High-Voltage, Multiphasic, Nanosecond Pulses to Modulate Cellular Responses.
Nanosecond electric pulses are an effective power source in plasma medicine and biological stimulation, in which biophysical responses are governed by peak power and not energy. While uniphasic nanosecond pulse generators are widely available, the recent discovery that biological effects can be uniquely modulated by reversing the polarity of nanosecond duration pulses calls for the development of a multimodal pulse generator. This paper describes a method to generate nanosecond multiphasic pulses for biomedical use, and specifically demonstrates its ability to cancel or enhance cell swelling and blebbing. The generator consists of a series of the fundamental module, which includes a capacitor and a MOSFET switch. A positive or a negative phase pulse module can be produced based on how the switch is connected. Stacking the modules in series can increase the voltage up to 5 kV. Multiple stacks in parallel can create multiphase outputs. As each stack is independently controlled and charged, multiphasic pulses can be created to produce flexible and versatile pulse waveforms. The circuit topology can be used for high-frequency uniphasic or biphasic nanosecond burst pulse production, creating numerous opportunities for the generator in electroporation applications, tissue ablation, wound healing, and nonthermal plasma generation.


Stability of the medial olivocochlear reflex as measured by distortion product otoacoustic emissions.
The purpose of this study was to assess the repeatability of a fine-resolution, distortion product otoacoustic emission (DPOAE)-based assay of the medial olivocochlear (MOC) reflex in normal-hearing adults. Data were collected during 36 test sessions from 4 normal-hearing adults to assess short-term stability and 5 normal-hearing adults to assess long-term stability. DPOAE level and phase measurements were recorded with and without contralateral acoustic stimulation. MOC reflex indices were computed by (a) noting contralateral acoustic stimulation-induced changes in DPOAE level (both absolute and normalized) at fine-structure peaks, (b) recording the effect as a vector difference, and (c) separating DPOAE components and considering a component-specific metric. Analyses indicated good repeatability of all indices of the MOC reflex in most frequency ranges. Short- and long-term repeatability were generally comparable. Indices normalized to a subject's own baseline fared best, showing strong short- and long-term stability across all frequency intervals. These results suggest that fine-resolution DPOAE-based measures of the MOC reflex measured at strategic frequencies are stable, and natural variance from day-to-day or week-to-week durations is small enough to detect between-group differences and possibly to monitor intervention-related success. However, this is an empirical question that must be directly tested to confirm its utility.


Cost of treating diabetic foot ulcers in five different countries.
Most estimates in the literature for the economic cost of treating a diabetic foot ulcer (DFU) are from industrialized countries. There is also marked heterogeneity between the complexity of cases considered in the different studies. The goal of the present article was to estimate treatment costs and costs to patients in five different countries (Chile, China, India, Tanzania, and the United States) for two hypothetical, but well-defined, DFUs at the extreme ends of the complexity spectrum. A co-author, who is a treating physician in the relevant country, was asked to choose treatment plans that represented the typical application of local resources to the DFU. The outcomes were pre-defined as complete healing in case 1 and trans-tibial amputation in case 2, but the time course of treatment was determined by each investigator in a manner that would be typical for their clinic. The costs, in local currencies, for each course of treatment were estimated with the assistance of local hospital administrators. Typical reimbursement scenarios in each country were used to estimate the cost burden to the patient, which was then expressed as a percentage of the annual per capita purchasing power parity-adjusted gross domestic product. There were marked differences in the treatment plans between countries based on the availability of resources and the realities of local conditions. The costs of treatment for case 1 ranged from Int$102 to Int$3959 in Tanzania and in the United States, respectively. The cost for case 2 ranged from Int$3060 to Int$188,645 in Tanzania and in the United States, respectively. The cost burden to the patient varied from the equivalent of 6 days of average income in the United States for case 1 to 5.7 years of average annual income for case 2 in India. Although these findings do not take cost-effectiveness into account, they highlight the dramatic economic burden of a DFU for patients in some countries.


Polydopamine-Derivated Hierarchical Nanoplatforms for Efficient Dual-Modal Imaging-Guided Combination in Vivo Cancer Therapy.
Exploring multifunctional nanomaterials from biocompatible constituents, with integrated imaging and targeted combination therapeutic modalities of tumors in vivo, provides great prospects for clinical cancer theranostic applications. Here, we report a combination strategy for functionalization of polydopamine (PDA) nanohosts with magnetic response and stimuli-controlled drug release capabilities for in vivo cancer theranostic. The high processability of PDA as nanotemplates and surface coating layers as well as its natural affinity to metals facilitated the sandwich of a compact iron oxide nanoparticle layer into the PDA matrix, realizing enhanced near-infrared (NIR) photothermal conversion and strong superparamagnetic responsiveness. Additionally, the high reactivity of the PDA surface allowed facile linkage with reduction-responsive prodrugs and polyethylene glycol chains for in vivo chemotherapy of cancer. Under the magnetic resonance imaging/photoacoustic imaging dual-modal tumor imaging and active magnetic tumor targeting of the nanoagents in vivo, the effective tumor eradication was achieved via synergetic NIR photothermal ablation and anticancer drug delivery.


International sepsis trial (INTERSEPT): role and impact of a clinical evaluation committee.
Several large clinical trials have recently evaluated a variety of potential therapeutic interventions for sepsis and have yielded negative results based on analyses of intention-to-treat cohorts. The present study was undertaken to evaluate the importance of a Clinical Evaluation Committee. Prospective, double-blind evaluation of a prospective, controlled, double-blind, randomized, multinational trial. Forty medical centers. Five hundred fifty-three infused patients with severe sepsis and septic shock. As part of an international trial (INTERSEPT) of antitumor necrosis factor therapy, a Scientific Extramural Review Committee prospectively defined and excluded patients with confounding events that objectively interfered with the potential of any intervention for sepsis to exercise its therapeutic effect. These confounding events included inappropriate antimicrobial therapy, inadequate medical-surgical management, underlying disorders, and forgoing life-sustaining therapies before management had failed. Patients who met all inclusion and exclusion criteria and who had no confounding events were defined as the Scientific Extramural Review Committee group. Five hundred fifty-three patients were enrolled in INTERSEPT. Seventy-seven patients did not meet inclusion and exclusion criteria. Sixty patients had confounding events, including inappropriate antimicrobial therapy (n = 28), inadequate medical-surgical management (n = 16), underlying disorders (n = 17), and forgoing life-sustaining therapies (n = 7). Four hundred sixteen patients were in the Scientific Extramural Review Committee group and their mortality rates were different from the mortality rates of the intent-to-treat cohort. In the intent-to-treat analysis among shock patients, low-dose anti-tumor necrosis factor reduced 28-day mortality by 14.5% (p = .34), whereas in the Scientific Extramural Review Committee group, the study drug reduced mortality by 26.5% (p = .16). More patients in the high dose anti-tumor necrosis factor treatment arm (31/176) were in the invalid Scientific Extramural Review Committee group than in the other two arms (16/157 and 13/143, respectively, p < .05). In large trials of sepsis, in addition to analyzing the intent-to-treat cohort, patients in compliance with the protocol and with no confounding events should also be analyzed. These results should assist in determining whether treatment groups are comparable and provide a greater likelihood of demonstrating the potential efficacy of a new therapy for sepsis. A Clinical Evaluation Committee is important to properly assess a clinical sepsis trial.


Tensor fascia lata myocutaneous flap in lower abdominal wall reconstruction.
The tensor fascia lata myocutaneous flap provides a reliable autogenous building block for anatomical lower abdominal wall reconstruction. Preservation of innervation allows maintenance of voluntary motor control and protective sensation. The excellent blood supply of this flap is particularly helpful in reconstructing previously irradiated areas. A one-stage repair is possible, leaving minimal secondary defect. We describe 4 patients illustrating the uses and versatilty of this flap. Anatomy, operative procedures, and indications for delay are also discussed.


An orbital-invariant and strictly size extensive post-Hartree-Fock correlation functional.
A strictly size extensive post-Hartree-Fock correlation functional being invariant with respect to orbital transformations within the occupied and virtual subspaces is presented. While avoiding the necessity to solve additional Z vector equations for the calculation of properties and energy gradients, this functional reproduces almost exactly the results of coupled-cluster singles doubles (CCSD) calculations. In particular, it is demonstrated that the method is rigorous in the sense that it can be systematically improved by the perturbative inclusion of triple excitations in the same way as CCSD. As to the computational cost, the presented approach is somewhat more expensive than the CCSD if the energy is variationally optimized with respect to both the orbitals and the excitation amplitudes. Replacement of orbital optimization by the Brueckner condition reduces the computational cost by a factor of two, thus making the method less expensive than CCSD.


Monte Carlo simulation of a prototypical patient dosimetry system for fluoroscopic procedures.
The purpose of this study is to investigate feasibility of a novel real-time dosimetry method for fluoroscopically guided interventions utilizing thin-film detector arrays in several potential locations with respect to the patient and x-ray equipment. We employed Monte Carlo (MC) simulation to establish the fluoroscopic beam model to determine dosimetric quantities directly from measured doses in thin-film detector arrays at three positions: A-attached to the x-ray source, B-on the couch under the patient and C-attached to the fluoroscopic imager. Next, we developed a calibration method to determine skin dose at the entry of the beam ([Formula: see text]) as well as the dose distribution along each ray of the beam in a water-equivalent patient model. We utilized the concept of water-equivalent thickness to determine the dose inside the patient based on doses measured outside of the patient by the thin-film detector array layers: (a) A, (b) B, or (c) B and C. In the process of calibration we determined a correction factor that characterizes the material-specific response of the detector, backscatter factor and attenuation factor for slab water phantoms of various thicknesses. Application of this method to an anthropomorphic phantom showed accuracy of about 1% for [Formula: see text] and up to about 10% for integral dose along the beam path when compared to a direct simulation of dose by MC.


Simultaneous PET and MR imaging.
We have developed a prototype PET detector which is compatible with a clinical MRI system to provide simultaneous PET and MR imaging. This single-slice PET system consists of 48 2 x 2 x 10 mm3 LSO crystals in a 38 mm diameter ring configuration that can be placed inside the receiver coil of the MRI system, coupled to three multi-channel photomultipliers housed outside the main magnetic field via 4 m long and 2 mm diameter optical fibres. The PET system exhibits 2 mm spatial resolution, 41% energy resolution at 511 keV and 20 ns timing resolution. Simultaneous PET and MR phantom images were successfully acquired.


Regional variations of contractile activity in isolated rat lymphatics.
To evaluate lymphatic contractile activity in different regions of the lymphatic system in a single animal model (the rat thoracic duct, mesenteric, cervical, and femoral lymphatics) in response to changes in lymph pressure and flow. The systolic and diastolic diameters of isolated, cannulated, and pressurized lymphatic vessels were measured. Contraction frequency, ejection fraction, and fractional pump flow were determined. The influences of incrementally increased transmural pressure (from 1 to 9 cm H2O) and imposed flow (from 1 to 5 cm H2O transaxial pressure gradient) were investigated. The authors determined regional differences in lymphatic contractility in response to pressure and imposed flow. They found the highest pumping (at the optimal pressure levels) in mesenteric lymphatics and lowest pumping in thoracic duct. All lymphatics had their optimal pumping conditions at low levels of transmural pressure. Different degrees of the flow-induced inhibition of the pump were observed in the different types of lymphatics. During high flow, the active lymph pumps in thoracic duct and cervical lymphatics were almost completely abolished, whereas mesenteric and femoral lymphatics still exhibited significant active pumping. The active lymph pumps in different regions of the rat body express variable relative strengths and sensitivities that are predetermined by different hydrodynamic factors and regional outflow resistances in their respective locations.


Preoperative N staging of gastric cancer by stomach protocol computed tomography.
Clinical stage of gastric cancer is currently assessed by computed tomography. Accurate clinical staging is important for the tailoring of therapy. This study evaluated the accuracy of clinical N staging using stomach protocol computed tomography. Between March 2004 and November 2012, 171 patients with gastric cancer underwent preoperative stomach protocol computed tomography (Jeju National University Hospital; Jeju, Korea). Their demographic and clinical characteristics were reviewed retrospectively. Two radiologists evaluated cN staging using axial and coronal computed tomography images, and cN stage was matched with pathologic results. The diagnostic accuracy of stomach protocol computed tomography for clinical N staging and clinical characteristics associated with diagnostic accuracy were evaluated. The overall accuracy of stomach protocol computed tomography for cN staging was 63.2%. Computed tomography images of slice thickness 3.0 mm had a sensitivity of 60.0%; a specificity of 89.6%; an accuracy of 78.4%; and a positive predictive value of 78.0% in detecting lymph node metastases. Underestimation of cN stage was associated with larger tumor size (P<0.001), undifferentiated type (P=0.003), diffuse type (P=0.020), more advanced pathologic stage (P<0.001), and larger numbers of harvested and metastatic lymph nodes (P<0.001 each). Tumor differentiation was an independent factor affecting underestimation by computed tomography (P=0.045). Computed tomography with a size criterion of 8 mm is highly specific but relatively insensitive in detecting nodal metastases. Physicians should keep in mind that computed tomography may not be an appropriate tool to detect nodal metastases for choosing appropriate treatment.


The complete mitochondrial genome of Lithobates catesbeianus (Anura: Ranidae).
The complete mitochondrial genome of Lithobates catesbeianus (Anura: Ranidae) is sequenced to analyze the gene arrangement. It is a circular molecule of 18,241 bp in length including 37 genes typically found in other frogs. The AT content of the overall base composition of L. catesbeianus is 59.9%. The length of control region is 2783 bp with 66.0% AT content. Protein-coding genes begin with ATG as start codon except except ND1 and ATP6 began with ATA, COI and ND4L with GTG, and ND2 with ATT. COI end with AGG as stop codon, COII and ND6 end with AGA, ND2 end with TAG, ATP8. ND4L. ND5 and Cytb end with TAA, and the other five PCGs end with a incomplete stop codon (a single stop nucleotide T).


Compartmentation in Vicia faba Leaves: II. Kinetics of C-Sucrose Redistribution among Individual Tissues following Pulse Labeling.
Leaflets of Vicia faba L. were pulse labeled with (14)CO(2) and the kinetics of (14)C-sucrose redistribution among individual tissues was followed. Sucrose specific activity in the whole leaf peaked about 15 minutes after labeling and declined with a half-time of about 80 minutes. In one experiment, leaflet discs taken at various times during the (12)CO(2) chase were quick frozen, freeze-substituted, and embedded in plastic. The tissue was sectioned paradermally and sections of palisade parenchyma, of spongy parenchyma, and of spongy parenchyma that contained veins were collected. Water extracts from these sections were assayed for sucrose specific activity. Sucrose specific activity in the palisade parenchyma was higher than that of the spongy parenchyma and reached a maximum in both tissues 9 to 15 minutes after labeling. Sucrose specific activity initially declined rapidly in the palisade parenchyma followed by a period during which little or no loss occurred. Sucrose specific activity in sections containing veins peaked at 15 minutes with a maximum value substantially higher than either mesophyll tissue, indicating that recently synthesized sucrose was preferentially exported from the mesophyll. Decline of activity in these sections containing veins continued for the remainder of the experiment. Sucrose specific activity in lower epidermal peels peaked several minutes after that of the whole leaflet and remained lower. Sucrose specific activity in upper epidermal peels was variable (probably due to contamination), but the limited data suggest that the sucrose specific activity there reached somewhat higher values than those of the lower epidermis. The experiments indicate that each leaf tissue contains a kinetically identifiable sucrose pool (which we refer to as "histological compartmentation"), and that further compartmentation may occur at the intracellular level. A simulation of leaf sucrose compartmentation is presented.


ab initio Energetics and Thermoelectric Profiles of Gallium Pnictide Polytypes.
The state-of-the-art Density Functional Theory (DFT) is utilized to investigate the structural, electronic, vibrational, thermal and thermoelectric properties of gallium pnictides GaX (X = P, As, Sb) in cubic zincblende (ZB) and hexagonal wurtzite (WZ) phases. The lattice parameters, bulk modulus, energy band nature and bandgap values, phonon, thermal and thermoelectric properties are revisited for ZB phase while for WZ phase they are predictive. Our results agree reasonably well with the experimental and theoretical data wherever they are available. The phonon dispersion curves are computed to validate the dynamic stability of these two polytypes and for further investigating the thermal and thermoelectric properties. Our computed thermoelectric figure of merit ZT gives consistent results with highest observed magnitude of 0.72 and 0.56 for GaSb compound in ZB and WZ phases respectively. The first time calculated temperature variation of lattice thermal conductivity for WZ phase shows lower value than ZB phase and hence an important factor to enhance the figure of merit of considered gallium pnictides in WZ phase. Present results validate the importance of GaX in high temperature thermoelectric applications as the figure of merit ZT shows enhancement with significant reduction in thermal conductivity at higher temperature values.


Strictureplasty in Crohn's disease: short- and long-term follow-up.
Strictureplasty for obstructive Crohn's disease is still controversial because lesions are left in place and the suture is performed on a diseased bowel. Many surgeons prefer to perform bowel resection, hoping for fewer complications and a lower recurrence rate. In this paper, the authors reports their strictureplasty experience. They performed a systematic retrospective review of the patients suffering from Crohn's disease who underwent strictureplasties during a 10-year period in the abdominal surgery department of the University Hospital of Liège Sart Tilman, and studied the short- and long-term clinical results of 68 strictureplasties performed in 18 patients. Median follow-up was 63 months (range 12 to 144). Mortality was 0% and septic morbidity was 11% (one wound abscess and one leakage). Among the 16 patients available for the latest follow-up, symptomatic stenotic recurrence had to be medically treated in hospital for 4 patients (25%) with a recurrence delay range of 19 to 49 months. Stenosis recurrence needed re-intervention in one patient 48 months after surgery: stenosis occurred at a distance from the corrected site. These results confirmed that strictureplasty is a safe and efficient procedure in selected patients undergoing surgery for obstructive Crohn's disease.


Worry and Permissive Parenting in Association with the Development of Internet Addiction in Children.
The Internet has experienced a rapid increase in use globally. Specifically, more than 90% of Hong Kong's citizens use the Internet, and 70% of children in the age group of 6-17 years have daily access to it. However, internet addiction could pose serious social and health issues. Therefore, conducting research to investigate its causes and risk factors is fundamental. The current study examined the relationship between worry and Internet addiction among children in Hong Kong and investigated the moderating effect of the permissive parenting style on such a relationship. The participants consisted of 227 fourth- and fifth-grade students (120 males, 52.9%) with a mean age of 9.55 (standard deviation (SD) = 0.58) in Hong Kong. Each participant was asked to complete the questionnaires, including the Internet Addiction Test for Internet addiction, the Penn State Worry Questionnaire for Children for worry, and the Parental Authority Questionnaire for the permissive parenting style. The results indicated that worry was related to greater Internet addiction among children. Furthermore, there was a moderating effect of the permissive parenting style such that the positive association between worry and Internet addiction was stronger when the permissive parenting style was higher. Our findings imply that parenting styles are influential in the prevention of Internet addiction.


FUSARIUM SOLANI SUBRETINAL ABSCESS IN A PATIENT WITH ACUTE MYELOID LEUKEMIA.
To report on a case of Fusarium solani subretinal abscess in a patient with acute myeloid leukemia treated with an allogenic bone marrow transplant. A 47-year-old male with a history of acute myeloid leukemia with intermediate cytogenetic risk was admitted in our hospital. The disease relapsed after two cycles of chemotherapy. He was then treated with an allogenic bone marrow transplant, with busulfan, cyclophosphamide, and thymoglobulin. One week after the procedure, a sepsis of unknown origin in neutropenia occurred. Blood cultures and sputum were negative for bacteria and fungi. At the eighth week after the procedure, the patient had acute vision loss of the right eye. Funduscopy in the right eye revealed an inferior temporal yellowish white elevated lesion of approximately 10 disk areas and superficial perifoveal and perilesional hemorrhages. Vitrectomy was performed and samples from the vitreous and the subretinal abscess material were sent for analysis. Vitreous and subretinal specimens grew colonies of a fungus morphologically consistent with F. solani. Fusarium solani should be included in the differential diagnosis of subretinal abscesses.


On hepatocellular carcinoma in South America and early-age onset of the disease.
Hepatocellular carcinoma (HCC) is one of the most predominant tumor types worldwide, being particularly prevalent in sub-Saharan Africa and East Asia. However, HCC is inexplicably underreported in South America, despite unsettling clinical epidemiological trends of the disease on this continent. Here, we review the current knowledge on HCC presentation in Peru. We emphasize the well-documented occurrence of an early-age nosological form of the disease in Andean descent populations. We further discuss the reasons for such HCC clinical presentation, as well as the implications for liver cancer screening, management, and prevention.


Dopamine differentially modulates the excitability of striatal neurons of the direct and indirect pathways in lamprey.
The functions of the basal ganglia are critically dependent on dopamine. In mammals, dopamine differentially modulates the excitability of the direct and indirect striatal projection neurons, and these populations selectively express dopamine D1 and D2 receptors, respectively. Although the detailed organization of the basal ganglia is conserved throughout the vertebrate phylum, it was unknown whether the differential dopamine modulation of the direct and indirect pathways is present in non-mammalian species. We aim here to determine whether the receptor expression and opposing dopaminergic modulation of the direct and indirect pathways is present in one of the phylogenetically oldest vertebrates, the river lamprey. Using in situ hybridization and patch-clamp recordings, we show that D1 receptors are almost exclusively expressed in the striatal neurons projecting directly to the homolog of the substantia nigra pars reticulata. In addition, the majority of striatal neurons projecting to the homolog of the globus pallidus interna/globus pallidus externa express D1 or D2 receptors. As in mammals, application of dopamine receptor agonists differentially modulates the excitability of these neurons, increasing the excitability of the D1-expressing neurons and decreasing the excitability of D2-expressing neurons. Our results suggest that the segregated expression of the D1 and D2 receptors in the direct and indirect striatal projection neurons has been conserved across the vertebrate phylum. Because dopamine receptor agonists differentially modulate these pathways, increasing the excitability of the direct pathway and decreasing the excitability of the indirect pathway, this organization may be conserved as a mechanism that biases the networks toward action selection.


Racialization as a Barrier to Achieving Health Equity for Native Americans.
Racial identity is a complex idea, particularly for American Indian and Alaska Native (AI/AN) populations. The idea of a single AI/AN race developed from a European-American view of phenotypic and cultural differences. It continues to have significant consequences for AI/AN populations within the clinical-medical context. For clinicians, using this flawed category in medical decision making poses ethical challenges and has implications for patient autonomy and justice. This article briefly traces the development of the idea of an AI/AN race, the concerns raised in using this identity marker, and the ethical implications of employing the categorization.


Variables, Dimensions, and Indicators Important to Develop the Multidimensional Poverty Line Measurement in Indonesia.
Criticism on the use of the income/expenditure poverty line to estimate the number of the poor in Indonesia leads to questioning the use of the multidimensional poverty line (MPL) measurement. While current research on the defining variables, dimensions, and indicators to develop the MPL measurement in Indonesia was not based on direct views of the poor and the non-poor household heads, we complement this research gap by examining it based on direct views of the poor and the non-poor household heads. Methods used to collect the empirical data were conducted in four stages. The first stage was by organizing a Focus Group Discussion with twenty-five participants. The second stage was by conducting a pilot for the main survey on thirty poor and non-poor household heads. The third stage was by distributing the main survey questionnaire to 274 non-poor and 315 poor household head respondents in six representative locations in Indonesia. The fourth stage was by taking in-depth interviews with 8-12 key informants in each survey location. These data were further analysed by employing the qualitative technique. The results confirmed that the poor and the non-poor household head respondents, and the interviewees under the survey viewed the MPL measurement as a comprehensive and better poverty measurement. However, dimensions and indicators that were viewed to be important in developing the MPL measurement were mostly in the groups of three variables. These three variables were capability, empowerment, and opportunity. These three variables should be no hierarchy of importance in developing the MPL measurement as well as in formulating policy and programs to eradicate the incidence of poverty in Indonesia.


A meaningful relief from suffering experiences of massage in cancer care.
The experience of massage in an oncology ward was the focus of this study. Eight female cancer patients were given massage for 10 consecutive days and then interviewed using phenomenology as a theoretical framework. The essential meaning of getting massage as part of the daily care for female cancer patients was described as getting a meaningful relief from suffering. The findings identified five themes: the relief is meaningful because it offers the patient an experience of being "special." The massage contributes to the development of a positive relationship with the personnel, to feeling strong, and to a balance between autonomy and dependence. The massage also brings about a meaningful relief from suffering because it just "feels good." The findings of this study can be of use to health care professionals as it shows that the relatively short period of massage can result in physical and emotional benefits for cancer patients.


Antibacterial efficacy of silver nanoparticles and ethyl acetate's metabolites of the potent halophilic (marine) bacterium, Bacillus cereus A30 on multidrug resistant bacteria.
Bacteria are generally responsible for the prevalence of several diseases and pathogenic bacteria are showing increasing resistance to different antibacterials. During the present study an extremophilic bacterium-A30 isolated from the marine waters was characterized and evaluated against four multi-drug resistant (MDR) pathogens, viz; Methicillin-resistant Staphylococcus aureus (MRSA), Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa. The sensitivity pattern of the selected pathogens was tested with 31 antibiotics. Among the 47 marine microbial extracts tested on 4-MDR pathogens viz: Methicillin-resistant Staphylococcus aureus (MRSA), E. coli, K. pneumoniae and P. aeruginosa, only our strain A30 strain exhibited highest efficacy. This strain was subsequently subjected to 16S rDNA sequencing which confirmed its allocation as Bacillus cereus. Silver nanoparticle (AgNPs) synthesis and ethyl acetate extraction were performed using the supernatant of B. cereus. The synthesized AgNPs were characterized by UV-Visible, Fourier-transform infra-red (FT-IR), X-ray diffraction (XRD), Field emission-scanning electron microscopy (FE-SEM), energy dispersive X-ray spectroscopy (EDX), and Zeta potential analyses. The presence of functional groups and 13 bioactive components in the ethyl acetate extract were analyzed using FT-IR and gas chromatography-mass spectrometry (GC-MS). The synthesized of AgNPs and the ethyl acetate extract showed preponderant activity against P. aeruginosa and MRSA, respectively. The effects of AgNPs were significant when compared to ethyl acetate extract. Therefore, the halophilic bacterium, B. cereus mediated AgNPs could provide antibacterial applications in the biomedical industries.


Uncertainty evaluation in the measurement of power frequency electric and magnetic fields from AC overhead power lines.
Measurements of power frequency electric and magnetic fields from alternating current power lines are carried out in order to evaluate the exposure levels of the human body on the general public. For any electromagnetic field measurement, it is necessary to define the sources of measurement uncertainty and determine the total measurement uncertainty. This paper is concerned with the problems of measurement uncertainty estimation, as the measurement uncertainty budget calculation techniques recommended in standardising documents and research studies are barely described. In this work the total uncertainty of power frequency field measurements near power lines in various measurement sites is assessed by considering not only all available equipment data, but also contributions that depend on the measurement procedures, environmental conditions and characteristics of the field source, which are considered to increase the error of measurement. A detailed application example for power frequency field measurements is presented here by accredited laboratory.


Post-traumatic kyphosis. A review of forty-eight surgically treated patients.
We reviewed the cases of forty-eight patients who were treated surgically for symptomatic post-traumatic kyphosis of the thoracic or lumbar spine six months or longer after the initial injury. Presenting signs and symptoms included pain in 94 per cent, progression of kyphosis in 46 per cent, instability in 36 per cent, and increasing neural deficit in 27 per cent. Twenty-four patients had had a prior laminectomy. Posterior fusion (sixteen patients) and combined anterior and posterior fusion (twenty patients) always resulted in primary fusion. Anterior fusion alone was attempted in twelve patients, but failed in six. The average final correction of the deformity was 26 per cent. Pain was reduced significantly in 31 per cent of the patients and was relieved completely in 67 per cent. Fourteen of the forty-eight patients also had an anterior decompression, of whom five were neurologically improved, four were unchanged or stabilized, and four were immediately worse after operation. One patient was neurologically stable for twenty-three months postoperatively and then deteriorated again. No patients were neurologically improved following posterolateral decompression or repeat exploratory laminectomy.


Kondo effect in a quantum antidot.
We report Kondo-like behavior in a quantum antidot (a submicron depleted region in a two-dimensional electron gas) in the quantum-Hall regime. When both spins of the lowest Landau level are present all around the antidot, the resonances between extended edge states via antidot bound states show an abnormal feature in alternate Coulomb-blockaded regions. The feature becomes suppressed when the temperature or source-drain bias is raised as for Kondo resonances in quantum dots. Although the exact mechanism is unknown, Kondo-like correlated tunneling may arise from a Skyrmion-type edge reconstruction. This observation demonstrates the generality of the Kondo phenomenon.


The Iliac Crest Osteomuscular Flap for Bony Reconstruction: Beast or Beauty? A Reassessment of the Value and Donor Site Morbidity in the CAD/CAM Era.
The iliac crest bone flap (ICBF), based on the deep circumflex iliac artery, has a bad reputation regarding donor site morbidity. However, the ICBF has an ideal curvature and shape for occlusion-based hemimandibular reconstructions with rapid dental rehabilitation and for vertical class III maxillary reconstructions that require bony support and muscular bulk to fill cavities and to provide intraoral lining. Is this notorious donor site reputation still valid with modern flap procurement using computer aided design/computer aided manufacturing (CAD/CAM) and recipient-site closure techniques? We performed a literature search of the public databases PubMed, Cochrane, Google Scholar, and Web of Science for papers using mesh keywords related to donor site morbidity of the ICBF. We report three illustrative case reports using our current protocols for oncologic bony resection and reconstruction, using in-house CAD/CAM and three-dimensional printing to procure a tight-fit ICBF and minimizing donor site morbidity. We found 191 articles in the PubMed database of which we considered 176 nonrelevant. Cochrane Library and Google Scholar database searches resulted in the inclusion of 11 additional papers. The second search resulted in 172 articles of which we used five after excluding nonrelevant papers. Accurate preoperative (CAD/CAM) planning, preservation of the anterior superior iliac spine (ASIS), and paying attention to thoroughly donor site closure make the ICBF a very valuable option for accurate maxillofacial reconstructions with very acceptable comorbidities. This corresponds with our clinical findings. Dogma never is a good teacher; it remains elementary that routine "knowledge" is (re)questioned. Donor site morbidity of the ICBF is comparable to other bone flaps. The shape and bone stock of the ICBF is ideal and often may be first choice. In combination with CAD/CAM planning, the ICBF is an excellent option for specific maxillofacial reconstructions.


Progressive massive fibrosis in a zinc miner.
The diagnosis of progressive massive fibrosis (PMF) is traditionally associated with exposure to coal dust. Since the legislation of better control of mine dust, the incidence of PMF has declined significantly. Clinicians who are not regularly involved in the medical care of coal workers may have limited knowledge of this incapacitating problem. Physicians are reminded that PMF is a complex process that can occur after exposure to mixed respirable particles other than coal dust.


Applications of CRISPR-Cas Technologies to Proteomics.
CRISPR-Cas-based genome editing is a revolutionary approach that has provided an unprecedented investigational power for the life sciences. Rapid and efficient, CRISPR-Cas technologies facilitate the generation of complex biological models and at the same time provide the necessary methods required to study these models in depth. The field of proteomics has already significantly benefited from leveraging the power of CRISPR-Cas technologies, however, many potential applications of these technologies in the context of proteomics remain unexplored. In this review, we intend to provide an introduction to the CRISPR-Cas technologies and demonstrate how they can be applied to solving proteome-centric questions. To achieve this goal, we begin with the description of the modern suite of CRISPR-Cas-based tools, focusing on the more mature CRISPR-Cas9 system. In the second part of this review, we highlight both established and potential applications of the CRISPR-Cas technologies to proteomics.


Look who's talking: deregulated signaling in colorectal cancer.
The phenotypic expression of any given heterogeneous tissue type is the composite of interactions between individual cell types governed principally by inherent, cell-specific molecular mechanisms. Using a combination of laser-capture microdissection, oligonucleotide microarrays, bioinformatic and statistical tools, we analyzed colorectal cancer tissues in order to spot the significant pathways that were differentially deregulated between the epithelial and stromal compartments and compared these alongside the ones of whole tissue dissection. The stromal pathway profiles were very similar to the ones of whole tissue, in contrast to the epithelial input, with stroma emerging as the major determinant of the cancer phenotype. Differentially expressed genes in the epithelial compartment correlated significantly with the carbohydrate antigen 19-9 tumor marker. The accurate interpretation of data arising from the analysis of heterogeneous tissue structures lends itself to inherent biases of its constitutive components with each component presenting explorable analytical advantages.


Mesenchymal stem cell therapy for paraquat poisoning: A systematic review and meta-analysis of preclinical studies.
Paraquat (PQ) poisoning can cause multiple organ failure, in which the lung is the primary target organ. There is currently no treatment for PQ poisoning. Mesenchymal stem cells (MSCs), which differentiate into multiple cell types, have generated much enthusiasm regarding their use for the treatment of several diseases. The aim of this study was to systematically review and analyze published preclinical studies describing MSC administration for the treatment of PQ poisoning in animal models to provide a basis for cell therapy. The electronic databases PubMed and CBMdisc were searched in this systematic review and meta-analysis. The MSC treatment characteristics of animal models of PQ poisoning were summarized. After quality assessment was performed, the effects of MSC transplantation were evaluated based on the survival rate, lung wet/dry weight, fibrosis scores, oxidative stress response, and inflammatory response. Publication bias was assessed. Eleven controlled preclinical studies involving MSC transplantation in animal models of PQ poisoning were included in this review. MSC therapy improved the survival rate and reduced the lung wet/dry weight and histopathological fibrosis changes in most studies. MSCs decreased serum or plasma malondialdehyde levels in the acute phase after 7 and 14 d and increased serum or plasma superoxide dismutase and glutathione levels at the same time points. IL-1β, TNF-α and TGF-β1 levels in blood or lung tissues were decreased to different degrees by MSCs. Lung hydroxyproline was decreased by MSCs after 14 d. No obvious evidence of publication bias was found. MSCs showed anti-fibrosis therapeutic effects in animal models of lung injury caused by PQ poisoning, which may be related to reduced oxidative stress and inflammatory cytokine levels. Our review indicates a potential therapeutic role for MSC therapy to treat PQ poisoning and serves to augment the rationale for clinical studies.


The prognostic IDH1( R132 ) mutation is associated with reduced NADP+-dependent IDH activity in glioblastoma.
Somatic mutations in the isocitrate dehydrogenase 1 gene (IDH1) occur at high frequency in gliomas and seem to be a prognostic factor for survival in glioblastoma patients. In our set of 98 glioblastoma patients, IDH1 ( R132 ) mutations were associated with improved survival of 1 year on average, after correcting for age and other variables with Cox proportional hazards models. Patients with IDH1 mutations were on average 17 years younger than patients without mutation. Mutated IDH1 has a gain of function to produce 2-hydroxyglutarate by NADPH-dependent reduction of alpha-ketoglutarate, but it is unknown whether NADPH production in gliomas is affected by IDH1 mutations. We assessed the effect of IDH1 (R132 ) mutations on IDH-mediated NADPH production in glioblastomas in situ. Metabolic mapping and image analysis was applied to 51 glioblastoma samples of which 16 carried an IDH1 (R132 ) mutation. NADP+-dependent IDH activity was determined in comparison with activity of NAD+-dependent IDH and all other NADPH-producing dehydrogenases, glucose-6-phosphate dehydrogenase, 6-phosphogluconate dehydrogenase, malate dehydrogenase, and hexose-6-phosphate dehydrogenase. The occurrence of IDH1 mutations correlated with approx. twofold diminished NADP+-dependent IDH activity, whereas activity of NAD+-dependent IDH and the other NADP+-dependent dehydrogenases was not affected in situ in glioblastoma. The total NADPH production capacity in glioblastoma was provided for 65% by IDH activity and the occurrence of IDH1 (R132 ) mutation reduced this capacity by 38%. It is concluded that NADPH production is hampered in glioblastoma with IDH1 (R132 ) mutation. Moreover, mutated IDH1 consumes rather than produces NADPH, thus likely lowering NADPH levels even further. The low NADPH levels may sensitize glioblastoma to irradiation and chemotherapy, thus explaining the prolonged survival of patients with mutated glioblastoma.


Danio rerio Oocytes for Eukaryotic In-Cell NMR.
Understanding how the crowded and complex cellular milieu affects protein stability and dynamics has only recently become possible by using techniques such as in-cell nuclear magnetic resonance. However, the combination of stabilizing and destabilizing interactions makes simple predictions difficult. Here we show the potential of Danio rerio oocytes as an in-cell nuclear magnetic resonance model that can be widely used to measure protein stability and dynamics. We demonstrate that in eukaryotic oocytes, which are 3-6-fold less crowded than other cell types, attractive chemical interactions still dominate effects on protein stability and slow tumbling times, compared to the effects of dilute buffer.


Peer Tutoring Effects on Students' Mathematics Anxiety: A Middle School Experience.
In this research the effects of reciprocal peer tutoring on students' mathematics anxiety levels were examined. A pretest posttest with control group design was used at a public middle school in Spain. A total of 420 students in 7th, 8th, and 9th grades participated in the study, of which 215 were female and 205 were male. Students were randomly assigned and equally distributed by course grade (140 in each course grade) and experimental condition (210 in the experimental group and 210 in the control group). Quantitative data were gathered using the Mathematics Anxiety Scale developed by Chiu and Henry (1990). Qualitative information was gathered during eight focus group sessions that were held with students. Two main factors were analyzed using the quantitative and qualitative information: mathematics learning anxiety and mathematics evaluation anxiety. Results were analyzed by gender and course grade. Statistically significant improvements were reported for both male and female students in the experimental group and for each course grade for both factors. No statistically significant differences were reported for students in the control group in any case. A moderate effect size was reported for mathematics evaluation anxiety (Hedge's g = 0.42), and a large effect size was reported for mathematics learning anxiety (Hedge's g = 0.84). Information obtained from the focus groups was consistent with the reported quantitative results. The main conclusion is that peer tutoring may be very beneficial for reducing middle school students' mathematics anxiety, regardless of their gender or grade.


Is There an Age Cutoff for Intracranial Pressure Monitoring?: A Propensity Score Matched Analysis of the National Trauma Data Bank.
Despite mostly favorable past evidence for use of intracranial pressure monitoring (ICPM), more recent data question not only the indications but also the utility of ICPM. The Fourth Edition Brain Trauma Foundation guidelines offer limited indications for ICPM. Evidence supports ICPM for reducing mortality in patients with severe traumatic brain injury (TBI) and cites decreased survival in elderly patients. All patients ≥ 18 years of age with isolated TBI, head Abbreviated Injury Scale (AIS) ≥ 3, and a Glasgow Coma Scale (GCS) ≤ 8 between 2008 and 2014 were included from the National Trauma Data Bank. Exclusion criteria were head AIS = 6 and death within 24 hours. Patients with and without ICPM were compared using TBI-specific variables. Patients were then matched via propensity-score matching (PSM), and the odds ratio (OR) of death with ICPM was determined using logistic regression modeling for 8 different age strata. A total of 23,652 patients with a mean age of 56 years, median head AIS of 4, median GCS of 3, and overall mortality of 29.2% were analyzed. After PSM, ICPM was associated with death beginning at the age stratum of 56-65 years. Intracranial pressure monitoring was associated with survival beginning at the age-group 36-45 years. Based on a large propensity-matched sample of TBI patients, ICPM was not associated with improved survival for TBI patients above 55 years of age. Until level 1 evidence is available, this age threshold should be considered for further prospective study in determining indications for ICPM.


[A case of urachal abscess accompanied by a stone].
A 64-year-old woman presented to our hospital with the chief complaints of abdominal pain and appetite loss, and she was admitted to the internal medicine department. Kidney, ureter and bladder X-ray revealed intrapelvic calcification near the bladder, and so, the patient consulted our department. Computed tomography and magnetic resonance imaging revealed an urachal abscess accompanied by a stone. Open surgery was performed under general anesthesia. The mass adhered tightly to the intestine and bladder. The urachal abscess ruptured during the operation, and pus leaked into the intraabdominal cavity. Partial cystectomy was performed to remove the mass completely. The stone existed in the urachal abscess, and its constituents were CaOxa (51%) and CaP (49%). The pathological diagnosis was urachal abscess without malignancy.


Method for measuring violin sound radiation based on bowed glissandi and its application to sound synthesis.
This work presents a method for measuring and computing violin-body directional frequency responses, which are used for violin sound synthesis. The approach is based on a frame-weighted deconvolution of excitation and response signals. The excitation, consisting of bowed glissandi, is measured with piezoelectric transducers built into the bridge. Radiation responses are recorded in an anechoic chamber with multiple microphones placed at different angles around the violin. The proposed deconvolution algorithm computes impulse responses that, when convolved with any source signal (captured with the same transducer), produce a highly realistic violin sound very similar to that of a microphone recording. The use of motion sensors allows for tracking violin movements. Combining this information with the directional responses and using a dynamic convolution algorithm, helps to improve the listening experience by incorporating the violinist motion effect in stereo.


Random effects models in latent class analysis for evaluating accuracy of diagnostic tests.
When the results of a reference (or gold standard) test are missing or not error-free, the accuracy of diagnostic tests is often assessed through latent class models with two latent classes, representing diseased or nondiseased status. Such models, however, require that conditional on the true disease status, the tests are statistically independent, an assumption often violated in practice. Consequently, the model generally fits the data poorly. In this paper, we develop a general latent class model with random effects to model the conditional dependence among multiple diagnostic tests (or readers). We also develop a graphical method for checking whether or not the conditional dependence is of concern and for identifying the pattern of the correlation. Using the random-effects model and the graphical method, a simple adequate model that is easy to interpret can be obtained. The methods are illustrated with three examples from the biometric literature. The proposed methodology is also applicable when the true disease status is indeed known and conditional dependence could well be present.


Community Violence Exposure and Stress Reactivity in African American and Non-Latino White Adolescents With Overweight/Obesity.
Adolescents who experience community violence are exposed to toxic stressors at a critical period of growth and development. The purpose of this study was to examine the relationship between community violence exposure and stress reactivity in African American and non-Latino white adolescents with overweight/obesity. Fifty-one adolescents (47% female, 55% African American; aged 14-19) participated in this study. Community violence was assessed using the Survey of Children's Exposure to Community Violence. Stress reactivity was assessed via salivary cortisol and alpha-amylase area under the curve (AUC) during a Trier Social Stress Test (TSST). Race was a significant predictor of alpha-amylase reactivity (β = 10740±3665, p = 0.0006), with a higher alpha-amylase AUC observed in African American compared to non-Latino white adolescents. There was also a significant difference in the relationship between community violence exposure and alpha-amylase AUC by race (β = -3561±1226, p = 0.007). At similar increases in violence exposure, African Americans demonstrated a significant decline in alpha-amylase AUC while non-Latino whites demonstrated a significant increase in alpha-amylase AUC. Neither race nor violence exposure were significant predictors of cortisol AUC and there were no significant differences in the relationship between community violence exposure and cortisol AUC by race (all p's > .05). These preliminary findings suggest exposure to community violence may act to exacerbate autonomic dysregulation in African American adolescents with overweight/obesity. Longitudinal studies are needed to confirm the mechanisms by which community violence exposure differentially impacts stress responses by race.


Frontiers of model animals for neuroscience: two prosperous aging model animals for promoting neuroscience research.
A model animal showing spontaneous onset is a useful tool for investigating the mechanism of disease. Here, I would like to introduce two aging model animals expected to be useful for neuroscience research: the senescence-accelerated mouse (SAM) and the klotho mouse. The SAM was developed as a mouse showing a senescence-related phenotype such as a short lifespan or rapid advancement of senescence. In particular, SAMP8 and SAMP10 show age-related impairment of learning and memory. SAMP8 has spontaneous spongy degeneration in the brain stem and spinal cord with aging, and immunohistochemical studies reveal excess protein expression of amyloid precursor protein and amyloid β in the brain, indicating that SAMP8 is a model for Alzheimer's disease. SAMP10 also shows age-related impairment of learning and memory, but it does not seem to correspond to Alzheimer's disease because senile plaques primarily composed of amyloid β or neurofibrillary tangles primarily composed of phosphorylated tau were not observed. However, severe atrophy in the frontal cortex, entorhinal cortex, amygdala, and nucleus accumbens can be seen in this strain in an age-dependent manner, indicating that SAMP10 is a model for normal aging. The klotho mouse shows a phenotype, regulated by only one gene named α-klotho, similar to human progeria. The α-klotho gene is mainly expressed in the kidney and brain, and oxidative stress is involved in the deterioration of cognitive function of the klotho mouse. These animal models are potentially useful for neuroscience research now and in the near future.


Predictors of intensive care unit admission and related outcome for patients after pancreaticoduodenectomy.
High-volume centers have low morbidity and mortality after pancreaticoduodenectomy (PD). Less is known about treatment pathways and their influence on intensive care unit (ICU) utilization. Patients who underwent PD at a tertiary cancer center during the five-year period between January 1998 and December 2003 were identified from a prospective database. Preoperative and intraoperative factors relating to ICU admission and outcome were analyzed. Five hundred ninety-one pancreaticoduodenectomies were performed during the study period. Of these, 536 patients had complete records for analysis. Of the 536 patients, 51 (10%) were admitted to the ICU after surgery. Admission to the ICU was associated with decreased overall survival (P < .0001). Of the preoperative predictors of ICU admission, serum creatinine, albumin, and increased body mass index (BMI) were associated with ICU admission (P = .02, .05, and .002, respectively). Age, blood glucose, diagnosis of diabetes mellitus, and chronic obstructive pulmonary disease were not predictive of ICU admission on univariate analysis. Of the intraoperative factors, longer operative time and estimated blood loss (EBL) correlated with ICU admission (P = .003 and .0001, respectively). On multivariate analysis, only preoperative BMI and intraoperative EBL were independent predictors of ICU admission (P = .03 and .003, respectively). Patients with a preoperative BMI greater than 30 had a substantially higher risk of ICU admission (relative risk 2.4). The majority of patients who undergo PD do not require admission to the ICU. Factors most associated with ICU admission after PD are increased preoperative BMI and intraoperative blood loss.


Venular basement membranes ubiquitously express matrix protein low-expression regions: characterization in multiple tissues and remodeling during inflammation.
The venular basement membrane plays a critical role in maintaining the integrity of blood vessels and through its dense and highly organized network of matrix proteins also acts as a formidable barrier to macromolecules and emigrating leukocytes. Leukocytes can however penetrate the venular basement membrane at sites of inflammation, though the associated in vivo mechanisms are poorly understood. Using whole mount immunostained tissues and confocal microscopy, we demonstrate that the venular basement membrane of multiple organs expresses regions of low matrix protein (laminin-511 and type IV collagen) deposition that have been termed low-expression regions (LERs). In the multiple tissues analyzed (eg, cremaster muscle, skin, mesenteric tissue), LERs were directly aligned with gaps between adjacent pericytes and were more prevalent in small venules. As predicted by their permissive nature, LERs acted as "gates" for transmigrating neutrophils in all inflammatory reactions investigated (elicited by leukotriene B(4) [LTB(4)], CXCL1, tumor necrosis factor [TNF]alpha, endotoxin, and ischemia/reperfusion [I/R] injury), and this response was associated with an enhancement of the size of laminin-511 and type IV collagen LERs. Transmigrated neutrophils stained positively for laminins but not type IV collagen, suggesting that different mechanisms exist in remodeling of different basement membrane networks. Collectively the findings provide further insight into characteristics of specialized regions within venular basement membranes that are preferentially used and remodeled by transmigrating neutrophils.


Application of β-Glucosidase in a Biphasic System for the Efficient Conversion of Polydatin to Resveratrol.
Resveratrol, an ingredient of traditional Chinese medicine, has beneficial effects on human health and huge potential for application in modern medicine. Polydatin is extracted from plants and then deglycosylated into resveratrol; enzymatic methods are preferred for this reaction. In this study, a β-D-glucosidase from Sphingomonas showed high efficiency in transforming polydatin into resveratrol and was tolerant toward organic solvents. Applying this enzyme in a biphasic transformation system resulted in 95.3% conversion of 20% concentration crude polydatin to resveratrol in 4 h. We thus report a new method for high-efficiency, clean production of resveratrol.


Termination of obligate anoestrus and induction of fertile ovarian cycles in dogs by administration of purified pig LH.
The potential role of LH in the initiation of the follicular phase in dogs was investigated by treating anoestrous bitches with highly purified pig LH (n = 16) or saline (n = 8) three times a day for 7 days, beginning in either early anoestrus (days 94-116 of the cycle) or mid-anoestrus (days 124-145). Treatment with LH induced pro-oestrus within 7 days (n = 16), and oestrus (n = 12) and fertile ovulations (n = 7) at 16 + 3 days, while pro-oestrus in bitches treated with saline did not occur until 46-166 days after the start of treatment. Six of the seven ovulating bitches whelped normal litters. The bitches in which pro-oestrus but not oestrus occurred were all treated in early anoestrus. During treatment, plasma oestradiol in bitches treated with LH increased from 8 + 2 pg ml-1 to 20 + 5 pg ml-1 within 1 day, and reached higher peak values (45 + 7 pg ml-1) (P < 0.05) than those observed in saline-treated controls (9 + 3 ng ml-1). These results demonstrate that LH treatment alone can terminate anoestrus by inducing a normal follicular phase in dogs. The results also suggest that, in normal cyclic bitches, anoestrus is the result of insufficient LH secretion, and that spontaneous pro-oestrus could be the result of increased LH secretion in the presence of already adequate concentrations of FSH.


EM Golgi study on neurons of ectostriatum centrale in telencephalon of one-day-old chicken's brains.
In Golgi impregnated ectostriatum centrale of telencephalon of one-day-old chicken two types of neuron: projection neuron and interneuron with large axonal field and varicose axonal preterminals and terminals, were identified and examined in EM preparates. In the serial EM sections the morphological features of the two neurons types were observed. The projection neuron is characterized by the few axo-somatic synapses on the cell membrane, which are of symmetrical type. The INs, however, have numerous axo-somatic synapses on cell membrane both of symmetrical and asymmetrical types. Also the axonterminals were analysed.


Aggressive Care near the End of Life for Cancer Patients in Medicare Accountable Care Organizations.
To compare aggressiveness of end-of-life (EoL) care for older cancer patients attributed to Medicare Shared Savings Programs with that for similar fee for service (FFS) beneficiaries not in an accountable care organization (ACO) and examine whether observed differences in EoL care utilization vary across markets that differ in ACO penetration. Cross-sectional observational study comparing ACO-attributed beneficiaries with propensity score-matched beneficiaries not attributed to an ACO. A total of 21 hospital referral regions (HRRs) in the United States. Medicare FFS beneficiaries with a cancer diagnosis who were 66 years or older and died in 2013-2014. Outcome measures were claims-based quality measures of aggressive EoL care: (1) one or more intensive care unit (ICU) admissions in the last month of life, (2) two or more hospitalizations in the last month of life, (3) two or more emergency department visits in the last month of life, (4) chemotherapy 2 weeks or less before death, and (5) no hospice enrollment or hospice enrollment within 3 days of death. Analyses were adjusted for demographic and clinical characteristics of beneficiaries and practice characteristics. Compared with beneficiaries not in an ACO, ACO-attributed beneficiaries had a higher rate of ICU admission during the last month of life (37.7% vs 34.0%; adjusted difference = +2.8 percentage points; 95% confidence interval (CI) = 1.0-4.6) but fewer repeated hospitalizations (14.5% vs 15.2%; adjusted difference = -1.7 percentage points; CI = -3.1 to -.3). Other measures did not differ for the two groups. Although the ICU admission rates tended to decrease as ACO-penetration rates increased (P < .01), ACO patients had higher rates of ICU admission than non-ACO patients in both medium and high ACO-penetration HRRs. Cancer patients attributed to ACOs had fewer repeated hospitalizations but more ICU admissions in the last month of life than non-ACO patients; they had similar rates of other measures of aggressive care at the EoL. This suggests opportunities for ACOs to improve EoL care for cancer patients. J Am Geriatr Soc 67:961-968, 2019.


Activation of ribulose-1,5-bisphosphate carboxylase/oxygenase (rubisco) by rubisco activase : effects of some sugar phosphates.
The activation of purified ribulose-1,5-bisphosphate carboxylase/oxygenase (rubisco) has been studied in the presence of sugar phosphates, and the effect of rubisco activase on this process determined. During an 11-minute time course at pH 7.7 and 11 micromolar CO(2), the activation of rubisco was strongly inhibited by ribulose-1,5-bisphosphate (4 millimolar), fructose-1,6-bisphosphate (1 millimolar) and ribose 5-phosphate (5 millimolar), but this inhibition was overcome by the addition of rubisco activase and activation then proceeded to a greater extent than spontaneous activation of rubisco. Glycerate 3-phosphate (20 millomolar) slowed the initial rate but not the extent of activation and rubisco activase had no effect on this. The activation of rubisco was shown to be affected by phosphoenolpyruvate (3 millimolar) but not by creatine phosphate (3 millimolar) or ATP (3 millimolar), and the creatine-phosphate/creatine phosphokinase system was used to generate the high ATP/ADP quotients required for rubisco activase to function. ATP was shown to be required for the rubisco activase-dependent rubisco activation in the presence of fructose-1,6-bisphosphate (1 millimolar). It is concluded that rubisco activase has a mixed specificity for some sugar phosphate-bound forms of rubisco, but has low or no activity with others. Some possible bases for these differences among sugar phosphates are discussed but remain to be established.


Characterization of the purinergic receptor subtype on guinea-pig suburothelial myofibroblasts.
To identify particular purinoceptor subtypes by immunohistochemical labelling, as a layer of suburothelial myofibroblasts has been identified in the urinary bladder, and these cells respond to exogenous ATP by generating an intracellular Ca2+ transient, but the particular purinoceptor that responds to ATP is unclear. Tissue sections and isolated cells from the urothelial layer of the guinea-pig bladder were used. Preparations were labelled with primary antibodies to the intermediate-filament protein, vimentin, or the purinoceptors P2X3, P2Y1, P2Y2, P2Y4 and P2Y6. For single-labelling we used a secondary antibody tagged with the fluorescent marker Cy3, and for double-labelling also a secondary antibody tagged with fluorescein isothiocyanate or Cy2. Images were examined using a confocal microscope, with an argon (488 nm) or helium-neon (543 nm) laser. Vimentin-labelling was confined to the suburothelial layer and appeared as discrete signals. Isolated cells labelled with vimentin and strongly for the P2Y6 antibody. There was weaker staining for P2X3, P2Y2 and P2Y4, but none to P2Y1. With frozen sections there was P2Y6 labelling in the urothelial and suburothelial layer. The predominant purinoceptor in suburothelial myofibroblasts, from these labelling studies, is the P2Y6 subtype. However, there was weaker labelling to other subtypes, suggesting multiple receptor subtypes or heterogeneity of receptor subunits. The consequences of there being multiple purinoceptor subtypes in the suburothelial space with respect to sensory signalling are discussed.


Pericardial fat mimicking pericardial effusion on two-dimensional echocardiography.
A 78-year-old overweight woman with diabetes mellitus, bronchial asthma, and Sheehan's syndrome on chronic steroid therapy presented with mild short-lived hematemesis, significant hypotension disproportionate to the degree of bleeding and radiographic evidence of cardiomegaly. Endoscopy showed duodenal ulcer. During evaluation of the unexplained brief hypotension and cardiomegaly, 2D-echocardiogram demonstrated anterior and posterior echo-free spaces consistent with large pericardial effusion (PE). However, subsequent elective surgical pericardiotomy unexpectedly revealed large amounts of pericardial fat. Pericardial fat was also noted on magnetic resonance imaging of the chest. Our case illustrates a potential pitfall of 2D-echocardiography in the diagnosis of PE.


Results of external beam radiotherapy in patients with well differentiated thyroid carcinoma.
Surgical, thyroid hormone and radioactive 131I therapy are the standard curative treatments for well differentiated thyroid cancer. However, for residual, recurrent and nodal involvement of well differentiated thyroid cancer, external radiotherapy may be important in preventing distant metastases. The postoperative treatment of well differentiated human thyroid cancer with external radiotherapy is controversial. We retrospectively reviewed the records of 699 patients with papillary or follicular thyroid cancer, of whom 72 received external radiotherapy treatment after surgery. Thirty-two of these patients were at clinical stage 2 or 3 at the time of diagnosis while 172 patients at clinical stages 2 or 3 did not receive external radiotherapy after surgery. The patients who received external radiotherapy were older than those who did not (42.9 +/- 14.5 vs. 38.6 +/- 15.3), although this was not statistically significant. There were no significant differences in clinical parameters including surgical methods employed, histopathological types of cancer, follow-up stages, postoperative thyroglobulin levels, tumor size, accumulated 131I doses and survival rates between the two groups. To clarify the effect of external radiotherapy in patients with local invasion, we compared the survival rates of the patients with clinical stage 3 in the two groups and again no significant difference was found. During the follow-up period, 21 (28.4%) of the 72 patients who received external radiotherapy died of thyroid carcinoma. In our limited period of study, external radiotherapy did not improve the survival rate of patients with well differentiated thyroid cancer, though it appeared to cause temporary tumor regression.


Mechanical stability and clinical applicability assessment of novel orthodontic mini-implant design.
To compare the stability and clinical applicability of a novel orthodontic mini-implant design (N2) with the most widely used commercially available (CA) design. Two groups of mini-implants were tested: a CA design (1.5-mm diameter, 6-mm length) and N2 (3-mm diameter, 2-mm length, tapered shape). Implants were inserted in bone blocks of cortical bone simulation with varying densities (20 pounds per cubic foot [pcf], 30 pcf, and 40 pcf). A torque test was used to measure maximum insertion torque (MIT) and maximum removal torque (MRT). Compression and tension force vectors were applied at angles of 10°, 20°, 30°, and 40° using customized load pins to determine primary stability. Mean MIT and MRT were higher in the N2 than the CA design at all three cortical bone densities except MRT in 20 pcf bone (not statistically significant). The mean compression force required to displace the N2 at all distances and angulations was greater for the N2 than the CA design. At all displacement distances, the highest mean tension force required for N2 displacement was at 10° angulation, whereas at 30° and 40°, the mean tension force required to displace the CA design was greater. The primary stability of the N2 is superior to that of the CA design and is promising for both orthodontic and orthopedic clinical applicability, especially under compression force. The short length of the N2 reduces risk of damage to anatomic structures and root proximity during placement and orthodontic treatment. The stability of the N2 may be compromised in areas of high bone density and highly angulated tension force.


Influence of Football Match-Play on Isometric Knee Flexion Strength and Passive Hip Flexion Range of Motion in Football Referees and Assistant Referees.
The aim of this study was to examine the acute effect of officiating a football (soccer) match on isometric knee flexion strength and passive hip flexion range-of-motion (ROM) in referees and assistant football referees. Twelve referees (25.3 ± 3.3 years) and twenty-three assistant referees (25.1 ± 4.8 years) underwent measurements on isometric knee flexion strength and passive hip flexion ROM before and after officiating an official football match. Referees' and assistant referees' running patterns were monitored during the match using GPS technology. In comparison to pre-match values, referees reduced their isometric knee flexion strength (-12.36%, p = 0.046, Effect size [ES] = -0.36) in the non-dominant limb, while no significant differences were reported in the dominant limb (-0.75%, p = 0.833, ES = -0.02). No effect of the match was found in hip flexion ROM values in dominant (-4.78%, p = 0.102, ES = -0.15) and non-dominant limb (5.54%, p = 0.544, ES = 0.19). In assistant referees, the pre-to-post-match changes in isometric knee flexion strength (dominant limb -3.10%, p = 0.323, ES = -0.13; non-dominant limb -2.18%, p = 0.980, ES= 0.00) and hip flexion ROM (dominant limb 1.90% p = -0.816, ES = 0.13; non-dominant limb 3.22% p = 0.051, ES = 0.23) did not reach statistical significance. Officiating a match provoked a reduction in isometric knee flexion strength in the non-dominant limb of football referees, while no differences were reported in assistant referees.


One-year effects of vitamin D and calcium supplementation on chronic periodontitis.
A previous study reported by this group found that patients in periodontal maintenance programs taking vitamin D and calcium supplementation had a trend for better periodontal health compared to patients not taking supplementation. The objective of the present study is to determine, for the same cohort of subjects, whether such differences persist over a 1-year period. Fifty-one patients enrolled in maintenance programs from two dental clinics were recruited. Of these, 23 were taking vitamin D (≥400 IU/day) and calcium (≥1,000 mg/day) supplementation, and 28 were not. All subjects had at least two interproximal sites with ≥3 mm clinical attachment loss. For mandibular-posterior teeth, gingival index, plaque index, probing depth, attachment loss, bleeding on probing, calculus index, and furcation involvement were evaluated. Photostimulable-phosphor, posterior bitewing radiographs were taken to assess alveolar bone. Daily vitamin D and calcium intakes were estimated by nutritional analysis. Data were collected at baseline, 6 months, and 12 months. Total daily calcium and vitamin D intakes were 1,769 mg (95% confidence interval, 1,606 to 1,933) and 1,049 IU (781 to 1,317) in the taker group, and 642 mg (505 to 779) and 156 IU (117 to 195) in the non-taker group, respectively (P <0.001 for both). Clinical parameters of periodontal health improved with time in both groups (P <0.001). When clinical measures were considered collectively, the differences between supplement takers and non-takers had the following P values: baseline (P = 0.061); 6 months (P = 0.049); and 12 months (P = 0.114). After adjusting for covariates, the P values for the effect of supplementation were as follows: baseline (P = 0.028); 6 months (P = 0.034); and 12 months (P = 0.058). Calcium and vitamin D supplementation (≤1,000 IU/day) had a modest positive effect on periodontal health, and consistent dental care improved clinical parameters of periodontal disease regardless of such supplements. Our findings support the possibility that vitamin D may positively impact periodontal health and confirm the need for randomized clinical trials on the effects of vitamin D on periodontitis.


Cross-cultural boundary dilemmas: a graded-risk assessment approach.
Behavioral health professionals are constantly faced with the dilemma of how to define boundaries in their relationships with clients. When working with groups from diverse cultures, defining boundaries becomes even more complex. This article urges a flexible approach, using the graded-risk model (Martinez, 2000) and a list of cultural factors for clinicians to consider. Possible benefits of reaching out to clients in concrete ways, as well as risks, are emphasized. Clients' notions of appropriate boundaries must be considered in the decision-making process. Case examples from a refugee mental health clinic are used to elucidate a flexible approach to boundary decisions.


Stickiness to Glass: Circadian Changes in the Cell Surface of Chlamydomonas reinhardi.
Conditions were found in which Chlamydomonas reinhardi exhibits a circadian alteration of its cell surface, measured as ability to stick to glass. Under these same conditions the cells also show circadian rhythms of cell division and release of daughter cells. The three rhythmic phenomena were shown to have typical properties of rhythms controlled by the biological clock. The rhythm of stickiness was used to demonstrate that in a mixed culture containing two cell populations with natural periods differing by 2 to 3 hours, the cells did not mutally entrain each other and that this rhythm could be successfully applied in an enrichment procedure for mutants of the biological clock. Stickiness was shown to be independent of growth and motility of the cells and unaffected by red or far red illimination. Minimally sticking cells did not affect the sticking of maximally sticking cells in a mixed culture; nor was there a progressive increase in stickiness shown at the minimum from one cycle to the next in a pure culture. These results indicate that sticking probably is not mediated by long lived adhesive material or enzymes excreted into the medium. Several tests of the sensitivity of stickiness to replacement of the growth medium by distilled water or water containing various compounds suggest that ions might play an important role in the sticking reaction.


Survival of patients ≥70 years with advanced chronic kidney disease: Dialysis vs. conservative care.
The number of elderly patients with advanced chronic kidney disease (ACKD) has increased in recent years, and the best therapeutic approach has not been determined due to a lack of evidence. To observe the progression of elderly patients with ACKD (stages 4 and 5) and to compare the survival of stage 5 CKD patients with and without dialysis treatment. All patients ≥70 years who began ACKD follow-up from 01/01/2007 to 31/12/2008 were included, and their progression was observed until 31/12/2013. Demographic data, the Charlson comorbidity index, history of ischaemic heart disease (IHD) and diabetes mellitus (DM) were assessed. A total of 314 patients ≥70 years with stages 4 and 5 CKD were studied. Of these patients, 162 patients had stage 5 CKD at the beginning of follow-up or progressed to stage 5 during the study, and 69 of these patients were treated with dialysis. In the stage 5 group: median age was 77 years (74-81); 48% had IHD; 50% had DM, Charlson 7 (6-9). Kaplan-Meier survival analysis: ≥70 years (93 vs. 69 patients with dialysis, log rank: 15 P<.001); patients ≥75 years (74 vs. 46 patients with dialysis, log rank: 8.9 P=.003); patients ≥80 (40 vs. 15 patients with dialysis) and p=0,2. Patients receiving dialysis were younger, with a lower Charlson comorbidity index and shorter follow-up time. Our study shows that dialysis treatment improves survival, although this benefit is lost in patients ≥80 years.


Inter- and intramolecular-bridge-mediated electron transfer in aliphatic halides.
The anionic surfaces of the 1-chloro- and 4-chlorobicyclo[2.2.1]heptan-2-one, 1-chloro- and 4-chlorobicyclo[2.2.2]octan-2-one, 1-chloro- and 5-chloroadamantan-2-one, and 2-chlorotricyclo[126.96.36.199(2,7)]tridecan-13-one were explored using DFT functionals with full geometry optimization in solution. The reductive cleavage of these compounds is controlled by the rigidity of the polycycle, its capability to form an unstrained radical, and by the relative carbonyl/C-Cl disposition on the bridge. Such control can be exerted by either a concerted-dissociative or a stepwise mechanism with radical anions as intermediates. 5-Chloroadamantan-2-one is the most suitable compound to follow the latter pathway.


Use of Polymeric Nanoparticle Platform Targeting the Liver To Induce Treg-Mediated Antigen-Specific Immune Tolerance in a Pulmonary Allergen Sensitization Model.
Nanoparticles (NPs) can be used to accomplish antigen-specific immune tolerance in allergic and autoimmune disease. The available options for custom-designing tolerogenic NPs include the use of nanocarriers that introduce antigens into natural tolerogenic environments, such as the liver, where antigen presentation promotes tolerance to self- or foreign antigens. Here, we demonstrate the engineering of a biodegradable polymeric poly(lactic- co-glycolic acid) (PLGA) nanocarrier for the selective delivery of the murine allergen, ovalbumin (OVA), to the liver. This was accomplished by developing a series of NPs in the 200-300 nm size range as well as decorating particle surfaces with ligands that target scavenger and mannose receptors on liver sinusoidal endothelial cells (LSECs). LSECs represent a major antigen-presenting cell type in the liver capable of generating regulatory T-cells (Tregs). In vitro exposure of LSECs to NPOVA induced abundant TGF-β, IL-4, and IL-10 production, which was further increased by surface ligands. Animal experiments showed that, in the chosen size range, NPOVA was almost exclusively delivered to the liver, where the colocalization of fluorescent-labeled particles with LSECs could be seen to increase by surface ligand decoration. Moreover, prophylactic treatment with NPOVA in OVA-sensitized and challenged animals (aerosolized inhalation) could be seen to significantly suppress anti-OVA IgE responses, airway eosinophilia, and TH2 cytokine production in the bronchoalveolar lavage fluid. The suppression of allergic airway inflammation was further enhanced by attachment of surface ligands, particularly for particles decorated with the ApoB peptide, which induced high levels of TGF-β production in the lung along with the appearance of Foxp3+ Tregs. The ApoB-peptide-coated NPs could also interfere in allergic airway inflammation when delivered postsensitization. The significance of these findings is that liver and LSEC targeting PLGA NPs could be used for therapy of allergic airway disease, in addition to the potential of using their tolerogenic effects for other disease applications.


Responder cells in the human autologous mixed lymphocyte reaction.
Isolated human T4+ cells proliferate in the autologous mixed lymphocyte reaction (AMLR), whereas isolated T8+ cells do not. However, in the presence of Interleukin 2 or T4+ cells, the T8+ cells demonstrated substantial proliferation. These studies suggest that T8+ cells recognize signals from autologous non-T cells, but require an additional factor for the subsequent proliferative response. Since this stimulus can be provided by T4+ cells, the AMLR appears to constitute an inducer circuit. Different defects in this circuit may be responsible for the common abnormality of the AMLR in different diseases.


Morphological study of accessory gland of Bothrops jararaca and its secretory cycle.
The venom gland apparatus of Bothrops jararaca is composed of four distinct parts: main venom gland, primary duct, accessory gland and secondary duct. Despite the numerous studies concerning morphology and venom production and secretion in the main venom gland, there are few studies about the accessory gland and its secretion. We characterized the accessory gland of B. jararaca snake and determined the secretion cycle by morphological analysis using light and transmission electron microscopy. Our data showed that the accessory gland of B. jararaca has a simple secretory epithelium with at least six types of cells in the anterior region: two types of secretory cells, mitochondria-rich cells without secretory vesicles, horizontal cells, dark cells and basal cells, and in the posterior region a simple epithelium with two types of cells: seromucous cells and horizontal cells. Furthermore, the mucous secretory cells of the accessory gland show a delayed and massive exocytosis that occurs four days after the extraction of venom. Morphological analysis at different steps after venom extraction showed that the accessory gland has a long cycle of production and secretion, which is not synchronous with the main venom gland secretory cycle.


The metal homeostasis protein, Lsp, of Streptococcus pyogenes is necessary for acquisition of zinc and virulence.
"Cluster 9" family lipoproteins function as ligand-binding subunits of ABC-type transporters in maintaining transition metal homeostasis and have been implicated in the virulence of several bacteria. While these proteins share high similarity, the specific metal that they recognize and whether their role in virulence directly involves metal homeostasis cannot be reliably predicted. We examined the cluster 9 protein Lsp of Streptococcus pyogenes and found that specific deletion of lsp produced mutants highly attenuated in a murine model of soft tissue infection. Under standard in vitro conditions, growth of the Lsp(-) mutant was indistinguishable from that of the wild type, but growth was defective under zinc-limited conditions. The growth defect could be complemented by plasmids expressing wild-type Lsp but not Lsp engineered to lack its putative lipidation residue. Furthermore, Zn(2+) but not Mn(2+) rescued Lsp(-) growth, implicating Zn(2+) as the physiological ligand for Lsp. Mutation of residues in the putative Zn(2+)-binding pocket generated variants both hypo- and hyper-resistant to zinc starvation, and both mutant classes displayed attenuated virulence. Together, these data suggest that Lsp is a ligand-binding component of an ABC-type zinc permease and that perturbation of zinc homeostasis inhibits the ability of S. pyogenes to cause disease in a zinc-limited host milieu.


Electrodecoration and Characterization of Superparamagnetic Iron Oxide Nanoparticles with Bioactive Synergistic Nanocopper: Magnetic Hyperthermia-Induced Ionic Release for Anti-Biofilm Action.
The urgency for the availability of new antibacterial/disinfectant agents has become a worldwide priority. At the same time, along with the extensive use of other metal nanoparticles (NPs), the investigation of magnetic NPs (MNPs) in antibacterial studies has turned out to be an increasingly attractive research field. In this context, we present the preparation and characterization of superparamagnetic iron oxide NPs, electrodecorated with antimicrobial copper NPs, able to modulate the release of bioactive species not only by the NP's stabilizer, but also through the application of a suitable magnetic field. Antimicrobial synergistic CuNPs stabilized by benzalkonium chloride have been used in the current study. We demonstrate the successful preparation of Cu@Fe3O4 MNPs composites through morphological and spectroscopic results. Additionally, an extensive magnetic characterization is reported, along with hyperthermia-induced copper ionic release. On the basis of our results, we propose a new generation of antimicrobial magnetic nanomaterials, whose bioactivity can be also tuned by the application of a magnetic field.


Nucleus accumbens responses differentiate execution and restraint in reward-directed behavior.
Our behavior is powerfully driven by environmental cues that signal the availability of rewarding stimuli. We frequently encounter stimuli-a bowl of candy or an alert from our smartphone-that trigger actions to obtain those rewards, even though there may be positive outcomes associated with not acting. The inability to restrain one's action in the presence of reward-associated cues is one type of impulsive behavior and a component of such maladaptive behaviors as overeating, gambling, and substance abuse. The nucleus accumbens (NAc) is ideally situated to integrate multiple cognitive and affective inputs to bias action via outputs through the basal ganglia. NAc neurons have been shown to respond to cues that predict reward availability, goal-directed behaviors aimed at obtaining them, and delivery of the reward itself. As these processes are typically associated, it is difficult to discern whether signals in the NAc are more closely related to processing reward-predictive aspects of goal-directed behavior or selection of behavioral response. To dissociate these possibilities, we recorded the activity of NAc neurons while rats performed a task in which two different cues both informed rats of reward availability but required them to either press a lever (Go) or withhold pressing (NoGo) to obtain the reward. Individual cue-responsive neurons showed either increases or decreases in activity at cue onset. Increases in activity were larger, and decreases smaller, when rats withheld lever pressing, whether correctly for NoGo trials or in error on Go trials. Thus NAc cue responses correlated with action, regardless of cue type or accuracy.


VHL and FHIT locus loss of heterozygosity is common in all renal cancer morphotypes but differs in pattern and prognostic significance.
Deletions involving 3p are believed to be typical for conventional (clear cell) renal cell carcinoma (cRCC), with confirmed and suspected targets being the VHL and FHIT tumor suppressor genes, respectively. By contrast, 3p deletions are felt to be rare in papillary RCC (pRCC) and chromophobe RCC (chRCC); however, this belief is based on relatively scant data. In particular, 3p14.2 deletions, possibly resulting in FHIT inactivation, have been rarely studied in pRCC or chRCC even though they may be relevant in early renal tumorigenesis. We therefore examined 3p deletion rates and patterns in pRCC and chRCC with particular attention to 3p14.2. We examined 16 chRCCs and 27 pRCCs for loss of heterozygosity (LOH) at 3p25-26 and 3p14.2 using 13 well-mapped microsatellite markers. Those pRCC with LOH at 3p25-26 were also screened for VHL gene mutations. The results were correlated with tumor histology and patient outcome and compared with data we had obtained previously on cRCC. We found similar overall 3p LOH rates in pRCC (59%), chRCC (86.6%), and cRCC (75.8%). In pRCC and chRCC, LOH at 3p25-26 was more common than at 3p14.2, whereas the converse was true for cRCC. In the pRCC with 3p25-26 LOH, we confirmed that this was not associated with mutations of the VHL gene. At 3p14.2, LOH rates of pRCC were lower than those of cRCC and chRCC (p<0.02). All morphotypes showed a predominately interstitial LOH pattern, which was most pronounced in the 3p14.2 region in cRCC. 3p LOH in chRCC was associated with improved patient outcome, mirroring our previous cRCC data. We conclude that 3p LOH is a universal phenomenon in RCC, but has different underlying mechanisms, molecular targets, and implications in the different morphotypes, although FHIT inactivation may play a role in both cRCC and chRCC tumorigenesis.


Adenosinergic Signaling as a Key Modulator of the Glioma Microenvironment and Reactive Astrocytes.
Astrocytes are numerous glial cells of the central nervous system (CNS) and play important roles in brain homeostasis. These cells can directly communicate with neurons by releasing gliotransmitters, such as adenosine triphosphate (ATP) and glutamate, into the multipartite synapse. Moreover, astrocytes respond to tissue injury in the CNS environment. Recently, astrocytic heterogeneity and plasticity have been discussed by several authors, with studies proposing a spectrum of astrocytic activation characterized by A1/neurotoxic and A2/neuroprotective polarization extremes. The fundamental roles of astrocytes in communicating with other cells and sustaining homeostasis are regulated by purinergic signaling. In the CNS environment, the gliotransmitter ATP acts cooperatively with other glial signaling molecules, such as cytokines, which may impact CNS functions by facilitating/inhibiting neurotransmitter release. Adenosine (ADO), the main product of extracellular ATP metabolism, is an important homeostatic modulator and acts as a neuromodulator in synaptic transmission via P1 receptor sensitization. Furthermore, purinergic signaling is a key factor in the tumor microenvironment (TME), as damaged cells release ATP, leading to ADO accumulation in the TME through the ectonucleotidase cascade. Indeed, the enzyme CD73, which converts AMP to ADO, is overexpressed in glioblastoma cells; this upregulation is associated with tumor aggressiveness. Because of the crucial activity of CD73 in these cells, extracellular ADO accumulation in the TME contributes to sustaining glioblastoma immune escape while promoting A2-like activation. The present review describes the importance of ADO in modulating astrocyte polarization and simultaneously promoting tumor growth. We also discuss whether targeting of CD73 to block ADO production can be used as an alternative cancer therapy.


[Cardiovascular responses to resistance exercise are affected by workload and intervals between sets.]
BACKGROUND: The control of cardiovascular responses during resistance exercise (RE) is important for patient safety. OBJECTIVE: To investigate the influence of repetition maximum (RM) and rest interval between sets (RI) on heart rate (HR), systolic blood pressure (SBP) and rate-pressure product (RPP) during RE. METHODS: Twenty healthy subjects (26 +/- 5 years of age) underwent RE protocols involving three sets of leg press (6 and 12 RM) and RI proportional to the contraction time (1:3 and 1:5). The HR was checked on a continuous basis by using a cardiotachometer and the SBP was checked at the end of the sets, via a protocol validated by the auscultatory method. RESULTS: The HR was influenced by the workload (p = 0.008) and sets (p < 0.001), but not by the RI (p = 0.087). The SBP suffered from the isolated effect of the number of sets (p < 0.001) and RI (p = 0.017), but not from the workload (p = 0.95). The RPP rose in direct proportion to the workload (p = 0.036) and sets (p < 0.001), but in inverse proportion to the RI (p = 0.006). In 6 RM protocols, the variation in the HR was higher for RI = 1:3 (Delta = 11.2 +/- 1.1 bpm) than for RI = 1:5 (Delta = 4.5 +/- 0.2 bpm; p = 0.002), but there was no difference for 12 RM (Delta 1:3 = 21.1 +/- 2.2 bpm; Delta 1:5 = 18.9 +/- 2.0 bpm, p = 0.83). The RI influenced the variation in SBP in all loads (6 RM - Delta 1:3 = 10.6 +/- 0.9 mmHg, Delta 1:5 = 6.6 +/- 0.7 mmHg; p = 0.02 and 12 RM - Delta 1:3 = 15.2 +/- 1.1 mmHg, Delta 1:5 = 8.4 +/- 0.7 mmHg; p = 0.04). The RPP rose in proportion to the workload (p = 0.036) and to the sets (p < 0.001), but in inverse proportion to the RI (p = 0.006). With RI = 1:3, there was difference in RPP for 6 RM (Delta = 2,892 +/- 189 mmHg.bpm) and 12 RM (Delta = 4,587 +/- 300 mmHg.bpm; p = 0.018), but not with RI = 1:5 (6 RM: Delta = 1,224 +/- 141 mmHg.bpm, 12 RM: Delta = 2,332 +/- 194 mmHg.bpm; p = 0.58). CONCLUSION: Regardless of the workload, an increased RI was associated with lower cardiovascular responses during RE, especially of SBP.


A retrospective comparative study of postoperative sagittal balance in isthmic L5-S1 spondylolisthesis using single segment or two-segment pedicle screw fixation.
To compare the radiographic parameters and clinical outcomes of isthmic L5-S1 spondylolisthesis with single segment or two-segment pedicle screw fixation. Between January 2018 and January 2019, a total of 76 patients with isthmic L5-S1 spondylolisthesis were included in this study. All patients were treated with varying numbers of pedicle screw fixation with single-segment fusion during posterior lumbar interbody fusion (PLIF). Patients were divided into two groups, based on the number of pedicle screws placed during fixation, namely, 4 screws (4S) group and 6 screws (6S) group. Subsequently, the sagittal balance parameters were measured, which included slippage degree (SD), lumbar lordosis (LL), segmental lordosis (SL), pelvic incidence (PI), pelvic tilt (PT), sacral slope (SS), and sagittal vertical axis (SVA). Clinical functional outcomes were assessed using the visual analog scale (VAS) for back pain and the oswestry disability index (ODI) scores. The 4S group comprised of 10 males and 27 females, with a median age of 55.2 ± 10.8 years old and a mean follow-up of 16.95 ± 4.16 months. The 6S group comprised of 14 males and 25 females, with a median age of 58.1 ± 7.5 years old and a median follow-up of 17.33 ± 3.81 months. No significant differences were evident in all preoperative parameters between both groups. In contrast, the postoperative LL, SL, PT, SS, and SD values increased significantly, compared to the preoperative values in both groups (all P < 0.05). At the last follow-up, the 6S group exhibited better correction in LL, SL, and PT, relative to the 4S group (all P < 0.05). A significant SD difference was observed between both groups at all points post surgery (P < 0.05). The postoperative slip correction rate was significantly larger in the 6S group, compared to the 4S group (P < 0.05). The postoperative VAS and ODI scores of both groups improved significantly, when compared to the preoperative scores (both P < 0.05). However, there were no significant differences in the ODI and VAS scores between the two groups at all time points. The clinical outcomes of both approaches appeared to be satisfactory. In terms of short-term outcomes, the 6S group exhibited better spinal sagittal restoration and stability than the 4S group.


Hierarchically Structured Surfaces Prepared by Phase Separation: Tissue Mimicking Culture Substrate.
The pseudo 3D hierarchical structure mimicking in vivo microenvironment was prepared by phase separation on tissue culture plastic. For surface treatment, time-sequenced dosing of the solvent mixture with various concentrations of polymer component was used. The experiments showed that hierarchically structured surfaces with macro, meso and micro pores can be prepared with multi-step phase separation processes. Changes in polystyrene surface topography were characterized by atomic force microscopy, scanning electron microscopy and contact profilometry. The cell proliferation and changes in cell morphology were tested on the prepared structured surfaces. Four types of cell lines were used for the determination of impact of the 3D architecture on the cell behavior, namely the mouse embryonic fibroblast, human lung carcinoma, primary human keratinocyte and mouse embryonic stem cells. The increase of proliferation of embryonic stem cells and mouse fibroblasts was the most remarkable. Moreover, the embryonic stem cells express different morphology when cultured on the structured surface. The acquired findings expand the current state of knowledge in the field of cell behavior on structured surfaces and bring new technological procedures leading to their preparation without the use of problematic temporary templates or additives.