Do extra-group fertilizations increase the potential for sexual selection in male mammals?
Fertilizations by males outside the social breeding group (extra-group paternity, EGP) are widespread in birds and mammals. EGP is generally proposed to increase male reproductive skew and thereby increase the potential for sexual selection, but the generality of this relationship is unclear. We extracted data from 27 mammals in seven orders and used phylogenetic comparative methods to investigate the influence of EGP and social mating system on measures of inequality in male fertilization success, which are indices of the potential for sexual selection. We find that EGP and social mating system can predict the potential for sexual selection in mammalian populations, but only when considered jointly and not individually. EGP appears to increase the potential for sexual selection but only when the degree of social polygyny is relatively low. When social polygyny is high, EGP appears to result in a more uniform distribution of reproduction and a decrease in the potential for sexual selection. A possible explanation to be investigated is that the phenotype of extra-group fathers differs systematically across social mating systems. Our findings have implications for the use of EGP and social mating system as indices of sexual selection in comparative analyses of trait evolution under sexual selection.


[Application of iPDMS protein microarray in screening of tumor-associated antigen autoantibodies].
The rapid screening of tumor markers is a challenging task for early diagnosis of cancer. This study aims to use highly sensitive chemiluminescent protein microarray technology to efficiently screen a variety of low abundance tumor related markers. A new material, termed integrated polydimethylsiloxane modified silica gel (iPDMS), was obtained by adding a surface polymerization initiator with olefin end to the conventional polydimethylsiloxane, and fixing into the three-dimensional structure of polydimethylsiloxane by thermal crosslinking through silicon hydrogen bonding. In order to make the iPDMS material resistant to non-specific protein adsorption, a poly(OEGMA) polymer brush was synthesized by surface-initiated atom transfer radical polymerization at the active initiation site. Finally, 20 tumor-related antigens were printed into the specific areas of the microarray by high-throughput spray printing technology, and assembled into 48-well detection microtiterplates of the iPDMS microarray. It was found the VEGFR and VEGF121 autoantibodies that obtained from 8 common tumors (breast cancer, lung cancer, colon cancer, gastric cancer, liver cancer, leukemia, lymphoma and ovarian cancer) can be used as potential tumor markers. The chemiluminescence labeled iPDMS protein microarray can be used for the screening of tumor autoantibodies at early stage.


[Levels of histone H3 acetylation in peripheral blood mononuclear cells of acute cerebral infarction patients].
To observe the co-variation of acetylated histone H3 levels of peripheral blood mononuclear cells (PBMCs) and onset time of acute ischemic stroke and examine the histone H3 acetylation levels in PBMCs of acute cerebral infarction patients with different stroke subtypes and injury degrees. The peripheral blood samples 2 ml from patients at different timepoints (1, 3, 5, 7, 14 d) from April 2013 to July 2013 and normal controls were collected to observe the dynamic change of Ac-H3 levels of PBMCs in cerebral infarction patients. Also between April 2013 and October 2013, blood samples from 103 patients within 7 d after acute ischemic stroke were collected. Global histone was extracted by assay kit and differential histone H3 acetylation levels were determined by Western blot. All patients were measured by the Oxfordshire Community Stroke Project (OCSP) classification and National Institutes of Health Stroke Scale (NIHSS) score. The levels of acetylated histone H3 in PBMCs of acute cerebral infarction patients started to decrease as early as 1 d and remained below those normal controls for at least 7 d after stroke. It fulfilled the minimum at 3 d after infarction (P < 0.001). Acetylated histone H3 levels of PBMCs differed in OCSP classification (P < 0.05) and reached a nadir in TACI group. Histone H3 acetylation levels of PBMCs were major affecting factors of neurological injury severity and negatively correlated with it through multiple regressive analysis (β = -0.297, P = 0.001). Histone H3 acetylation level in PBMCs of acute cerebral infarction patients is lower than healthy persons. And it decreases markedly in TACI group and patients with severe neurological dysfunction.


Magnetic resonance angiography with midsagittal saturation for the assessment of blood flow from superficial temporal artery-to-middle cerebral artery bypass.
The purpose of this study was to evaluate the feasibility of magnetic resonance angiography (MRA) with midsagittal saturation for depiction of superficial temporal artery-to-middle cerebral artery bypass flow. Eleven patients undergoing bypass surgery in 13 regions were examined by external carotid artery angiography (ECAG) and 3-dimensional time-of-flight MRA with saturation pulse applied to the midsagittal plane covering the internal carotid arteries. We classified the extent of visualization of bypass flow into 4 types and examined the agreement of findings between them. The MRA revealed types of bypass flow in agreement with those observed on ECAG in 10 of the 13 regions. The MRA underestimated bypass flow in 2 regions and overestimated it in 1 region. The MRA with midsagittal saturation demonstrated bypass flow in agreement with ECAG in most cases. Application of MRA with midsagittal saturation permits noninvasive assessment of physiological flow from superficial temporal artery-to-middle cerebral artery bypass for a postoperative follow-up.


In vitro ocular irritation toxicity study of some pesticides.
The use of animals in toxicological screening is a controversial issue. The Draize eye irritation test receives particular criticism because of the injuries inflicted on the test animals. In recent years various in vitro methods have been developed to replace the heavily criticised Draize rabbit eye test for irritation testing. One of the best-studied alternative methods is the Hen's Egg Test-Chorioallantoic Membrane (HET-CAM). In the present studies comparative screening was performed with a set of pesticides to establish parallel data on in vitro (HET-CAM) and in vivo (Draize) results. The tested pesticides included Arelon 500 FW (isoproturon), Banvel 480 (dicamba), Dikamin D (2.4 D), Karathane LC (dinocap), Ronstar (oxadiazon) and Modown 4 F (bifenox). In most cases a good correlation was found between the HET-CAM assessment and results of the Draize rabbit eye test. Although the current form of the HET-CAM test is a valuable prescreen method for predicting the ocular irritation potential of chemicals, and can be used for reducing the number of experimental animals, a number of technical problems must still be addressed before these systems can replace whole animal tests. The HET-CAM test can be a useful component of a battery of tests needed for replacing the Draize rabbit eye test.


Optical properties of ice and snow.
The interactions of electromagnetic radiation with ice, and with ice-containing media such as snow and clouds, are determined by the refractive index and absorption coefficient (the 'optical constants') of pure ice as functions of wavelength. Bulk reflectance, absorptance and transmittance are further influenced by grain size (for snow), bubbles (for glacier ice and lake ice) and brine inclusions (for sea ice). Radiative transfer models for clouds can also be applied to snow; the important differences in their radiative properties are that clouds are optically thinner and contain smaller ice crystals than snow. Absorption of visible and near-ultraviolet radiation by ice is so weak that absorption of sunlight at these wavelengths in natural snow is dominated by trace amounts of light-absorbing impurities such as dust and soot. In the thermal infrared, ice is moderately absorptive, so snow is nearly a blackbody, with emissivity 98-99%. The absorption spectrum of liquid water resembles that of ice from the ultraviolet to the mid-infrared. At longer wavelengths they diverge, so microwave emission can be used to detect snowmelt on ice sheets, and to discriminate between sea ice and open water, by remote sensing. Snow and ice are transparent to radio waves, so radar can be used to infer ice-sheet thickness. This article is part of the theme issue 'The physics and chemistry of ice: scaffolding across scales, from the viability of life to the formation of planets'.


Dosing profile profoundly influences nicotinic acid's ability to improve metabolic control in rats.
Acute nicotinic acid (NiAc) administration results in rapid reduction of plasma FFA concentrations. However, sustained NiAc exposure is associated with tolerance development resulting in return of FFA to pretreatment levels. The aim of this study was to determine whether a 12 h rectangular exposure profile (intermittent dose group) could avoid tolerance development and thereby reverse insulin resistance induced by lipid overload. FFA lowering was assessed in male Sprague Dawley (lean) and obese Zucker rats (obese) in response to a 5 h NiAc infusion, in either NiAc-naïve animals or after 5 days of continuous (24 h/day) or intermittent (12 h/day) NiAc dosing (via implantable, programmable minipump). We found that intermittent dosing over 5 days preserved NiAc-induced FFA lowering, comparable to dosing in NiAc-naïve animals. By contrast, following 5 days continuous administration, NiAc-induced FFA lowering was lost. The effect of intermittent NiAc infusion on insulin sensitivity was assessed in obese Zucker rats using hyperinsulinemic-isoglycemic clamps. The acute effect of NiAc to elevate glucose infusion rate (vs. saline control) was indeed preserved with intermittent dosing, while being lost upon continuous infusion. In conclusion, an intermittent but not continuous NiAc dosing strategy succeeded in retaining NiAc's ability to lower FFA and improve insulin sensitivity in obese Zucker rats.-Kroon, T., A. Kjellstedt, P. Thalén, J. Gabrielsson, and N. D. Oakes.


Analysis of spontaneous inquiries about suspected adverse drug reactions posted by the general public on the electronic Japanese bulletin board "Yahoo! Japan Chiebukuro".
Spontaneous inquiries about the development of adverse drug reactions (ADRs) to medicines can be extracted based on the questions posted by the general public on the electronic Japanese bulletin board "Yahoo! Japan Chiebukuro". Our aim was to clarify the characteristics related to people's descriptions of suspected ADRs and determine the reasons for submitting a spontaneous inquiry. Fifty brand names of medicines used for inquiry extraction were chosen by selecting 35 pharmaceutical products, based on the generic names that had the highest sales in Japan. Questions containing both the brand name of one of these medicines and the term "Fukusayō" (ADR in Japanese) that were posted from July 2004 to June 2009 were extracted from the site. Among 1,419 questions extracted, 614 questions had at least one identifiable brand name of a suspected medicine, an ADR description, and the extent to which the ADR appeared to be caused by the suspected medicine(s). Among these 614 questions, 589 described in detail the symptoms/signs that the inquirers themselves or their families had experienced as ADRs. The highest number of questions was found for Paxil (525). Posts asking whether the symptoms being experienced were due to an ADR accounted for the highest number of questions. In most cases, the inquirer suspected that a single medicine led to an ADR and was seeking advice from others taking the same medicine. Our examination of spontaneous inquiries showed that people have sufficient knowledge to adequately report potential ADRs in terms of their symptoms, suspected medicines, and the disease for which the medicine was used. However, they often did not describe the start time when the ADR appeared or when the suspected medicine was started.


Elucidating the Limiting Steps in Sulfuric Acid-Base New Particle Formation.
The molecular interactions between sulfuric acid (sa) and methylamine (ma) are investigated using computational methods. The molecular structures and vibrational frequencies of (sa)a(ma)b clusters, with a, b ≤ 4, were obtained with the ωB97X-D functional using a 6-31++G(d,p) basis set. The single-point energies were corrected using the domain-based local pair natural orbital coupled cluster method-DLPNO-CCSD(T)-with an aug-cc-pVTZ basis set. The calculated Gibbs free energies (ΔG) of the clusters are used to calculate the evaporation rates of the (sa)a(ma)b cluster system and compare them to the corresponding ammonia clusters. With the atmospheric cluster dynamics code (ACDC), the new particle formation rates of the (sa)a(ma)b clusters were simulated and compared to the (sa)a(dma)b cluster system. It is found that methylamine is not capable of explaining observed new particle formation event in the ambient atmosphere. Looking into the calculated Gibbs free energy profiles it is found that the limiting steps in forming stable (sa)3-4(base)3-4 clusters depend strongly on the formation of the (sa)1(base)1 and (sa)2(base)2 clusters. These findings further support that compounds with high basicity are required to form the very initial cluster nucleus, which serves as the basis for forming new particles in the atmosphere.


Disentangling bias between Gq, GRK2, and arrestin3 recruitment to the M3 muscarinic acetylcholine receptor.
G protein-coupled receptors (GPCRs) transmit extracellular signals to the inside by activation of intracellular effector proteins. Different agonists can promote differential receptor-induced signaling responses - termed bias - potentially by eliciting different levels of recruitment of effector proteins. As activation and recruitment of effector proteins might influence each other, thorough analysis of bias is difficult. Here, we compared the efficacy of seven agonists to induce G protein, G protein-coupled receptor kinase 2 (GRK2), as well as arrestin3 binding to the muscarinic acetylcholine receptor M3 by utilizing FRET-based assays. In order to avoid interference between these interactions, we studied GRK2 binding in the presence of inhibitors of Gi and Gq proteins and analyzed arrestin3 binding to prestimulated M3 receptors to avoid differences in receptor phosphorylation influencing arrestin recruitment. We measured substantial differences in the agonist efficacies to induce M3R-arrestin3 versus M3R-GRK2 interaction. However, the rank order of the agonists for G protein- and GRK2-M3R interaction was the same, suggesting that G protein and GRK2 binding to M3R requires similar receptor conformations, whereas requirements for arrestin3 binding to M3R are distinct.


Angiotensin II type 1 (AT1) receptor-mediated accumulation of angiotensin II in tissues and its intracellular half-life in vivo.
Angiotensin II (Ang II) is internalized by various cell types via receptor-mediated endocytosis. Little is known about the kinetics of this process in the whole animal and about the half-life of intact Ang II after its internalization. We measured the levels of 125I-Ang II and 125I-Ang I that were reached in various tissues and blood plasma during infusions of these peptides into the left cardiac ventricle of pigs. Steady-state concentrations of 125I-Ang II in skeletal muscle, heart, kidney, and adrenal were 8% to 41%, 64% to 150%, 340% to 550%, and 680% to 2100%, respectively, of the 125I-Ang II concentration in arterial blood plasma (ranges of six experiments). The tissue concentrations of 125I-Ang I were less than 5% of the arterial plasma concentrations. 125I-Ang II accumulation seen in heart, kidney, and adrenal was almost completely blocked by a specific Ang II type 1 (AT1) receptor antagonist. Steady-state concentrations of 125I-Ang II were reached within 30 to 60 minutes in the tissues and within 5 minutes in blood plasma. The in vivo half-life of intact 125I-Ang II in heart, kidney, and adrenal was approximately 15 minutes, compared with 0.5 minute in the circulation. Thus, Ang II, but not Ang I, from the circulation is accumulated by some tissues, and this is mediated by AT1 receptors. The time course of this process and the long half-life of the accumulated Ang II support the contention that this Ang II has been internalized after its binding to the AT1 receptor, so that it is protected from rapid degradation by endothelial peptidases. The results of this study are in agreement with growing evidence of an important physiological role for internalized Ang II.


Blood components in neonatal medicine.
During a six-month period, 552 infants were admitted to a level III Neonatal Intensive Care Unit (NICU) and four level II units. Of the 953 cross matches of blood components requested from the blood bank, 83% were administered. Forty-four percent of the infants received multiple blood transfusions from multiple blood donors (mean 3.9 donors, range two to 11). Thirty-one percent received multiple transfusions from only one donor. The mean total volume of blood given was 22.5 ml (range 3 to 120 ml), exclusive of blood used for exchange transfusions. Seventy percent of the blood components were given to infants weighing less than 2,500 gm, and 44% were given to infants weighing less than 1,500 gm. Hospitals having only level II units must have the same blood banking facilities as hospitals with level III units, since 21% of the infants given transfusion received the blood component while receiving level II care.


Nephron sparing surgery is a feasible and efficient treatment of T1a renal cell carcinoma in kidney transplant: a prospective series from a single center.
Renal cell carcinoma in a renal graft is a rare condition whose incidence will increase in the future. To our knowledge no standardized treatment has been established for this disease. We performed a prospective study of nephron sparing surgery for small renal cell carcinoma in renal grafts. From January 2002 to December 2006, 2,050 renal graft recipients were followed at our transplantation center. Of these patients 7 were diagnosed with histologically confirmed renal cell carcinoma in the renal graft, 5 of whom presented with T1a renal cell carcinoma and prospectively underwent nephron sparing surgery. Five patients with 15 to 30 mm (median 20) renal cell carcinoma were included in the study and were treated with nephron sparing surgery. Median operative time was 110 minutes (range 60 to 150). Blood loss was less than 200 ml in each case. All tumors were pT1aN0M0 with negative margins. No postoperative complications were observed (hemorrhage, urinary fistulas, renal failure). Preoperative immunosuppressive treatment was not modified postoperatively. At 3 months after nephron sparing surgery and at a mean of 17.4 months of followup (range 5 to 54) no significant impairment of renal function or recurrence was observed. Nephron sparing surgery is a safe and efficient procedure for the treatment of renal cell carcinoma in renal grafts, resulting in the preservation of renal function and in short-term cancer control.


Analysis of slow- and fast-α band asymmetry during performance of a saccadic eye movement task: dissociation between memory- and attention-driven systems.
This study aimed at analyzing the relationship between slow- and fast-alpha asymmetry within frontal cortex and the planning, execution and voluntary control of saccadic eye movements (SEM), and quantitative electroencephalography (qEEG) was recorded using a 20-channel EEG system in 12 healthy participants performing a fixed (i.e., memory-driven) and a random SEM (i.e., stimulus-driven) condition. We find main effects for SEM condition in slow- and fast-alpha asymmetry at electrodes F3-F4, which are located over premotor cortex, specifically a negative asymmetry between conditions. When analyzing electrodes F7-F8, which are located over prefrontal cortex, we found a main effect for condition in slow-alpha asymmetry, particularly a positive asymmetry between conditions. In conclusion, the present approach supports the association of slow- and fast-alpha bands with the planning and preparation of SEM, and the specific role of these sub-bands for both, the attention network and the coordination and integration of sensory information with a (oculo)-motor response.


Eosinophil counts can be a predictive marker of immune checkpoint inhibitor-induced secondary adrenal insufficiency: a retrospective cohort study.
Immune checkpoint inhibitors (ICIs) treatment can result in endocrine immune-related adverse events (irAEs), including pituitary dysfunction. Quick diagnosis of secondary adrenal insufficiency (AI) is challenging because no universal definition of ICI-induced secondary AI has been agreed. The aim of this study was to clarify the clinical features of ICI-induced secondary AI that can be used for screening in standard clinical practice. This retrospective study was performed using the medical records of patients who received ICIs at Hirosaki University Hospital between 1 September 2014 and 31 January 2021. Longitudinal clinical data of patients who developed AI were analyzed and compared with the data of thyroid irAEs. Regression analysis showed a significant correlation between ICI-induced secondary AI and absolute or relative eosinophil counts at pre-onset of AI, as well as differences or rate of increase in eosinophil counts at baseline and at pre-onset. Absolute eosinophil counts > 198.36/µL or relative eosinophil counts > 5.6% at pre-onset, and a difference of 65.25/µL or a rate of eosinophil count increase of 1.97 between the baseline and at pre-onset showed the best sensitivity and specificity. This is the first report to demonstrate that eosinophil counts can be a predictor of ICI-induced secondary AI.


Return to Sports Activity following UKA and TKA.
Unicompartmental medial knee arthritis can be successfully treated with either unicompartmental or total knee arthroplasty (UKA or TKA). Active patients often inquire about the relative likelihood of returning to a sport-related activity after surgery. Some advocates of UKA suggest that UKA can lead to a higher rate of return to sports activity postoperatively, but little information is available comparing the outcomes of UKA versus TKA. We identified 33 patients with UKA and 39 patients with TKA with minimum 2-year follow-up (4 ± 1.2 years) who had similar preoperative clinical and radiographic examinations. Clinical evaluation revealed no difference in the number of patients who returned to sports or their satisfaction, but patients with UKA returned to sports more quickly and exhibited better postoperative knee scores than TKA patients.


Immune Modulation in the Treatment of Amyotrophic Lateral Sclerosis: A Review of Clinical Trials.
Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease characterized by the degeneration of motor neurons. Though many molecular and genetic causes are thought to serve as predisposing or disease propagating factors, the underlying pathogenesis of the disease is not known. Recent discoveries have demonstrated the presence of inflammation propagating substrates in the central nervous system of patients afflicted with ALS. Over the past decade, this hypothesis has incited an effort to better understand the role of the immune system in ALS and has led to the trial of several potential immune-modulating therapies. Here, we briefly review advances in the role of such therapies. The clinical trials discussed here are currently ongoing or have been concluded at the time of writing.


SIRT6 Promotes the Progression of Prostate Cancer via Regulating the Wnt/β-Catenin Signaling Pathway.
Sirtuin 6 (SIRT6), a DNA repair-related gene, has undergone an extremely thorough study for its involvement in the development of many different cancers. The objective of our study was to explore the function and mechanism of SIRT6-induced regulation of prostate cancer (PCa). RT-PCR was performed to validate the levels of SIRT6 in PCa cell lines. Cell proliferation, migration, and invasion of cells with SIRT6 knockdown were assessed using CCK-8 assay, colony formation assay, wound-healing assay, and transwell assay. Western blot was applied to assess the related proteins. We found that SIRT6 expression was distinctly upregulated in PCa specimens and cells. Loss-of-functional assays revealed that SIRT6 silence suppressed the proliferation and metastasis of PCa cells. Mechanistic studies revealed that SIRT6 silence inhibited Wnt/β-catenin signaling and EMT progress. Overall, the study confirmed the upregulation of SIRT6 in patients with PCa and its association with the progression. SIRT6 promoted PCa progression by regulating Wnt/β-catenin signaling, providing a promising biomarker and treatment approach for preventing PCa.


Characterization of the novel Sezary lymphoma cell line BKP1.
Cutaneous T-cell lymphomas (CTCL) are a heterogeneous group of lymphomas primarily involving the skin. The most common types are mycosis fungoides (MF) and Sezary Syndrome (SS). We report a novel long-term fast-growing SS line termed BKP1 that was characterized by flow cytometry (FC), conventional and molecular cytogenetic [FISH/multi-FISH together with array comparative genomic hybridization (aCGH)]. FC immunophenotype of the BKP1 is CD2+CD5+CD3+CD4+CD8-CD7-CD25-CD26-CD30-CD158k+. The TCRγ characterization of BKP1 by PCR identified a clonal rearrangement. The conventional cytogenetic and Multi-FISH analysis showed complex chromosomal rearrangements. aCGH analysis highlighted the loss of genes involved in cell cycle control, in immune response (HLA, complement complex) and DNA damage repair mechanisms. The BKP1 is another lymphoma cell line thoroughly characterized that can be a valuable tool for both basic and applied research such as identification of deregulated genes and/or pathways and screening for new antilymphoma drugs.


Communication: Manipulating the singlet-triplet equilibrium in organic biradical materials.
We investigated the tunability of the singlet-triplet equilibrium population in the organic biradical 1,4-phenylenedinitrene via magneto-optical spectroscopy. A rich magnetochromic response occurs because applied field increases the concentration of the triplet state species, which has a unique optical signature by comparison with the singlet biradical and the precursor molecule. A Curie-like analysis of the magneto-optical properties allows us to extract the spin gap, which is smaller than previously supposed. These measurements establish the value of local-probe photophysical techniques for magnetic property determination in open-shell systems such as biradicals where a traditional electron paramagnetic resonance Curie law analysis has intrinsic limitations.


Modulation of cisplatin chronotoxicity related to reduced glutathione in mice.
Intracellular reduced glutathione (GSH) concentrations were measured according to the tissue sampling-time along the 24 h scale in male B6D2F1 mice. A significant circadian rhythm in GSH content was statistically validated in liver, jejunum, colon and bone-marrow (P < or = 0.02) but not in kidney. Tissue GSH concentration increased in the dark-activity span and decreased in the light-rest span of mice. The minimum and maximum of tissue GSH content corresponded respectively to the maximum and minimum of cisplatin (CDDP) toxicity. The role of GSH rhythms with regard to CDDP toxicity was investigated, using a specific inhibitor of GSH biosynthesis, buthionine sulfoximine (BSO). Its effects were assessed on both tissue GSH levels and CDDP toxicity at three circadian times. BSO resulted in a 10-fold decrease of the 24 h-mean GSH in kidney. However a moderate GSH decrease characterized liver (-23%) and jejunum (-30%). BSO pretreatment largely enhanced CDDP toxicity which varied according to a circadian rhythm. Although BSO partly and/or totally abolished the tissue GSH rhythms, it did not modify those in CDDP toxicity. We conclude that GSH have an important influence on CDDP toxicity but not in the circadian mechanism of such platinum chronotoxicity.


Immunobiochemical status of sheep exposed to periods of experimental protein deficit and realimentation.
Immunobiochemical status of sheep exposed to periods of experimental protein deficit and realimentation was studied in 12 sheep (15 mo) randomly distributed into 2 equal groups and fed individually 2 different concentrate supplements along with wheat straw to provide 100% (normal protein, NP) or 50% (low protein, LP) of CP requirements. The study was comprised of 3 periods; during period 1 (0 to 13 wk) and 2 (14 to 26 wk) animals in the 2 groups were fed NP and LP diets, respectively; during period 3 (27 to 44 wk), animals in the LP group were switched over to NP diet to allow realimentation, whereas animals in the NP group remained on the same NP diet. Blood was collected from all groups at end of each period, and serum glucose, total protein, albumin (sAlb), globulin (sGlb), urea (sU), creatinine (sCr), cholesterol, triiodothyronine, and thyroxine concentrations were determined. During the same periods, the cell-mediated immune (CMI) response was measured by a delayed type hypersensitivity (DTH) assay and in vitro nitrite production by lymphocytes. At the end of periods 2 and 3, humoral immune response (HIR) was measured by sensitizing the sheep with Brucella abortus S99 antigen and measuring antibody titers on 0, 7, 14, 21, and 28 d postinoculation by ELISA. Feed intake decreased with prolonged protein deficit and showed recovery during period 3. Blood chemistry revealed reduced sAlb concentration in the LP group resulting in narrow sAlb:sGlb ratio, increased sCr concentrations (P = 0.008) accompanying a decreased (P = 0.004) sU:sCr ratio, and decreased glucose concentrations (P = 0.05). Other variables did not change significantly between the NP and LP groups. The DTH response at the end of period 1 and 2 showed marked (P = 0.008) effect of protein restriction on CMI. Nitrite production, basal and after lipopolysaccharide stimulation, was greater (P = 0.04) in the NP group. The HIR was less (P = 0.04) in the LP group during period 3. Realimentation of protein in the LP group during period 3 showed recovery in CMI and HIR. In conclusion, protein deprivation induced a decline in CMI and HIR in sheep accompanying alterations in related metabolic profile. However, a marked recovery was observed after realimentation.


Lung Deposition of Inhaled Extrafine Beclomethasone Dipropionate/Formoterol Fumarate/Glycopyrronium Bromide in Healthy Volunteers and Asthma: The STORM Study.
Background: An extrafine formulation triple therapy combination of beclomethasone dipropionate (BDP), formoterol fumarate (FF), and glycopyrronium bromide (GB) has been developed for the maintenance treatment of asthma and chronic obstructive pulmonary disease. This study used gamma scintigraphy to evaluate the intrapulmonary and extrapulmonary in vivo deposition of BDP/FF/GB, and the intrapulmonary regional distribution of the deposited formulation. Methods: This open-label uncontrolled nonrandomized single-dose study recruited 10 healthy volunteers and 9 patients with asthma. After a krypton-81m (81mKr) ventilation scan was conducted, subjects inhaled study drug (four inhalations of BDP/FF/GB 100/6/12.5 μg radiolabeled using technetium-99 m [99mTc]) through pressurized metered-dose inhaler, and a series of scintigraphic images were taken. The primary objective was to evaluate intrapulmonary drug deposition of BDP/FF/GB, determined as the percentage of nominal (i.e., metered) dose. Secondary endpoints included central/peripheral deposition ratio (C/P), and the standardized central/peripheral ratio (sC/P; 99mTc aerosol C/P/81mKr gas C/P). Results: All participants completed the study, with all scintigraphy procedures performed at one site. In patients with asthma, mean ± standard deviation intrapulmonary deposition was 25.50% ± 6.81%, not significantly different to that in healthy volunteers (22.74% ± 9.19%; p = 0.4715). Approximately half of the lung dose was deposited in the peripheral region of the lung (fraction deposited 0.52 ± 0.07 and 0.49 ± 0.06 in healthy volunteers and patients with asthma, respectively), resulting in C/P ratios of 0.94 ± 0.25 and 1.06 ± 0.25, respectively, with sC/P ratios of 1.80 ± 0.40 and 1.94 ± 0.38. Deposition patterns were similar in the two populations. BDP/FF/GB was well tolerated. Conclusions: This study confirmed that the extrafine particles delivered by BDP/FF/GB penetrate the peripheral areas of the lungs, with a similar proportion of particles deposited in the central and peripheral regions. Importantly, the deposition patterns were similar in healthy volunteers and patients with asthma, suggesting that disease characteristics are unlikely to impact drug deposition. Clinical Trial Registration number: NCT03795350.


Contractile function of aortic smooth muscle in guinea pig endotoxin shock.
Contractile responsiveness of aortic rings from control and endotoxin-shocked guinea pigs was examined in vitro. Aortae were removed 16 h following intraperitoneal administration of 4 mg/kg of Escherichia coli endotoxin or sterile saline. Although no shift in the dose-response curve or maximal contraction to norepinephrine (10(-9)-10(-4) M) was observed, there was an enhanced contractile response to KCl in shock rings. Calcium dose-response curves in both 60 mM and normal (5.4 mM) KCl were shifted upward in shock rings. This upward shift was abolished in normal KCl in the presence of the Ca2+ blocker D 600 (50 microM), suggesting enhanced Ca2+ influx via voltage-dependent Ca2+ channels in shock vascular smooth muscle. A deleterious effect of high cytoplasmic Ca2+ on vascular smooth muscle mitochondrial function may play a role in endotoxin shock.


Acute urinary retention caused by a large peritoneal inclusion cyst: a case report.
Pelvic masses have been known to cause bladder symptoms and compression. This is the first documented case of a large peritoneal inclusion cyst causing acute urinary retention from bladder outlet obstruction. A 36-year-old woman, gravida 2, para 2, presented to the gynecology clinic with an indwelling Foley catheter that was placed at an outside hospital secondary to acute urinary retention. Computed tomography, performed several days earlier for complaints of progressively worsening lower abdominal and pelvic pain, revealed a 10-cm, complex, cystic mass within the pelvis between the rectum and sigmoid colon, with anterior displacement of the bladder. The patient's past surgical history included a total abdominal hysterectomy as well as separate exploratory laparotomy for resection of a 20-cm peritoneal inclusion cyst and a prophylactic bilateral salpingo-oophorectomy. Due to the acute urinary retention and worsening pain, the decision was made to proceed with laparoscopic removal and drainage of the mass, which turned out to be consistent with a recurrent peritoneal inclusion cyst. Symptom relief was immediate. A large, recurrent, peritoneal inclusion cyst obstructed the bladder neck and presented as acute urinary retention. Laparoscopy relieved the symptoms.


Open-ended attributions for the performance of the elderly.
The present study explored open-ended attributions for the success and failure of relatively younger and older men in social and academic situations using a between-subjects design. Attributions were collected from 109 college students and were coded using the Elig and Frieze scheme. Results showed that respondents were more likely to make attributions that combined age with other attributional categories (age-related attributions) than attributions solely to target's age. And, they made more ability-task interaction than ability attributions. Moreover, both attributions were as likely to be made for the elderly adult's success as his failure. Finally, differences also emerged in results from the stability dimension and those for age-related and ability-task attributions indicating that these parameters should be assessed independently in future research.


Quality of Life of People with HIV/AIDS in Iran: A Systematic Review and Meta-Analysis.
Assessing the quality of life in HIV/AIDS patients is of great importance not only for evaluating the effect of the disease, but also to measure the impact of the interventions in order to improve their quality of life in clinical researches. Therefore, this study aimed to systematically review the quality of life of HIV/AIDS patients in Iran. In this systematic review and meta-analysis, the literature search using the related chain of keywords was conducted from 1 Jan 1987 to 30 Apr 2019 in PubMed, Scopus, Web of Science, Embase, Iranian Scientific Information Database (SID), and Magiran. Moreover, hand search of the key journals and the gray literature was performed. The meta-analysis was performed by CMA2 software. Out of the 1576 retrieved records, eight studies met the inclusion criteria. The average age of the patients was 37.15 ± 9.46 years. The average score of quality of life before and after sensitivity analysis was (39.13 [28.36-49.901 95% CI P>0.000] vs. 49.05 [46.31-51.79 95% CI P>0.000]). Moreover, the average score of quality of life was respectively 38.86±3.83 vs. 40±6.37 among married compared with single patients, 56.33±4.67 vs. 43.64±1.94 for employment vs. unemployment status. While quality of life was measured in terms of education level, the score was 29.59±9.34 vs. 41.65±4.45 in the individuals with primary school versus academic education. The QOL score of the HIV/AIDS patients in Iran was significantly low. Therefore, the study highlights the importance of strengthening efforts to undertake necessary investigations in order to provide adequate health insurance, extensive and affordable welfare services, and more appropriate social and mental supports in order to improve the quality of life of the individuals with HIV/AIDS in Iran.


Acetylcholinesterases of the cat flea Ctenocephalides felis: identification of two distinct genes and biochemical characterization of recombinant and in vivo enzyme activities.
Acetylcholinesterase (AChE, EC126.96.36.199.) is a prime target for insecticides and is the site of action of carbamate and organophosphate drugs used to combat the cat flea Ctenocephalides felis. In this paper we report the identification and cDNA cloning of two AChE-encoding genes from the cat flea, cface1 and cface2. Functional heterologous expression of the catalytic domains in Pichia pastoris shows that both genes encode functional enzymes, CfAChE1 and CfAChE2. Bioinformatical analysis of the predicted translation products and heterologous expression of the full length cDNAs in the human cell line HEK293 demonstrate, that CfAChE1 and CfAChE2 possess glycosylphosphatidylinositol membrane anchors and are transported to the cell surface. Recombinant CfAChE1 and CfAChE2 share high sensitivity towards the anti-flea carbamates propoxur and carbaryl, but can be distinguished by their specificity for different acylthiocholine AChE substrates and, particularly, by their differential sensitivity to the non-covalent inhibitor galanthamine. Comparison of substrate specificities and inhibitor sensitivities of both recombinant enzymes with those of AChE activities extracted from adult fleas suggest that CfAChE1, and not CfAChE2, is the dominant activity in C. felis imagoes. Three-dimensional structure models of CfAChE1 and CfAChE2 reveal similarities, but also differences, and compound docking experiments on these models provide potential rationales for the differential substrate and the inhibitor specificities observed experimentally.


An introduction to body vandalism: What is it? Who does it? When does it happen?
A number of typical consequences for alcohol and other substances have been well documented. However, a specific category of consequences which has received no attention in the existing literature includes acts (other than sexual assault) committed upon incapacitated individuals. We have termed this behavior body vandalism (BV), defined as the direct manipulation of an incapacitated individual through the addition of markings, objects or substances, removal of property or hair, or relocation of a body. The purpose of this paper is to provide a preliminary examination of rates of experiencing and variations in positive and negative perceptions of this behavior from the victim's perspective. A pilot study was conducted aimed at examining the rates and demographic characteristics of body vandalism in a national sample of 981 adults. The majority of individuals had witnessed BV, half had perpetrated, and over 40% had been a victim in their lifetime. Rates of lifetime victimization and perpetration were low (1-2 times). Perpetrators most often targeted their friends and alcohol was typically a factor in victimization. Over half of victims reported experiencing positive social outcomes as a result of being victimized and about a third reported negative emotional outcomes. Findings suggest that experiences of body vandalism are relatively common, especially in young adults, associated with alcohol consumption, and result in both positive and negative outcomes for victims. This study offers evidence for BV as an outcome of social drinking, suggests contexts that increase the risk of BV occurrence, and provides a foundation from which future studies can build.


Insights on the HLA-Binding Peptidome in Cancer.
The intracellular compartments for proteolytic antigen processing in tumor cells produce peptides that are presented by MHC molecules to T cells. But first, the ubiquitin ligase system tags defective, misfolded, aged, and unstable proteins for degradation through the proteasome. Ubiqitinated proteins are unfolded and fed into the barrel-shaped core of the proteasome where a collection of multiple different proteases cleave proteins into oligopeptides. After exiting the proteasome, these oligopeptides are either completely degraded into amino acids or trimmed at the N- and C-termini so that they bind to transporter associated with antigen processing (TAP). TAP translocates oligopeptides into the ER where they are further trimmed and may bind to MHC molecules. Resulting peptide-MHC complexes then travel to the cell surface for T cell recognition. Many defects or anomalies in the proteolytic processing of tumor-derived proteins may suppress the expression of peptide-MHC complexes, which plays a role in escape of tumors from the immune system. However, due to the general dysregulated intracellular machinery of tumors, many proteins are translated from unconventional RNA transcripts including noncoding RNA, exon-intron retentions, and alternative splicing. These products of translation can serve as novel peptides for T cells as they recognize and kill tumors.


Differential impact of cilostazol on restenosis according to implanted stent type (from a pooled analysis of three DECLARE randomized trials).
Even in the drug-eluting stent era, restenosis has remained an unresolved issue, particularly in the treatment of complex coronary lesions. In this study, patient-level data from 3 randomized trials (Drug-Eluting Stenting Followed by Cilostazol Treatment Reduces Late Restenosis in Patients With Diabetes Mellitus [DECLARE-DIABETES] and Drug-Eluting Stenting Followed by Cilostazol Treatment Reduces Late Restenosis in Patients With Long Native Coronary Lesions [DECLARE-LONG] I and II) were pooled to estimate the differential antirestenotic efficacy of add-on cilostazol according to the implanted drug-eluting stent in patients at high risk for restenosis. A total of 1,399 patients underwent sirolimus-eluting stent (SES; n = 450), paclitaxel-eluting stent (n = 450), and zotarolimus-eluting stent (n = 499) implantation and received triple-antiplatelet therapy (TAT; aspirin, clopidogrel, and cilostazol, n = 700) and dual-antiplatelet therapy (aspirin and clopidogrel, n = 699). Randomization of antiplatelet regimen was stratified by stent type. In-stent late loss after TAT was significantly lower than that after dual-antiplatelet therapy, regardless of implanted stent type. However, the incidence of in-segment restenosis after TAT was significantly lower with SES (0.5% vs 6.7%, p = 0.014) and zotarolimus-eluting stent (12.2% vs 20.0%, p = 0.028) implantation but not paclitaxel-eluting stent implantation (14.4% vs 20.0%, p = 0.244). A significant interaction was present between stent type and antiplatelet regimen for the risk for in-segment restenosis (p = 0.004). Post hoc analysis using bootstrap resampling methods showed that the relative risk reduction for in-segment restenosis after TAT was most prominent with SES implantation. In conclusion, add-on cilostazol effectively reduced restenosis in patients at high risk for restenosis, particularly in those receiving SES, suggesting the sustainable utility of add-on cilostazol therapy in newer generation drug-eluting stents with comparable efficacy with that of SES.


A Facile Approach for Elemental-Doped Carbon Quantum Dots and Their Application for Efficient Photodetectors.
The present work demonstrates a facile hydrothermal approach to synthesize lanthanide-doped carbon quantum dots (CQDs) with europium and/or gadolinium elements. Taking the advantage of broadband adsorption in the ultraviolet-visible region, the doped QDs are directly used as building blocks for photo-electrochemical (PEC)-type photodetectors (PDs) and their performance is systematically investigated under various conditions. The europium (Eu) and gadolinium (Gd) co-doped (C:EuGd) QDs exhibit better photo-response than the single-elemental doped ones and also show outstanding long-term stability. According to the apparent response to light from 350 to 400 nm, the C:EuGd QDs are demonstrated to hold great potential for narrow-band PDs. This work highlights the practical applications of lanthanide-doped CQDs for PDs, and the results are beneficial for the development of elemental-doped CQDs in general.


Need for kidney transplantation in HIV-positive individuals: results of a survey in Italy.
It is well known that HIV+individuals can be affected by end-stage renal diseases (ESRD). Despite the availability of new effective antiretroviral therapies, HIV-infected people are generally excluded from kidney transplantation, the treatment of choice for ESRD. A small number of transplantations have been performed, with encouraging data in terms of graft and patient survival. To evaluate the need of kidney transplant for HIV+individuals, we designed a multicentre study which enabled the simulation of a virtual transplant waiting list for those on dialytic treatment. In 38 participating infectious disease units, 16 HIV+patients were selected for renal replacement treatment/dialytic treatment, and they were enrolled. Clinical data were collected in order to apply general exclusion criteria and evaluate HIV clinical status. Clinical data confirmed inclusion of 7/16 patients. After application of CD4+count and HIV viraemia for further selection, the number of subjects was significantly reduced. Six patients had CD4+count greater than 200/cmm (2/6 with undetectable HIV viraemia). Only 3 patients had CD4+higher than 350/cmm (1/3 with undetectable HIV viraemia). Our data represent the first evaluation of the need and eligibility for kidney transplantation for HIV+subjects with ESRD. Application of HIV infection related parameters as selection criteria has a great strength in reducing the waiting list of HIV+subjects suitable for kidney transplant and could be carefully considered when planning inclusion/exclusion criteria for experimental purposes.


Aberrant JAK/STAT Signaling Suppresses TFF1 and TFF2 through Epigenetic Silencing of GATA6 in Gastric Cancer.
Aberrant Janus kinase (JAK)/signal transducer and activator of transcription (STAT) signaling is crucial to the development of gastric cancer. In this study, we examined the role of STAT3 in the expression and methylation of its targets in gastric cancer patients. Results from RNA sequencing identified an inverse correlation between the expression of STAT3 and GATA6 in 23 pairs of gastric cancer patient samples. We discovered that the expression of GATA6 is epigenetically silenced through promoter methylation in gastric cancer cell lines. Interestingly, the inhibition of STAT3 using a novel STAT3 inhibitor restored the expression of GATA6 and its targets, trefoil factors 1 and 2 (TFF1/2). Moreover, disruption of STAT3 binding to GATA6 promoter by small hairpin RNA restored GATA6 expression in AGS cells. A clinically significant correlation was also observed between the expression of GATA6 and TFF1/2 among tissue samples from 60 gastric cancer patients. Finally, bisulfite pyrosequencing revealed GATA6 methylation in 65% (39/60) of the patients, and those with higher GATA6 methylation tended to have shorter overall survival. In conclusion, we demonstrated that aberrant JAK/STAT signaling suppresses TFF1/2 partially through the epigenetic silencing of GATA6. Therapeutic intervention of STAT3 in reversing the epigenetic status of GATA6 could benefit the treatment of gastric cancer and is worthy of further investigation.


[Mortality due to multiple sclerosis in Spain, 1951-1992].
FOUNDATIONS: In this work, multiple sclerosis mortality trend in Spain from 1951 to 1992 is displayed. The purpose is to identify the pattern of age-adjusted mortality evolution and to measure the effect of environmental factors. Multiple sclerosis mortality is standardized by age using the world standard population. In each year from 1951 to 1992, age-specific mortality rates are transversely fitted to the Gompertz law. The Longitudinal Gompertzian analysis is applied to the obtained coefficients to quantify the effects of competing risks and environmental factors. Multiple sclerosis age-adjusted mortality increased from 1951 to 1968; a step-down is produced in 1969 (coinciding with change from 7th to 8th revision of the International Classification of Diseases) and a stability from 1970 on. Multiple sclerosis in Spain is a Gompertzian disease. Adjusting mortality for R0 (which in the Gompertz function represents the addition of the environmental factors acting in a point near the beginning of the life and the competing risks of death) the result was almost constant throughout the whole analyzed period. It is suggested that multiple sclerosis mortality trend in Spain is due to changes in some environmental factor acting early and in a point; on the other hand, diet or other environmental factors acting for long time or genetic factors have and little or no influence in this trend.


The Prognostic Impact of Radiotherapy Delays in Oropharynx Carcinoma and the Role of p16 Status.
A retrospective analysis was performed to evaluate the prognostic significance of treatment delays (TDs) for oropharynx carcinoma patients treated with definitive radiotherapy (RT), comparing p16+ versus p16- disease. Patients treated between 2012 and 2016 were analyzed (n=763). TD was defined as the time from pathologic diagnosis to initiation of RT. TD thresholds of ≤60, 61 to 90, and >90 days were used to stratify outcomes. Time on treatment (TOT) delays were estimated based on the RT fractionation. TOT delay of 1 to 3 days was compared with >3 days. Predictors of cancer-specific survival (CSS) and locoregional recurrence (LRR) were evaluated on multivariable analysis. Six hundred fifty (85%) patients had p16+ disease. On multivariable analysis, TOT delay of 1 to 3 days versus <1 day was associated with inferior CSS (hazard ratio [HR]=1.81; 95% confidence interval [CI]: 1.02-3.22). TD >90 versus ≤60 days (HR=1.68; 95% CI: 0.98-3.04) and 61 to 90 versus ≤60 days (HR=0.94; 95% CI: 0.60-1.48) was not associated with CSS. TD >90 versus ≤60 days (HR=1.29; 95% CI: 0.66-2.52), TD 61 to 90 versus ≤60 days (HR=0.98; 95% CI: 0.64-1.52), TOT 1 to 3 versus <1 day (HR=0.91; 95% CI: 0.39-2.11), and TOT >3 versus <1 day (HR=1.79; 95% CI: 0.80-3.99) were not associated with LRR. There was no interaction between p16 status and TD in relation to LRR (P=0.27) or CSS (P=0.17). TDs were not significantly associated with CSS or LRR. TOT of 1 to 3 days was associated with inferior CSS. p16 status should not be a significant factor when triaging RT start dates.


A Case of Coil Embolization for a Ruptured Anterior Spinal Artery Aneurysm Associated with Bilateral Vertebral Artery Occlusion.
Anterior spinal artery (ASA) aneurysms are rare, and the majority are associated with vascular lesions such as arteriovenous malformations, moyamoya disease, and aortic stenosis. Herein, we report a case of a ruptured anterior spinal artery aneurysm caused by bilateral vertebral artery (VA) occlusion, which was treated by coil embolization. An 83-year-old man was found collapsed at home, and was brought in by emergency. His consciousness level was I-1 on the Japan Coma Scale, and there were no symptoms such as paralysis in the extremities. Computed tomography showed Fisher 3 subarachnoid hemorrhage, while magnetic resonance angiography showed an aneurysm in the right VA. Digital subtraction angiography showed bilateral VA occlusion, and an aneurysm was found on the dilated ASA as a collateral circulation. Coil embolization was performed after confirmation of no hemodynamic problems. No postoperative adverse events were observed. Coil embolization may be an effective treatment for ruptured aneurysms of the ASA.


[MRSA as a challenge to clinical organization].
Epidemics, caused by methicillin-resistant Staphylococcus aureus (MRSA) are an increasing problem in surgical hospitals. About 10 years ago, Germany only had sporadic cases with MRSA; currently, about 15% of all Staphylococcus aureus in Germany are methicillin-resistant. The most important measures in management and therapeutic strategies regarding MRSA are presented.


Effect of dielectric spacer thickness on signal intensity of surface plasmon field-enhanced fluorescence spectroscopy.
Surface plasmon field-enhanced fluorescence spectroscopy (SPFS) combines enhanced field platform and fluorescence detection. Its advantages are the strong intensity of the electromagnetic field and the high signal/noise (S/N) ratio due to the localized evanescent field at the water/metal interface. However, the energy transfer from the fluorophore to the metal surface diminishes the fluorescence intensity, and this reduces the sensitivity. In this study, we tested whether polystyrene (PSt) could act as a dielectric layer to suppress the energy transfer from the fluorophore to the metal surface. We hypothesized that this would improve the sensitivity of SPFS-based immunoassays. We used α-fetoprotein (AFP) as a model tumor biomarker in the sandwich-type immunoassay. We determined the relationship between fluorescent signal intensity and PSt layer thickness and compared this to theoretical predictions. We found that the fluorescence signal increased by optimally controlling the thickness of the PSt layer. Our results indicated that the SPFS-based immunoassay is a promising clinical diagnostic tool for quantitatively determining the concentrations of low-level biomarkers in blood samples.


Scalp reconstruction with a prefabricated abdominal flap carried by the radial artery.
Custom prefabrication of free flaps provides an unlimited variety of applications, since flaps can be created with expendable tissues and without restriction to naturally occurring vascular territories. These principles also can be used to customize flaps that could not be completed by conventional means. We report a case of scalp reconstruction using a random-pattern abdominal flap in which a radial artery fascial flap was induced to serve as the vascular carrier. In addition to providing durable scalp coverage, the prefabricated free flap enabled salvage of an abdominal flap that would otherwise have been aborted after intermediate transfer to the forearm.


Ketoconazole increases cocaine and opioid use in methadone maintained patients.
Stress plays an important role in substance abuse problems. For example, in studies with rodents stress induces reinstatement of opioid and cocaine self-administration. In addition, attenuation of the stress response by pharmacological adrenalectomy using ketoconazole, a cortisol synthesis inhibitor, reduces cocaine self-administration in rodents. In contrast, studies in primates and humans have produced conflicting results using cortisol synthesis inhibitors for attenuating cocaine-related behaviors and subjective effects. To explore the treatment implications of these findings, ketoconazole's (600-900 mg daily) ability to reduce heroin and cocaine use was compared with placebo in 39 methadone maintained patients with a history of cocaine abuse or dependence during a 12-week double blind trial. Contrary to the predicted effects, both heroin and cocaine use increased after patients were stabilized on methadone and ketoconazole. Depressive and withdrawal symptoms improved no more with ketoconazole than with placebo treatment, and side effects were greater on ketoconazole than placebo. As reported before with methadone treatment, morning cortisol levels were significantly lower than normal values throughout the clinical trial, but were not lower with ketoconazole than placebo treatment. Thus, in agreement with the negative results from acute dosing studies in primates and humans, chronic ketoconazole treatment does not appear to reduce cocaine or opioid use in humans maintained on methadone.


Sequence complexity effects on speech production in healthy speakers and speakers with hypokinetic or ataxic dysarthria.
The present study investigated the effects of sequence complexity, defined in terms of phonemic similarity and phonotoactic probability, on the timing and accuracy of serial ordering for speech production in healthy speakers and speakers with either hypokinetic or ataxic dysarthria. Sequences were comprised of strings of consonant-vowel (CV) syllables with each syllable containing the same vowel, /a/, paired with a different consonant. High complexity sequences contained phonemically similar consonants, and sounds and syllables that had low phonotactic probabilities; low complexity sequences contained phonemically dissimilar consonants and high probability sounds and syllables. Sequence complexity effects were evaluated by analyzing speech error rates and within-syllable vowel and pause durations. This analysis revealed that speech error rates were significantly higher and speech duration measures were significantly longer during production of high complexity sequences than during production of low complexity sequences. Although speakers with dysarthria produced longer overall speech durations than healthy speakers, the effects of sequence complexity on error rates and speech durations were comparable across all groups. These findings indicate that the duration and accuracy of processes for selecting items in a speech sequence is influenced by their phonemic similarity and/or phonotactic probability. Moreover, this robust complexity effect is present even in speakers with damage to subcortical circuits involved in serial control for speech.


University population-based prospective cohort study of SARS-CoV-2 infection and immunity (SARSSURV-ULiège): a study protocol.
For a safe and sustainable return to normal functioning of academic activities in higher education, objective-driven testing strategies that are flexible and rapidly adaptable are essential to effectively monitor and respond to new developments of the COVID-19 pandemic. To date, prospective longitudinal research on SARS-CoV-2 antibody testing in saliva and seroprevalence in higher education contexts is substantially lacking, limiting our understanding of COVID-19 prevalence, incidence and nature of the immune response to SARS-CoV-2 at various stages of the infection and vaccination. To address this lack of evidence, a prospective population-based cohort study (SARSSURV-ULiège) has recently been started. Students (n=1396) and staff members (n=1143) of the University of Liège are followed up over more than 1 year. All participants are required to complete anamnestic, clinical and vaccine hesitancy questionnaires for medical histories and undertaken treatments. Previous proven or suspected SARS-CoV-2 infection is also registered. In phase 1, weekly saliva samples to perform RT-qPCR to detect SARS-CoV-2 and monthly COVID-19 serological rapid test results are collected. Once being positive to either saliva RT-qPCR assay for SARS-CoV-2 presence or to serological test, the participant is invited to enter phase 2. If participants get vaccinated during the study period, they are invited to phase 2. In this second phase, besides weekly saliva self-test, depending on the participants' profiles, both gargle and blood samples are collected to obtain various biological data to measure the presence of neutralising antibodies against SARS-CoV-2, determine the magnitude and the duration of antibody responses over time. The study has received the approval from the University Hospital of Liège Ethics Committee (reference number 2021/96, dated 26 March 2021). Potential protocol amendments will be presented to the Research Ethics Committee. The findings of the present study will be presented at scientific conferences and the results published in peer-review publications. Weekly reports will be submitted to the risk assessment group and the risk management group against COVID-19 of the university to enable a timely public health action if necessary.


Variability of the Prevalence of Depression in Function of Sociodemographic and Environmental Factors: Ecological Model.
Major depression etiopathogenesis is related to a wide variety of genetics, demographic and psychosocial factors, as well as to environmental factors. The objective of this study is to analyze sociodemographic and environmental variables that are related to the prevalence of depression through correlation analysis and to develop a regression model that explains the behavior of this disease from an ecological perspective. This is an ecological, retrospective, cross-sectional study. The target population was 1,148,430 individuals over the age of 16 who were registered in Aragon (Spain) during 2010, with electronic medical records in the community's primary health care centers. The spatial unit was the Basic Health Area (BHA). The dependent variable was the diagnosis of Depression and the ecological independent variables were: Demographic variables (gender and age), population distribution, typology of the entity, population structure by sex and age, by nationality, by education, by work, by salary, by marital status, structure of the household by number of members, and state of the buildings. The results show moderate and positive correlations with higher rates of depression in areas having a higher femininity index, higher population density, areas with a higher unemployment rate and higher average salary. The results of the linear regression show that aging +75 and rural entities act as protective factors for depression, while urban areas and deficient buildings act as risk factors. In conclusion, the ecological methodology may be a useful tool which, together with the statistical epidemiological analysis, can help in the political decision making process.


Carcinoma of the endometrium: do the nuclear grade and DNA ploidy provide more prognostic information than do the FIGO and WHO classifications?
The aim of this study was to compare the World Health Organization (WHO), the International Federation of Gynecology (FIGO), and nuclear grading systems and to evaluate their reproducibility, as well as their prognostic impact, in relation to clinical variables and DNA ploidy. The study comprised 266 women with endometrial carcinoma in clinical stages I-IV. Low-risk patients, i.e., patients with grade 1-2 tumors in clinical stage I, were generally not included. In univariate Cox analyses, WHO, FIGO, and especially nuclear grading (p < 0.001), as well as age, stage, and ploidy, were prognostic regarding survival. In the multivariate Cox analyses, WHO and FIGO grades yielded little further independent information beyond nuclear grade. When DNA ploidy was added to the analyses, nuclear grade lost most of its impact because aneuploidy was a powerful factor (p < 0.001) that covaried with nuclear grade. The WHO, FIGO, and nuclear grading systems were found to be subjective, with correlation coefficients of approximately 0.60 between different pathologists. Age, stage, and aneuploidy were the most important predictors of outcome in the multivariate analyses. Nuclear grade was a strong prognostic factor in the univariate analyses and a more important indicator than the commonly used histopathological grading systems.


Phylogenetic relationships among the microgastroid wasps (Hymenoptera: braconidae): combined analysis of 16S and 28S rDNA genes and morphological data.
Relationships among the microgastroid complex of braconid wasps were investigated using sequence data from the 16S mitochondrial rDNA and 28S (D2 expansion region) nuclear rDNA genes, as well as morphological data. Parsimony analysis of these gene fragments, both separately and combined, indicated that Neoneurus (Neoneurinae) and Ichneutes (Ichneutinae) were no more closely related to the microgastroids than were a range of helconoid taxa. Combined parsimony analysis of the microgastroids indicated the relationships ((Cardiochilinae + Microgastrinae) + Miracinae) + Cheloninae, with Adeliinae falling inside the Cheloninae. Bootstrap proportions for each of these nodes were greater than 70%. Character reweighting (sensu Farris), using the rescaled consistency index, also recovered these relationships. Mapping of lifestyle traits onto this relatively well supported phylogeny indicated that solitary endoparasitism is ancestral for the microgastroids, with a single origin for egg-larval endoparasitism in the Cheloninae + Adeliinae. Mapping of the radiation of the microgastroids into lepidopteran hosts was less clear, due to the specialized biology of the most basal microgastroid clade, the Cheloninae + Adeliinae. Our data are consistent with attack of concealed lepidopteran hosts as the plesiomorphic lifestyle, at least for the Miracinae + Cardiochilinae + Microgastrinae, with radiation into more exposed hosts in the Cardiochilinae + Microgastrinae.


Desipramine blocks stress-induced prolactin release in rats: role of central beta-2 adrenoceptors.
1. The present study was designed to examine the relationship between beta-adrenoceptors and the enhanced, sustained prolactin secretion induced by immobilization stress in rats. 2. Chronic administration of desipramine (15 mg kg-1 day-1, intraperitoneally) for 7 days, a procedure that desensitizes central beta-adrenoceptors, partially inhibits stress-induced prolactin release. 3. Intracerebroventricular administration of the beta-2 adrenoceptor agonist salbutamol (1 microgram/rat) to rats pretreated with desipramine for 7 days, 15 min before immobilization, significantly relieved the inhibition by desipramine 5 and 10 min after the initiation of stress but the effect was not demonstrable after 20 and 40 min. 4. We conclude that beta-2 adrenoceptors play a role in the control of prolactin release in response to stress.


[The treatment of genu recurvatum (author's transl)].
50 cases of genu recurvatum were classified into three types: osseous (malunion, epiphysiodesis), capsular and ligamentous (congenital hyper-extension, sequelae of old ligament rupture) and combination of the two types. The author's have analysed the results of 44 surgical procedures. The main procedure practised has been an opening wedge osteotomy of the upper end of the tibia above the level of the tibial tubercle with a graft to fill the gap. It is important to avoid distal displacement of the patella by detachment of the tibial tubercle and reattachment more proximally at the end of the surgical procedure. Osteotomy is always indicated but should be combined with a capsular repair or combined types. The results are satisfactory especially in cases due to premature closure of the growth plate.


To what extent are soil amendments useful to control Verticillium wilt?
The genus Verticillium includes several species that attack economically important crops throughout the world. The control of Verticillium spp. becomes especially difficult when they form microsclerotia that can survive in the field soil for several years. It has been common practice to fumigate soil with chemicals such as methyl bromide and/or chloropicrin to control soil-borne fungal pathogens. Other chemicals that are used against Verticillium spp. are the antifungal antibiotic aureofungin, the fungicides benomyl, captan, carbendazim, thiram, azoxystrobin and trifloxystrobin and the plant defence activator acibenzolar-S-methyl. However, the potential risks involved in applying phytochemicals to crop plants for both the environment and human health, together with their limited efficacy for controlling Verticillium-induced diseases, support the need to find alternatives to replace their use or improve their efficacy. Soil amendment with animal or plant organic debris is a cultural practice that has long been used to control Verticillium spp. However, today the organic farming industry is becoming a significant player in the global agricultural production scene. In this review, some of the main results concerning the efficacy of several soil amendments as plant protectors against Verticillium spp. are covered, and the limitations and future perspectives of such products are discussed in terms of the control of plant diseases.


Parallel compressive sensing in a hybrid space: Application in interventional MRI.
Recently, susceptibility based positive contrast MRI technique emerged as an effective method of visualizing the small MR compatible devices, such as brachytherapy seeds. One of the challenges associated with this method is the long scan time. In this work, we present an accelerated susceptibility based positive contrast MR imaging method, in which the susceptibility map can be generated from an under-sampled data. We use a combination of parallel imaging (GRAPPA) and compressive sensing (CS) technique in a hybrid k-space. The results in brachytherapy seeds imaging show that 3-D high-quality images can be achieved at an acceleration factor up to 4, which can decrease the scan time from 4 minutes to 1.4 minutes.


Fatigue Resistance Is Altered during the High-Hormone Phase of Eumenorrheic Females but Not Oral Contraceptive Users.
This study aimed to examine the effect of ovarian hormones and their synthetic equivalents on substrate utilization and fatigue resistance during a race-specific cycling protocol. Seventeen well-trained female cyclists (nine eumenorrheic females, eight oral contraceptive users) completed two experimental trials, in a randomized order, in their low- (follicular/sugar pill) and high-hormone (luteal/active pill) phases. Each 91-min trial consisted of a 45-min moderate-intensity component (submaximal cycling, or SMC) followed by 6 min of high-intensity (HIT) and then a fatigue resistance test (FRT): 6 × 1-min all-out efforts with 1-min active recovery. Meals, comprising carbohydrate (CHO) intake of 8 g·kg -1 body mass, were standardized 24-h pretrial. An electrolyte-only solution was provided ad libitum during each trial. In eumenorrheic females, a large reduction in average power during FRT was observed in the luteal phase (277 ± 31 vs 287 ± 33 W; P = 0.032). Greater CHO ox (~ 4%, P = 0.020) during SMC and ventilatory inefficiencies during SMC and HIT (~7%, P < 0.001) were also observed in the luteal phase. In contraceptive users, despite some phasal changes in cardiorespiratory and metabolic data in SMC (~6% higher blood glucose and ~2% higher minute ventilation in active pill phase), none of the performance parameters in the FRT were different. Fatigue resistance was compromised only in high-hormone phase of the menstrual cycle, with eumenorrheic females likely susceptible because of increased CHO utilization during SMC. Hormone-induced ventilatory inefficiencies may also have increased metabolic demand. These findings emphasize the need to maintain CHO availability for power production, particularly in high-hormone phases.


Inhalant abuse in New Zealand.
To describe patterns of inhalant abuse in New Zealand and discuss management. Calls to the National Poisons Centre (NPC) from January 1 2003 to December 31 2004 were analysed. In addition, deaths following inhalational abuse were identified from the Institute of Environmental Science and Research Limited (ESR) database for 2001 and 2002 and available data for 2003. Seventy calls were classified as relating to inhalational abuse incidents. In abusers whose age was known, 83% were between 11 and 20 years, and 61% were male. Over half (44/70) of the calls involved abuse of propane or butane, either alone or in combination with a synthetic pyrethroid. ESR coronial data identified 11 inhalant abuse related deaths, most commonly attributed to cardiac effects. 73% of deaths were in teenagers and all but one fatality involved propane and/or butane. Inhalant abuse is a persisting problem in New Zealand. NPC and ESR data demonstrate that teenagers are more likely to abuse inhalants than other age groups and butane and propane are the inhalants of choice. Acute management can be difficult, with significant mortality and morbidity. Continued education and other preventive measures are essential to help curb an extremely dangerous practice.


Comparative analysis of landscape effects on spatial genetic structure of the big brown bat and one of its cimicid ectoparasites.
Identification of landscape features that correlate with genetic structure permits understanding of factors that may influence gene flow in a species. Comparing effects of the landscape on a parasite and host provides potential insights into parasite-host ecology. We compared fine-scale spatial genetic structure between big brown bats (Eptesicus fuscus) and their cimicid ectoparasite (Cimex adjunctus; class Insecta) in the lower Great Lakes region of the United States, in an area of about 160,000 km2. We genotyped 142 big brown bat and 55 C. adjunctus samples at eight and seven microsatellite loci, respectively, and inferred effects of various types of land cover on the genetic structure of each species. We found significant associations between several land cover types and genetic distance in both species, although different land cover types were influential in each. Our results suggest that even in a parasite that is almost entirely reliant on its hosts for dispersal, land cover can affect gene flow differently than in the hosts, depending on key ecological aspects of both species.


[Changes in the blood flow of the primary carotid and its branches during modifications of the O2 and CO2 composition of alveolar gas].
We measured common carotid blood flow using a range gated Doppler velocimeter, and internal and external blood velocities using a continuous Doppler in 20 lowlanders at sea level, under normal barometric pressure, in 10 subjects in an altitude chamber under a barometric pressure of 462 Torr (61.6 KPa) and then in 5 of them over a 3-weeks period at 3850 m of elevation (475 Torr = 63.3 KPa). The same measurements were also performed in 20 permanent residents at 3850 m. Common carotid blood flow was 15% higher in all subjects exposed to high altitude, due to a lowering in downstream resistances since systemic blood pressure did not change at high altitude. The increase in common carotid blood flow was the result of an immediate increase in internal carotid blood velocities observed in the altitude chamber as well as after the arrival at high altitude, but a few days later those velocities in the internal carotid artery declined to values similar to those observed at sea level. In the same time velocities in external carotid artery rose at high altitude, remained steadily elevated and the result is a permanent increase in common carotid blood flow at altitude. In all subjects we performed the same measurements, during an acute inhalation of gas mixtures to try to quantify the mechanisms controlling the changes in common carotid blood flow while changing gas inhalation. In the limits of the variations in PO2 (60 to 400 Torr) and in PCO2 (30 to 50 Torr) the stimulation by CO2 is twice more efficient than the O2 stimulation on vasomotion.


Direct glycosylation of unprotected and unactivated carbohydrates under mild conditions.
Ligand exchange acetalization of acetals in the presence of catalytic amounts of mandelic acid and titanium tert-butoxide is reported. This transformation is successfully extended to glycosylation of unprotected and unactivated pentoses. Even unreactive pentoses such as D-arabinose or D-lyxose can be transformed by this new methodology into corresponding isopropyl glycosides.


N-Acetylcysteine treatment of dystrophic mdx mice results in protein thiol modifications and inhibition of exercise induced myofibre necrosis.
Oxidative stress is implicated as a factor that increases necrosis of skeletal muscles in Duchenne Muscular Dystrophy (DMD) and the dystrophic mdx mouse. Consequently, drugs that minimize oxidative stress are potential treatments for muscular dystrophy. This study examined the in vivo benefits to mdx mice of an antioxidant treatment with the cysteine precursor N-acetylcysteine (NAC), administered in drinking water. NAC was completely effective in preventing treadmill exercise-induced myofibre necrosis (assessed histologically) and the increased blood creatine kinase levels (a measure of sarcolemma leakiness) following exercise were significantly lower in the NAC treated mice. While NAC had no effect on malondialdehyde level or protein carbonylation (two indicators of irreversible oxidative damage), treatment with NAC for one week significantly decreased the oxidation of glutathione and protein thiols, and enhanced muscle protein thiol content. These data provide in vivo evidence for protective benefits of NAC treatment on dystropathology, potentially via protein thiol modifications.


Tight association of loss of merlin expression with loss of heterozygosity at chromosome 22q in sporadic meningiomas.
Mutations of NF2, the gene for neurofibromatosis 2, are detected in 20-30% of sporadic meningiomas, and almost all mutations lead to loss of merlin expression. However, loss of heterozygosity (LOH) at chromosome 22q is found at a much higher frequency, up to 50-70%, and the possibility of another tumor suppressor gene in this region has not been excluded. Furthermore, a recent report proposed that abnormal activation of a protease micro-calpain can be an alternative pathway for merlin loss in meningiomas and schwannomas. To determine the correlation of merlin loss with NF2 genetic alteration or micro-calpain activation, we performed a molecular genetic analysis of 50 sporadic meningiomas and also examined the expression status of merlin and active form micro-calpain. LOH assay of five microsatellite markers franking NF2 revealed LOH in 22 cases, and single-strand conformation polymorphism assay detected six frameshift mutations, two splicing mutations, one nonsense mutation, and one missense mutation, all accompanied by 22q LOH. In addition, a multiplex PCR assay indicated homozygous deletion of NF2 in two cases. Interestingly, a marked decrease of merlin expression was seen exclusively in the 22 cases with 22q LOH. Activated micro-calpain expression was observed in 28 cases at various levels but showed no correlation with merlin status. These data strongly support the notion that NF2 is the sole target of 22q LOH in meningiomas and that loss of merlin expression is always caused by genetic alteration of NF2, following the classic "two hit" theory.


Determinants of urban-rural differences in cardiovascular risk factors in middle-aged women in India: a cross-sectional study.
Cardiovascular diseases (CVD) are the most important cause of death amongst middle-aged Indian women. To determine prevalence of CVD risk factors and their determinants we performed a nationwide study. Population based studies amongst women 35-70 years were performed in four urban and five rural locations in India. Location based stratified sampling was performed and we enrolled 4624 (rural 2616, urban 2008) of eligible 8000 women (58%). Demographic details, medical history, diet, physical activity and anthropometry were recorded using standardised techniques. Blood haemoglobin, glucose and total cholesterol were determined. Risk factors were diagnosed using current guidelines. Descriptive statistics are reported. Stepwise multivariate logistic regression was performed to identify determinants of urban-rural differences. In urban women mean body mass index (BMI), waist circumference, waist-hip ratio (WHR), systolic BP, haemoglobin, fasting glucose and cholesterol were significantly greater (p<0.01). Age-adjusted prevalence of risk factors (%) in urban vs rural was of obesity BMI ≥ 25 kg/m(2) (45.6 vs 22.5), truncal obesity WHR>0.9 (44.3 vs 13.0), hypertension (37.5 vs 29.3), hypercholesterolemia ≥ 200 mg/dl (27.7 vs 13.5), and diabetes (15.1 vs 4.3) greater whilst any tobacco use (19.6 vs 41.6) or smoking lower. Significant determinants of urban-rural differences were greater income and literacy, dietary fats, low physical activity, obesity and truncal obesity (p<0.01). Greater prevalence of CVD risk factors in urban middle-aged women is explained by greater income and literacy, dietary fat, low physical activity and obesity.


Photochemically engineering the metal-semiconductor interface for room-temperature transfer hydrogenation of nitroarenes with formic acid.
A mild photochemical approach was applied to construct highly coupled metal-semiconductor dyads, which were found to efficiently facilitate the hydrogenation of nitrobenzene. Aniline was produced in excellent yield (>99 %, TOF: 1183) using formic acid as hydrogen source and water as solvent at room temperature. This general and green catalytic process is applicable to a wide range of nitroarenes without the involvement of high-pressure gases or sacrificial additives.


The dose-response relation for the antinociceptive effect of morphine in a fish, rainbow trout.
There have been suggestions that analgesics be used by fish researchers. But in the absence of dose-response data for morphine, this suggestion seems imprudent. The purpose of the present study was to develop a dose-response relationship in fish using six doses of morphine. The response (movement of the fins or tail) to a noxious stimulus (electrical shock to the face region) was monitored before and after a dose of morphine intraperitoneally (i.p.). The i.p. dose of morphine ED(50) in rainbow trout was 6.7 ± 0.8 mg/kg (n = 12 at each dose). The plasma morphine concentration EC(50) was 4.1 ± 1.5 mg/L. In a second experiment, rainbow trout tested with equal amounts of morphine and naloxone (30 mg/kg) showed that the antinociceptive effect of morphine was blocked by naloxone. It has been suggested that stress-induced analgesia has been a confounding factor in some fish studies. However, plasma cortisol levels in our study indicated that stress was not a confounding factor in the present experiments. The ED(50) for morphine in fish was higher than that reported for humans or other mammals. Our observation showing a dose-response relation for morphine using a noxious stimulus supports arguments for its effectiveness as an antinociceptive drug in fish.


Computational Studies of Lipid Droplets.
Lipid droplets (LDs) are intracellular organelles whose primary function is energy storage. Known to emerge from the endoplasmic reticulum (ER) bilayer, LDs have a unique structure with a core consisting of neutral lipids, triacylglycerol (TG) or sterol esters (SE), surrounded by a phospholipid (PL) monolayer and decorated by proteins that come and go throughout their complex lifecycle. In this Feature Article, we review recent developments in computational studies of LDs, a rapidly growing area of research. We highlight how molecular dynamics (MD) simulations have provided valuable molecular-level insight into LD targeting and LD biogenesis. Additionally, we review the physical properties of TG from different force fields compared with experimental data. Possible future directions and challenges are discussed.


[Reflexion of French experts on the key points of the symposium].
The French experts present at the Eutherapy Symposium held in Prague confirmed the importance of left ventricular hypertrophy (LVH) and microalbuminuria as major independent risk factors for cardiovascular disease. Factors that must be considered for the treatment of hypertension in patients, particularly with type 2 diabetes. Professor J.M. Mallion stressed the contribution of thiazide and thiazide-like diruetics as indapamid, especially the 1.5 mg SR formulation. Professor F. Forette and Doctor O. Hanon recalled that the HYVET study is expected to confirm the beneficial effect of this same treatment on morbidity and mortality in very elderly patients. Professor O. Dubourg recalled the beneficial effect of indapamid SR on LVH demonstrated in the LIVE study. Likewise, Professor M. Marre emphasized its important impact on microalbuminuria as shown in the NESTOR study.


The von Willebrand factor-reducing activity of thrombospondin-1 is located in the calcium-binding/C-terminal sequence and requires a free thiol at position 974.
Plasma von Willebrand factor (VWF) is a multimeric protein that mediates adhesion of platelets to sites of vascular injury; however, only the very large VWF multimers are effective in promoting platelet adhesion in flowing blood. The multimeric size of VWF can be controlled by the glycoprotein, thrombospondin-1 (TSP-1), which facilitates reduction of the disulfide bonds that hold VWF multimers together. The TSP family of extracellular glycoproteins consists of 5 members in vertebrates, TSP-1 through TSP-4 and TSP-5/COMP. TSP-1 and TSP-2 are structurally similar trimeric proteins composed of disulfide-linked 150-kDa monomers. Recombinant pieces of TSP-1 and TSP-2 incorporating combinations of domains that span the entire subunit were produced in insect cells and examined for VWF reductase activity. VWF reductase activity was present in the Ca(++)-binding repeats and C-terminal sequence of TSP-1, but not of TSP-2. Alkylation of Cys974 in the C-terminal TSP-1 construct, which is a serine in TSP-2, ablated VWF reductase activity. These results imply that the reductase function of TSP-1 centers around Cys974 in the C-terminal sequence.


Neuropsychological sequelae of adolescent infectious diseases.
This article discusses the neuropsychological sequelae of adolescent infectious diseases. Primary care physicians are encouraged to extend their clinical activities beyond the primary medical care aspects of the infectious disease process to encompass a comprehensive, multidisciplinary, continuum of health care approach. Patient, disease, and socioecologic parameters are the foundation of this approach. This article is designed to help primary care physicians appreciate the complexity of neuropsychological infectious disease issues in the adolescent. Human immunodeficiency virus 1 (HIV-1) is emphasized because the legion of related sequelae demands a comprehensive health care approach and serves as a model for discussing other principal infectious diseases such as encephalitis (particularly Lyme disease) and bacterial meningitis.


Tissue electrical property mapping from zero echo-time magnetic resonance imaging.
The capability of magnetic resonance imaging (MRI) to produce spatially resolved estimation of tissue electrical properties (EPs) in vivo has been a subject of much recent interest. In this work we introduce a method to map tissue EPs from low-flip-angle, zero-echo-time (ZTE) imaging. It is based on a new theoretical formalism that allows calculation of EPs from the product of transmit and receive radio-frequency (RF) field maps. Compared to conventional methods requiring separation of the transmit RF field (B(1)(+)) from acquired MR images, the proposed method has such advantages as: 1) reduced theoretical error, 2) higher acquisition speed, and 3) flexibility in choice of different transmit and receive RF coils. The method is demonstrated in electrical conductivity and relative permittivity mapping in a salt water phantom, as well as in vivo measurement of brain conductivity in healthy volunteers. The phantom results show the validity and scan-time efficiency of the proposed method applied to a piece-wise homogeneous object. Quality of in vivo EP results was limited by reconstruction errors near tissue boundaries, which highlights need for image segmentation in EP mapping in a heterogeneous medium. Our results show the feasibility of rapid EP mapping from MRI without B(1)(+) mapping.


Thyroid hormone receptor binds to a site in the rat growth hormone promoter required for induction by thyroid hormone.
Transcription of the rat growth hormone (rGH) gene in pituitary cells is increased by addition of thyroid hormone (T3). This induction is dependent on the presence of specific sequences just upstream of the rGH promoter. We have partially purified T3 receptor from rat liver and examined its interaction with these rGH sequences. We show here that T3 receptor binds specifically to a site just upstream of the basal rGH promoter. This binding site includes two copies of a 7-base-pair direct repeat, the centers of which are separated by 10 base pairs. Deletions that specifically remove the T3 receptor binding site drastically reduce response to T3 in transient transfection experiments. These results demonstrate that T3 receptor can recognize specific DNA sequences and suggest that it can act directly as a positive transcriptional regulatory factor.


Isolation via next-generation sequencing of microsatellites from the Tasmanian macroalgae Lessonia corrugata (Lessoniaceae).
Microsatellite markers for the macroalgae Lessonia corrugata (Lessoniaceae) were developed, for the first time, to enable population genetic assessment of this important foundation species. Ion Torrent sequencing identified 16,622 loci, 29 of which were trialed in L. corrugata. Seven loci were found to be polymorphic and screened for variation in 76 individuals from two populations in Tasmania, Australia. Observed heterozygosity ranged from 0.086 to 0.686 (mean 0.386) and the number of alleles per locus ranged from two to five (mean 2.57). Heterozygosity was not significantly different from expected values. These loci can be used to study the population genetics of L. corrugata, a key habitat-forming species in the Tasmanian marine ecosystem, and will help to assess gene flow among spatially discrete populations such as those in marine protected areas.


Continuous systolic and diastolic blood pressure estimation utilizing long short-term memory network.
A novel blood pressure estimation method based on long short-term memory neural network, one of the recurrent neural networks being commonly used nowadays, is proposed in this paper for better chronic diseases monitoring. Along with the neural network, a newly proposed ambulatory blood pressure (ABP) processing technique called Two-stage Zero-order Holding (TZH) algorithm has also been presented in the paper. The proposed methodology has the advantages over traditional blood pressure estimation algorithms which are based on Pulse Transit time (PTT). The paper addresses the effectiveness of the algorithm by computing the Root-Mean-Squared Errors (RMSE) between the BP estimated and the ground truth. Our algorithm shows precise systolic blood pressure and diastolic blood pressure estimation with the average RMSE values in 2.751 mmHg and 1.604 mmHg respectively across the sample used. Experimental results suggest that BP estimation based on LSTM has great potential to be embedded into monitoring system for better accuracy and generalization.


Spi-1 and mutant p53 regulate different aspects of the proliferation and differentiation control of primary erythroid progenitors.
The emergence of leukemic cells in Friend virus complex-induced erythroleukemia is associated with two recurrent genetic alterations, namely the inactivation of the p53 tumor suppressor gene and the overexpression of Spi-1, a member of the Ets family of transcriptional regulators. In order to determine the role of these genetic alterations on the proliferation and differentiation control of erythroblasts, we expressed Spi-1 and the temperature sensitive mutant p53(V135A) in avian primary erythroid progenitors. We show that enforced expression of Spi-1 in erythroblasts obtained from bone marrow cells by expression of the ts-Sea tyrosine kinase inhibits the execution of the differentiation program normally induced in these cells in response to Epo and insulin and following inactivation of ts-Sea function. In contrast, overexpression of p53(V135A) is without effect on the ability of these cells to differentiate into erythrocytes. However, expression of p53(V135A) in erythroid progenitors obtained from bone marrow cells in the presence of SCF, TGF alpha and estradiol, was found to relieve these cells from their absolute TGF alpha requirement for long term proliferation. This phenotype is dependent upon the expression of the mutant form of p53(V135A) as it is not observed at a temperature at which p53(V135A) regains wild type p53 function. Our results show that each of the genetic alterations which characterize Friend erythroleukemic cells affect in a distinct manner the proliferation and differentiation control of primary erythroid progenitors.


Therapist fidelity with an exposure-based treatment of PTSD in adults with schizophrenia or schizoaffective disorder.
This study examined therapists' fidelity to a manualized, multicomponent cognitive-behavioral intervention for posttraumatic stress disorder (PTSD), including exposure therapy, among public sector patients with a psychotic disorder. Independent raters assessed therapists' competence and adherence, rating 20% of randomly selected audio taped sessions (n=57 sessions, coded by two raters, with strong interrater agreement). Adherence ratings indicated that therapists complied well with the protocol, and competency ratings typically averaged "very good" or higher (6 on 7-point Likert scale). Findings suggest that therapists can effectively deliver a manualized cognitive-behavioral intervention for PTSD, with exposure therapy, to patients with severe mental illness without compromise to the structure of sessions and/or the therapeutic relationship.


Identification of two mammalian reductases involved in the two-carbon fatty acyl elongation cascade.
The de novo synthesis of fatty acids occurs in two distinct cellular compartments. Palmitate (16:0) is synthesized from acetyl-CoA and malonyl-CoA in the cytoplasm by the enzymes acetyl-CoA carboxylase 1 and fatty acid synthase. The synthesis of fatty acids longer than 16 carbons takes place in microsomes and utilizes malonyl-CoA as the carbon source. Each two-carbon addition requires four sequential reactions: condensation, reduction, dehydration, and a final reduction to form the elongated fatty acyl-CoA. The initial condensation reaction is the regulated and rate-controlling step in microsomal fatty acyl elongation. We previously reported the cDNA cloning and characterization of a murine long chain fatty acyl elongase (LCE) . Overexpression of LCE in cells resulted in the enhanced addition of two-carbon units to C12-C16 fatty acids, and evidence was provided that LCE catalyzed the initial condensation reaction of long chain fatty acid elongation. The remaining three enzymes in the elongation reaction have not been identified in mammals. Here, we report the identification and characterization of two mammalian enzymes that catalyze the 3-ketoacyl-CoA and trans-2,3-enoyl-CoA reduction reactions in long and very long chain fatty acid elongation, respectively.


Tolerability of a rapid-escalation vinblastine-prednisolone protocol in dogs with mast cell tumours.
Optimal chemotherapy protocols for high-risk mast cell tumours (MCTs) are unknown. The purpose of this study was to determine the tolerability and toxicity profile of a rapidly escalating vinblastine and prednisolone protocol (VPP) in which 3.00 mg/m2 was administered once 7 days apart: at day 14 and at day 21. Dogs with chemotherapy-naïve MCTs presenting to the Oncology Service of a single institution were prospectively enrolled to receive escalating vinblastine, and haematology and a standardised quality-of-life questionnaire were assessed prior to each dosage. Thirty-four dogs were included: 30 with microscopic disease treated with adequate local therapy and four with macroscopic disease. Of 220 doses of vinblastine administered, 4% were associated with grade 3 and 4 toxicity. A total of 70% of dogs tolerated 3.00 mg/m2 given 7 days apart at day 14 and 21, although 29% of dogs developed dose-limiting toxicities and 8% discontinued the protocol due to toxicity. In conclusion, VPP was well-tolerated overall, although prior to further dose intensity optimisation, it is important to determine if dose intensity is linked to outcome in canine MCT to avoid unwarranted toxicity.


Nerve injuries after dental injection: a review of the literature.
Prolonged and possibly permanent change in sensation due to nerve damage can occur after dental injections. Although the condition is rare, many practitioners will see this form of nerve injury during their careers. The exact mechanism of the injury has yet to be determined, and little can be done to prevent its occurrence. This type of injury carries with it many functional and psychological implications, and referral to both dental and medical specialists may be necessary for continued follow-up and possible treatment.