-2011 to 2014-2015. Overall mortality was 14.6% and decreased from 15.8% in 1996-1997 to 10.2% in 2014-2015 (p < 0.0001). Mean Injury Severity Score was 12.6 and the percentage of patients who suffered GSWs to ≥3 Abbreviated Injury Scale body regions increased from 2.5% in 1996-1997 to 7.7% in 2014-2015 (p < 0.0001). Local firearm homicide data show a 118% increase from 2010 to 2016. In contrast to other recent studies, we found that mortality decreased whereas the number of patients treated for GSWs and those with multicompartmental injuries increased. The decrease in mortality suggests improved trauma systems as well as an increase in nonfatal GSWs that dilutes overall mortality. Wounding in multiple body regions suggests more effective weaponry, including increased magazine size. The recent increase in local homicides parallels trends in registry data and illustrates worsening gun violence in our region. Further research is needed to understand local and regional determinants of increased gun violence to better guide prevention strategies. Epidemiological study, level III.


No difference in the long term final functional outcome after nailing or cast bracing of high energy displaced tibial shaft fractures.
Cast bracing (CB) has been a well established method of treating tibial shaft fractures. Majority of the recent literature on treatment of tibial shaft fractures have upheld intramedullary nailing (IMN) as the treatment of choice. Most of these studies are from the west, in public funded health set ups and in hospitals with very low rates of infection. This has lead to bewilderment in the minds of surgeons wishing to opt for conservative treatment in countries with scarcity of health resources. We therefore undertook this study to compare the two modalities in the scenario of the developing world. Sixty-eight consecutive patients were treated alternately with CB and IMN for high energy, displaced, closed and Gustilo Grade 1 open fractures of the tibial shaft, between 1995 and 2001. An average follow up at 4.3 years revealed no statistical difference in the final functional outcome as per Johner and Wruhs' criteria with modification to Indian lifestyle. IMN group had a) slightly shorter time to fracture union (mean 21.3 weeks versus 23.1 weeks for CB, p > 0.05), (b) lesser time off work (mean 17.6 weeks versus 25.6 weeks for CB, p <0.01), (c) fewer outpatient visits (mean 6.2 versus 9.7 for CB, p < 0.05), (d) less limb length discrepancy (mean 4.3 mm versus 6.6 mm for CB, p < 0.05). The difference in residual antero-posterior angulation (mean 3.2 degrees for IMN versus 4.9 degrees for CB, p = 0.14) and varus-valgus angulation (mean 3.7 degrees for IMN versus 5.1 degrees for CB, p = 0.7) were not statistically significant. However CB group had no deep infections as compared to two in the IMN group. The average cost of hospital treatment of CB group was less than half incurred by the IMN group (average USD 831 versus USD 2071 for nailed group, p < 0.05). Treating tibial shaft fracture either with IMN or CB provided equally gratifying results with no statistical difference in final functional outcome. The economic cost to the patient in Indian conditions is significantly less with CB and therefore stands as an equally reliable treatment option, especially in countries with fewer resources.


Influencing factors and hemodynamic study of initial and sustained orthostatic hypotension in middle-aged and elderly patients.
Orthostatic hypotension (OH) is a common autonomic disorder. This study aimed to investigate the influencing factors and hemodynamic mechanisms of initial and sustained OH in middle-aged and elderly patients. The authors analyzed the clinical characteristics and hemodynamic variables of patients aged ≥ 50 years according to the various forms of OH, diagnosed by an active orthostatic test using the CNAP monitor. The study included 473 participants; 119 (25.2%) patients had initial (54, 45.4%) or sustained (65, 54.6%) OH. Age, comorbidities, or medications did not differ significantly between the initial OH and non-OH groups. Sustained OH was associated with age and diabetes (p = .003 and p = .015, respectively). Hemodynamic analysis revealed higher cardiac output (CO) in the sustained OH group within 15 s than in the non-OH and initial OH groups (both p < .001); no difference in CO was observed between the initial OH and non-OH groups. The systemic vascular resistance (SVR) in both initial OH and sustained OH groups within 15 s was lower than that in the non-OH group (both p < .001). No differences in SVR at 3 min were observed between the initial OH and non-OH groups. The SVR at 3 min in the sustained OH group was significantly lower than in non-OH and initial OH groups (both p < .001). Age and diabetes emerged as the independent risk factors associated with sustained OH. Initial OH is associated with a mismatch of increase in CO and decrease in SVR. Sustained OH is mainly associated with sustained inadequate adjustment in SVR.


Intravitreal bevacizumab for iris neovascularization following proton beam irradiation for choroidal melanoma.
To evaluate the safety and efficacy of intravitreal injections of bevacizumab as an eye-sparing treatment for iris neovascularization (NVI) following proton beam irradiation for choroidal melanoma. Retrospective interventional case series. Four patients who received intravitreal bevacizumab for NVI following proton beam irradiation for choroidal melanoma were identified in the Department of Ophthalmology archives at the University of British Columbia. Clinical details were reviewed. Long-term follow-up of more than 2 years was detailed for each case. All 4 patients responded to a single injection of bevacizumab with regression of NVI. Neovascular glaucoma (NVG) was evident in 3 cases, 2 of which had stable intraocular pressure following treatment. NVI recurred following a single injection in all patients after an interval ranging from 1 month to 12 months. A longer period of regression was seen in patients with fewer systemic neovascular risk factors and earlier treatment. Regression of NVI following proton beam irradiation for choroidal melanoma was seen in all treated patients. Repeated treatments may be required to maintain regression of new vessels. This treatment modality may be a useful eye-sparing adjunct in the prevention and treatment of NVG following proton beam irradiation.


Using an incremental mean first passage approach to explore the viscosity dependent dynamics of the unbiased translocation of a polymer through a nanopore.
Noting the limitations of the standard characterization of translocation dynamics, an incremental mean first passage process methodology is used to more completely map the unbiased translocation of a polymer through a nanopore. In this approach, the average time t(0) required to reach successively increasing displacements for the first time is recorded - a measure shown to be more commensurate with the mean first passage nature of translocation. Applying this methodology to the results of Langevin dynamics simulations performed in three dimensions across a range of viscosities, a rich set of dynamics spanning regular diffusion at low viscosities to sub-diffusion at higher viscosities is revealed. Further, while the scaling of the net translocation time τ with polymer length N is shown to be viscosity-dependent, common regimes are found across all viscosities: super-diffusive behaviour at short times, an N-independent backbone consistent with τ ∼ N(2.0) at low viscosities and τ ∼ N(2.2) at higher viscosities for intermediate times, and N-dependent deviations from the backbone near the completion of translocation.


Pediatric office procedures.
The practice of pediatric urology has changed much during the last 25 years. Procedures that were once done only on inpatients are now done as ambulatory cases, comprising more than 60 per cent of all surgery. This trend has continued, with even more cases being done as office procedures. These consist of circumcision, meatotomy for stenosis, lysis of labial adhesions, and meatal dilatation after hypospadias repair. If an operation is done with attention to detail, it can be completed with minimal complications, although, as evidenced with circumcision, those that do occur can carry significant morbidity and even cause death. The primary limiting factor for performing procedures in the office is the comfort of the patient. The procedure, by necessity, has to entail minimum pain and great ease in obtaining hemostasis and requires a cooperative patient and family. Therefore, even as the number of operations performed on an out-patient basis increases, there are a finite number of cases suitable for the office.