A salient and task-irrelevant collinear structure hurts visual search.
Salient distractors draw our attention spontaneously, even when we intentionally want to ignore them. When this occurs, the real targets close to or overlapping with the distractors benefit from attention capture and thus are detected and discriminated more quickly. However, a puzzling opposite effect was observed in a search display with a column of vertical collinear bars presented as a task-irrelevant distractor [6]. In this case, it was harder to discriminate the targets overlapping with the salient distractor. Here we examined whether this effect originated from factors known to modulate attentional capture: (a) low probability-the probability occurrence of target location at the collinear column was much less (14%) than the rest of the display (86%), and observers might strategically direct their attention away from the collinear distractor; (b) attentional control setting-the distractor and target task interfered with each other because they shared the same continuity set in attentional task; and/or (c) lack of time to establish the optional strategy. We tested these hypotheses by (a) increasing to 60% the trials in which targets overlapped with the same collinear distractor columns, (b) replacing the target task to be connectivity-irrelevant (i.e., luminance discrimination), and (c) having our observers practice the same search task for 10 days. Our results speak against all these hypotheses and lead us to conclude that a collinear distractor impairs search at a level that is unaffected by probabilistic information, attentional setting, and learning.


Metabolism-mediated drug interactions associated with ritonavir-boosted tipranavir in mice.
Tipranavir (TPV) is the first nonpeptidic protease inhibitor used for the treatment of drug-resistant HIV infection. Clinically, TPV is coadministered with ritonavir (RTV) to boost blood concentrations and increase therapeutic efficacy. The mechanism of metabolism-mediated drug interactions associated with RTV-boosted TPV is not fully understood. In the current study, TPV metabolism was investigated in mice using a metabolomic approach. TPV and its metabolites were found in the feces of mice but not in the urine. Principal component analysis of the feces metabolome uncovered eight TPV metabolites, including three monohydroxylated, three desaturated, one dealkylated, and one dihydroxylated. In vitro study using human liver microsomes recapitulated five TPV metabolites, all of which were suppressed by RTV. CYP3A4 was identified as the primary enzyme contributing to the formation of four TPV metabolites (metabolites II, IV, V, and VI), including an unusual dealkylated product arising from carbon-carbon bond cleavage. Multiple cytochromes P450 (2C19, 2D6, and 3A4) contributed to the formation of a monohydroxylated metabolite (metabolite III). In vivo, RTV cotreatment significantly inhibited eight TPV metabolic pathways. In summary, metabolomic analysis revealed two known and six novel TPV metabolites in mice, all of which were suppressed by RTV. The current study provides solid evidence that the RTV-mediated boosting of TPV is due to the modulation of P450-dependent metabolism.


Selective anticancer effects of 3',5'-dioctanoyl-5-fluoro-2'-deoxyuridine, a lipophilic prodrug of 5-fluoro-2'-deoxyuridine, dissolved in an oily lymphographic agent on hepatic cancer of rabbits bearing VX-2 tumor.
3',5'-Dioctanoyl-5-fluoro-2'-deoxyuridine (FdUrd-C8), one of the lipophilic prodrugs of 5-fluoro-2'-deoxyuridine (FdUrd) was dissolved in an oily lymphographic agent (Lipiodol Ultra-Fluid), which had been studied as a carrier of the anticancer drug for hepatic cancer. The prodrug was administered into the left proper hepatic artery of rabbits bearing VX-2 tumor in the liver in order to examine the anticancer effects and possible adverse effects on nontumorous hepatic cells. Lipiodol or FdUrd-C8*Lipiodol selectively remained in the hepatic cancer area but disappeared from nontumorous parts of the liver 7 days after injection. Tumor growth rates in 1 week of the untreated group, a group given injections of 0.2 ml of Lipiodol alone, and groups given injections of 0.2 ml of Lipiodol containing 30, 50, 70, and 100 mg of FdUrd-C8 were 636, 436, 34.8, 14.9, -2.4, and -10.4% of the size at the time of treatment, respectively. Pathological observation also showed that FdUrd-C8 had a strong anticancer effect on VX-2 tumor growing in the liver of the rabbits. In contrast to the effect on the cancerous cells, that on nontumorous hepatic cells was very slight. In pathological observation, necrosis or degeneration of nontumorous hepatic cells was hardly observed. Plasma glutamic-oxaloacetic transaminase and glutamic-pyruvic transaminase levels temporarily rose 1 day after injection but returned to the initial levels within 7 days in all groups.


The Short-Term Effect of Dynamic Tape versus the Low-Dye Taping Technique in Plantar Fasciitis: A Randomized Clinical Trial.
Plantar fasciitis is a painful disorder that affects the plantar fascia of the foot, with a multifactorial aetiology. Dorsal flexion deficiency in the ankle is a risk factor for it. The provisional use of taping is described as part of conservative treatment. Dynamic Tape® is a type of tape that, adhered to muscles, allows for potential elastic energy to accumulate and dissipate later, optimizing its function. Therefore, it can offer immediate benefits while the patient awaits definitive treatment depending on the cause. To verify the effectiveness of Dynamic Tape® and the low-dye taping technique on pain intensity, ankle range of motion, and foot posture index. A randomised, double-blind clinical trial was conducted. A total of 57 subjects from the Clinical Podiatry Area of the University of Seville (Spain), clinically diagnosed with plantar fasciitis, were randomized into two groups. For one week, in the gastrocnemius-Achilles-plantar system, one group was treated with Dynamic Tape® and another group with low-dye taping. Pain, degrees of movement of dorsal flexion, and the foot posture index were measured in both groups before the intervention and one week after the intervention. A repeated-measures analysis of variance (ANOVA) was used to explore the differences between groups. Significant differences in the decrease in pain intensity using Dynamic Tape® were found when comparing the treatments (p = 0.015) and the foot posture index was more normal in low-dye taping (p < 0.001). In both cases, the treatment showed similar behaviour with respect to the dorsal flexion ankle movement. The effectiveness of Dynamic Tape®, compared to that of the low-dye taping, has a major benefit with regard to pain intensity from fasciitis, although it does not produce changes in the ankle range of motion and foot posture index. Consequently, Dynamic Tape® can be considered a taping technique with beneficial effects on pain intensity in the provisional approach to plantar fasciitis.


Sediminibacterium roseum sp. nov., isolated from sewage sediment.
A novel bacterial strain, designated SYL130T, was isolated from the sewage sediment of a park in Busan, Korea. The strain was aerobic, producing orange colonies on R2A agar. Cells were single, Gram-stain-negative rods and were motile by gliding. Phylogenetic analyses, based on 16S rRNA gene sequences, showed that strain SYL130T was most closely related to Sediminibacterium aquarii JCM 31013T (96.1 %). The major fatty acids (>5 % of the total) of strain SYL130T were iso-C15 : 0 (28.3 %), iso-C15 : 1 G (23.2 %), iso-C17 : 0 3-OH (9.6 %), anteiso-C15 : 0 (5.9 %) and iso-C16 : 0 3-OH (5.6 %). The major polar lipids were phosphatidylethanolamine, one unidentified phospholipid, one unidentified aminolipid, two unidentified aminophospholipids and six unidentified polar lipids. The predominant respiratory quinone was MK-7. The DNA G+C content was 47.8 mol%. Strain SYL130T had clearly differential characteristics to related species including the temperature and pH ranges for growth, and being positive for l-arabinose and maltose, and negative for α-galactosidase activity. On the basis of phenotypic, chemotaxonomic and genotypic analyses, strain SYL130T represents a novel species of the genus Sediminibacterium, for which the name Sediminibacterium roseum sp. nov., is proposed. The type strain Sediminibacterium roseum is SYL130T (=KCTC 52860T=CCTCC AB 2017082T).


Biology of heterotrimeric G-protein signaling.
The G proteins are components of a complex membrane signaling system designed to modulate extracellular signals as they are transmitted into the cell. The principal components are the receptor, the G proteins including the alpha, beta, gamma subunits and the effector. Associated with these molecules are several molecular processes by which the signal is transmitted, and regulated including desensitization. Molecules such as arrestin, the RGS (regulators of the G-protein signaling) as well as downstream kinases associated with cyclic AMP are key to regulating the G protein signal. Membrane lipids are key for both anchoring this signal system to the plasma membrane but also in defining the signaling process. Through understanding the biology of the signal system, a number of diseases have been linked to dysfunction of the G protein system. It is clear that this important membrane signal system will become the target for more intense investigation and pharmacologic manipulation to treat critical illness.


[Tenoxicam (texamen) in the treatment of acute cervicalgia: results of an open comparative trial].
Acute cervical pain is one of the most common reasons for a visit to a doctor and temporal disability. We studied efficacy and safety of the nonsteroid anti-inflammatory drug tenoxicam (texamen) in the treatment of acute cervical pain in myofascial syndrome. A trial included 50 people (42 women and 8 men, mean age 42,2±6,8 years) with acute cephalgia. A main group (30 patients) received tenoxicam in dose 20 mg daily in the morning during 7 days with simultaneous therapeutic exercises with elements of postisometric relaxation of cervical muscles. A control group (20 patients) received myorelaxants and massage of a cervical-collar zone. The analgesic effect was more rapid in patients treated with texamen compared to controls. Statistically significant differences were seen in 1-3 days of treatment. In the main group, the analgesic effect long, only 16,6% of patients reported the aggravation of pain in the evening hours during the first day of treatment and 10% in the 2nd day; 23,3% patients of the main group used an additional dose of texamen, another nonsteroid anti-inflammatory drug (ibuprofen) or triptan to stop pain. The introduction of nonsteroid anti-inflammatory drugs, in particular texamen, in the complex treatment of acute cephalgia can significantly reduce pain syndrome.


A modified plate holding system for anaerobic cultures.
A modified plate holding system for anaerobes has been developed which: 1) effectively reduces the volume of oxygen-free gas required, 2) promotes earlier bacterial growth, and 3) monitors the anaerobic atmosphere of the holding vessel and the rate of gas flow. Cultures of Bacteroides fragilis, Clostridium perfringens, C. septicum, Fusobacterium nucleatum, Peptococcus sp. and Propionibacterium sp. were evaluated for optimal growth. All cultures grew as well as or better when preincubated in the holding system for one to three hours then incubated in a GasPak system for the remainder of the 24 hours, as compared to incubation only in the GasPak or holding system for the entire 24-hour period.


Accessibility of promoter DNA is not the primary determinant of chromatin-mediated gene regulation.
DNA accessibility is thought to be of major importance in regulating gene expression. We test this hypothesis using a restriction enzyme as a probe of chromatin structure and as a proxy for transcription factors. We measured the digestion rate and the fraction of accessible DNA at almost all genomic AluI sites in budding yeast and mouse liver nuclei. Hepatocyte DNA is more accessible than yeast DNA, consistent with longer linkers between nucleosomes, suggesting that nucleosome spacing is a major determinant of accessibility. DNA accessibility varies from cell to cell, such that essentially no sites are accessible or inaccessible in every cell. AluI sites in inactive mouse promoters are accessible in some cells, implying that transcription factors could bind without activating the gene. Euchromatin and heterochromatin have very similar accessibilities, suggesting that transcription factors can penetrate heterochromatin. Thus, DNA accessibility is not likely to be the primary determinant of gene regulation.


Alpha-heavy chain disease. Report of a case with spontaneous regression.
The occurrence of alpha-heavy chain disease in an Italian adult, working in Libya, is reported, characterized by a spontaneous clinical and immunological recovery. It is suggested that the patient could have acquired the disease during his stay in an endemic area of alpha-heavy chain disease, and that the observed spontaneous remission could be related to the removal of environmental pathogenic factors, following his departure from Libya.


Long Non-Coding RNA SNHG7 Alleviates Oxygen and Glucose Deprivation/Reoxygenation-Induced Neuronal Injury by Modulating miR-9/SIRT1 Axis in PC12 Cells: Potential Role in Ischemic Stroke.
The roles of long non-coding RNA (lncRNAs) in ischemic stroke (IS) have been widely illustrated. Here, we focused on the function and mechanism of lncRNA SNHG7 in IS. Middle cerebral artery occlusion (MCAO) was used for inducing mice to establish IS models in vivo. Oxygen and glucose deprivation/reoxygenation (OGD/R) was used for treating PC12 cells to establish IS models in vitro. Relative expression of SNHG7 and miR-9 was determined by qRT-PCR. The neuronal injury was assessed by measuring relative activity of ROS, malondialdehyde (MDA) level and cell viability. Cell viability was determined by MTT assay. Dual-luciferase reporter (DLR) assay was employed to test the target of SNHG7 or miR-9. Western blot was used to determine the protein expression of SIRT1. Apoptosis rate was measured by flow cytometry. SNHG7 was down-regulated and miR-9 was up-regulated by MCAO treatment in brain tissues of mice and by OGD/R treatment in PC12 cells. Overexpression of SNHG7 or suppression of miR-9 decreased the relative activity of ROS and the MDA level as well as enhancing cell viability, and SNHG7 reduced apoptosis rate in OGD/R-induced PC12 cells (IS cells). MiR-9 was targeted by SNHG7 and SIRT1 was targeted by miR-9. The protein expression of SIRT1 was reduced by OGD/R treatment in PC12 cells. The suppressive effects of SNHG7 on the relative activity of ROS, the MDA level and apoptosis rate as well as the promotion effect of SNHG7 on cell viability were reversed by miR-9 mimics or sh-SIRT1 in IS cells. LncRNA SNHG7 alleviated OGD/R-induced neuronal injury by mediating miR-9/SIRT1 axis in vitro.


MiR-144 regulates hematopoiesis and vascular development by targeting meis1 during zebrafish development.
Hematopoiesis is a dynamic process by which peripheral blood lineages are developed. It is a process tightly regulated by many intrinsic and extrinsic factors, including transcriptional factors and signaling molecules. However, the epigenetic regulation of hematopoiesis, for example, regulation via microRNAs (miRNAs), remains incompletely understood. Here we show that miR-144 regulates hematopoiesis and vascular development in zebrafish. Overexpression of miR-144 inhibited primitive hematopoiesis as demonstrated by a reduced number of circulating blood cells, reduced o-dianisidine staining of hemoglobin, and reduced expression of hbαe1, hbβe1, gata1 and pu.1. Overexpression of miR-144 also inhibited definitive hematopoiesis as shown by reduced expression of runx1 and c-myb. Mechanistically, miR-144 regulates hematopoiesis by repressing expression of meis1 involved in hematopoiesis. Both real-time RT-PCR and Western blot analyses showed that overexpression of miR-144 repressed expression of meis1. Bioinformatic analysis predicts a target binding sequence for miR-144 at the 3'-UTR of meis1. Deletion of the miR-144 target sequence eliminated the repression of meis1 expression mediated by miR-144. The miR-144-mediated abnormal phenotypes were partially rescued by co-injection of meis1 mRNA and could be almost completely rescued by injection of both meis1 and gata1 mRNA. Finally, because meis1 is involved in vascular development, we tested the effect of miR-144 on vascular development. Overexpression of miR-144 resulted in abnormal vascular development of intersegmental vessels in transgenic zebrafish with Flk1p-EGFP, and the defect was rescued by co-injection of meis1 mRNA. These findings establish miR-144 as a novel miRNA that regulates hematopoiesis and vascular development by repressing expression of meis1.


Risk factors of developing the hungry bone syndrome after parathyroidectomy for primary hyperparathyroidism.
Around 13% of patients undergoing parathyroidectomy for primary hyperparathyroidism (PHPT) postoperatively develop a condition known as the hungry bone syndrome (HBS). Although the condition is quite prevalent, the research in this field is very limited. The aim of our study was to determine possible risk factors of developing HBS after parathyroidectomy for PHPT. In this study we enrolled patients who underwent parathyroidectomy for PHPT from January 2005 to December 2016 and performed a retrospective analysis. We used the definition of HBS as hypocalcaemia with normal or elevated PTH values. Patients were divided into two groups by the postoperative HBS prevalence: patients with postoperative HBS and those without postoperative HBS. In all, 94 patients were included into the final analysis. We found that patients who developed HBS more often underwent parathyroidectomies simultaneously with a thyroid surgery, underwent longer operations (73.9 ± 41.7 vs. 102.4 ± 44.8 minutes; p = 0.001), and had heavier parathyroid glands removed (0.6 (0.3-8.0) vs. 0.8 (0.15-14.0) g; p = 0.041). Also, these patients had higher preoperative PTH values (15.3 (6.1-63.7) vs. 22.4 (9.2-47.8) pmol/l; p = 0.003). From the ROC curve of the preoperative PTH values and the development of the hungry bone syndrome (AUC = 0.721 (95% CI 0.59-0.85); p = 0.003) we found a 45 pmol/l PTH cut-off value that shows a 90% tendency to develop postoperative HBS. Patients undergoing longer parathyroidectomies and those with heavier removed parathyroid glands tend to develop HBS. A preoperative PTH value higher than 45 pmol/l determines an over 90% risk of developing HBS.


Insulin induced fetal hypoglycaemia and fetal and maternal plasma prostaglandin concentrations in sheep in late gestation.
Fetal hypoglycaemia consequent on food withdrawal for 48 h in sheep in late pregnancy is accompanied by an increase in fetal PGE2 plasma concentrations and myometrial contractility. To assess the contribution of fetal hypoglycaemia and related cellular glucopenia in the increased production of fetal PGE2 we studied the effect of 48 h insulin infusion to the fetus. Fetal whole blood glucose was lowered from 19 +/- 2 to 9 +/- 1 mg.dl-1. This experimental regimen maintains glucose availability to those fetal cells in which insulin increases glucose uptake. Fetal umbilical venous and femoral arterial PGE2 concentrations and umbilical veno-arterial PGE2 difference were unchanged, but maternal uterine veno-arterial difference for PGFM increased during the insulin induced fetal hypoglycaemia. Myometrial activity was also unchanged. We conclude that the increased fetal PGE concentration previously reported during food withdrawal is due to a deficiency of glucose to specific insulin dependent cells within vascular beds served by the fetal cardiovascular system. In addition, the findings suggest a need for a supply of glucose of fetal origin for cells that are responsible for increased PGFM concentrations in the maternal uteroplacental circulation.


Effect of miR-146a polymorphism on lipoic acid therapy in patients with T2DM peripheral polyneuropthy.
For investigating the impact of miR-146a rs2910164 polymorphism on the therapeutic efficacy of lipoic acid therapy in patients with type 2 diabetes mellitus (T2DM) peripheral neuropathy (DPN). 106 T2DM-DPN patients in our hospital from Jan. 2020- 2022 were selected. The probe detection method was utilized to determine the polymorphism of the miR-146a rs2910164 gene in peripheral blood. All patients were treated with zinc sulfate for 3 weeks period. According to the treatment effect, 37 patients who were ineffective in treatment will be divided into an ineffective group, and 79 patients who were effective in treatment will be divided into an effective group. The condition of miR-146a gene peptides was analyzed after treatment in both groups. The motor nerve conduction velocity (MNCV), sensory nerve conduction velocity (SNCV), and Toronto Clinical Scoring System (TCSS) scores of the median nerve and common peroneal nerve with different genotypes were compared between the 2 sets. The genotype frequencies of alleles G, GG, and GC in the valid group were lower than those in the invalid group; After treatment, MNCV and SNCV of CC genotype median nerve and common peroneal nerve in DPN patients were higher than those before treatment; The TCSS scores of the three genotypes less than post-treatment. The above results showed statistically significant differences (P<0.05). Lipoic acid is influenced by the miR-146a polymorphism gene in the treatment of T2DM-DPN patients, with the CC genotype having a lower susceptibility and the best clinical treatment effect.


Development of a defined medium and two-step culturing method for improved exotoxin A yields from Pseudomonas aeruginosa.
A two-step method is described for the production of exotoxin A by Pseudomonas aeruginosa in which a defined growth medium is modified for the toxin production phase. As a result, specific exotoxin A yields comparable to those obtained with complex media were achieved. In the development of this two-step process, several divalent metallic cations (Ca2+, Cu2+, and Mn2+), in addition to iron, were found to inhibit the yield of exotoxin A while Ca2+ and glycerol were found to increase yields. Northern blot analysis of total RNA isolates suggests that these effects on exotoxin A yields are based on events at the transcription level.


Initial employment status of resident physicians completing training in 1995.
To assess the degree and type of difficulty encountered by resident physicians attempting to enter the workforce in 1995. Employment information derived from a 1-page descriptive survey completed by residency program directors from January 1, 1996, to June 15,1996, is described and compared with the results of a similar survey completed 1 year earlier. Directors of 4568 residency programs in 31 specialties and subspecialties accredited by the Accreditation Council for Graduate Medical Education. The number of 1995 program graduates, their current professional status, and program directors' characterization of the experience of graduates who entered clinical practice, including the number who experienced major difficulties securing an acceptable practice position. Program directors reported actual and anticipated decreases in the number of residency positions and the likely availability of future professional opportunities. The 3819 program directors (83.6%) who completed the survey reported that 20065 resident physicians completed a residency program during 1995. Of those seeking employment (n = 13215), most entered clinical practice (80.1%) or took an academic position (15.6%); 2.2% were unemployed or had taken a position in a specialty or subspecialty different from the one in which they were last trained. A portion (6.3%) of graduates who entered clinical practice in their specialty or subspecialty experienced difficulty finding a suitable position; the percentage was lowest among graduates of general surgery, psychiatry, and primary care specialties. Survey results regarding the 1995 graduates are consistent with those obtained regarding the 1994 graduates and suggest that the market for physician services in some disciplines continues to be restrictive. We found that graduates of the specialties of anesthesiology and plastic surgery, whom we reported had the greatest difficulty finding acceptable positions in 1994, had less difficulty in 1995, suggesting a possible improvement in the market, less competition, a change in the respondents' perception of "acceptable," or a change in the resident physicians' willingness to pursue different opportunities. The general consistency of our results and their congruence with other published data suggest that this method is useful to identify and monitor trends in the physician market.


Proof of dual-topology architecture of Fluc F- channels with monobody blockers.
Fluc-type F(-) channels--used by microorganisms for resisting fluoride toxicity--are unusual in their quaternary architecture: they are thought to associate as dimers with the two subunits in antiparallel transmembrane orientation. Here, we subject this unusual structural feature to a direct test. Single purified Fluc channels recorded in planar lipid bilayers are constitutively open, with rare, short-lived closings. Using combinatorial libraries, we generated synthetic binding proteins, 'monobodies,' that specifically bind to Fluc homologues with nanomolar affinity. Reversible binding of monobodies to two different Fluc channel homologues is seen in single-channel recordings as long-lived nonconducting events that follow bimolecular kinetics. By applying monobodies sequentially to the two sides of the bilayer in a double-sided perfusion manoeuvre, we show that Fluc channels present monobody-binding epitopes to both sides of the membrane. The result establishes that Fluc subunits are arranged in dimeric antiparallel orientation.


Galactosamine induced hepatitis induces a reduction in hepatocyte epidermal growth factor receptors.
The rapid regenerative response of the rat liver to partial hepatectomy is associated with a decline in liver epidermal growth factor receptor numbers which implies that ligand epidermal growth factor receptor interactions maybe important in initiating and/or modulating this process. The proliferative process in toxic hepatitis (where in contrast with partial hepatectomy the majority of hepatocytes have been exposed to damaging influences) has been less widely investigated. We studied the DNA synthetic response of rat livers to toxic injury induced by a 350 or 800 mg/kg ip injection of galactosamine and that caused by 70% hepatectomy, comparing the changes in epidermal growth factor receptor status. Both resulted in down regulation of epidermal growth factor receptors, suggesting similar ligand epidermal growth factor receptor binding occurs during the proliferative response after galactosamine administration and after partial hepatectomy. In vitro studies on isolated hepatocytes showed that epidermal growth factor receptor down regulation was not a direct effect of galactosamine on hepatocyte membranes.


Vulnerability of ecosystems to climate change moderated by habitat intactness.
The combined effects of climate change and habitat loss represent a major threat to species and ecosystems around the world. Here, we analyse the vulnerability of ecosystems to climate change based on current levels of habitat intactness and vulnerability to biome shifts, using multiple measures of habitat intactness at two spatial scales. We show that the global extent of refugia depends highly on the definition of habitat intactness and spatial scale of the analysis of intactness. Globally, 28% of terrestrial vegetated area can be considered refugia if all natural vegetated land cover is considered. This, however, drops to 17% if only areas that are at least 50% wilderness at a scale of 48×48 km are considered and to 10% if only areas that are at least 50% wilderness at a scale of 4.8×4.8 km are considered. Our results suggest that, in regions where relatively large, intact wilderness areas remain (e.g. Africa, Australia, boreal regions, South America), conservation of the remaining large-scale refugia is the priority. In human-dominated landscapes, (e.g. most of Europe, much of North America and Southeast Asia), focusing on finer scale refugia is a priority because large-scale wilderness refugia simply no longer exist. Action to conserve such refugia is particularly urgent since only 1 to 2% of global terrestrial vegetated area is classified as refugia and at least 50% covered by the global protected area network.


Interfacility Transfer Directly to the Neuroangiography Suite in Acute Ischemic Stroke Patients Undergoing Thrombectomy.
In patients identified at referring facilities with acute ischemic stroke caused by a large vessel occlusion, bypassing the emergency department (ED) with direct transport to the neuroangiography suite may safely shorten reperfusion times. We conducted a single-center retrospective review of consecutive patients transferred to our facility for consideration of endovascular therapy. Patients were identified as admitted directly to the neuroangiography suite (DAN), transferred to the ED before intra-arterial therapy (ED-IA), and transferred to the ED but did not receive IA therapy (ED-IV). A retrospective review of a prospectively maintained database of transfer patients between January 2013 and October 2016 with large vessel occlusions identified 108 ED-IV patients and 261 patients who underwent mechanical thrombectomy (DAN=111 patients and ED-IA=150 patients). There were no differences in baseline characteristics among the 3 groups. The median computed tomography ASPECTS (Alberta Stroke Program Early CT Score) was lower in the ED-IV group versus the ED-IA and DAN groups (8 versus 9; P=0.001). In the DAN versus ED-IA cohort, there were comparable rates of TICI2b/3 recanalization and access to recanalization time. There was significantly faster hospital arrival to groin access time in the DAN cohort (81 minutes versus 22 minutes; P=0.001). Functional independence at 90 days was comparable in the DAN versus ED-IA cohorts but worse in the ED-IV group (43% versus 44% versus 22%; P=0.001). DAN is safe, feasible, and associated with faster times of hospital arrival to recanalization. The clinical benefit of this approach should be assessed in a prospective randomized trial.


Cyberknife stereotactic radiosurgery and radiation therapy treatment planning system.
CyberKnife is an image-guided stereotactical dose delivery system designed for both focal irradiation and radiation therapy (SRT). Focal irradiation refers the use of many small beams to deliver highly focus dose to a small target region in a few fractions. The system consists of a 6-MV linac mounted to a robotic arm, coupled with a digital x-ray imaging system. The radiation dose is delivered using many beams oriented at a number of defined or nodal positions around the patients. The CyberKnife can be used for both intracranial and extracranial treaments unlike the Gamma Knife which is limited to intracranial cases. Multiplan (Accuray Inc., Sunnyvale, CA) is the treatment planning system developed to cooperate with this accurate and versatile SRS and SRT system, and exploit the full function of Cyberknife in high-precision radiosurgery and therapy. Optimized inverse treatment plan can be achieved by fine-tuning contours and planning parameters. Precision is the newest version of Cyberknife treatment planning system (TPS) and an upgrade to Multiplan. It offers several new features such as Monte Carlo for multileaf collimator (MLC) and retreatment for other modalities that added more support for the Cyberknife system. The Cybeknife TPS is an easy-to-use and versatile inverse planning platform, suitable for stereotactic radiosurgery and radiation therapy. The knowledge and experience of the planner in this TPS is essential to improve the quality of patient care.


A cryptic plasmid from Shigella sonnei.
pNZ500 is a 1.5 kb cryptic plasmid from a Shigella sonnei isolate. It was introduced into Escherichia coli by cotransformation, where it is maintained at about 30 copies per chromosome equivalent. Hybridization studies show that pNZ500 exhibits a high level of sequence similarity to other 1.5 kb plasmids found in different S. sonnei isolates but shares no homology with larger S. sonnei plasmids. pNZ500 shares a small degree of sequence homology with pBR322 and with pAC184. The homology with pBR322 is restricted to sequences close to the ori-bom region of this plasmid. Nevertheless, pNZ500 maintenance in E. coli is not dependent on DNA polymerase I activity, and does depend on continuing protein synthesis. pNZ500 encodes two polypeptide gene products whose monomer molecular weights are 24500 and 18000. The examination of host cells for the expression of possible plasmid phenotypes revealed no differences between cells bearing pNZ500 and plasmidless cells.


Longitudinal Antibody Responses in People Who Inject Drugs Infected With Similar Human Immunodeficiency Virus Strains.
Multiple factors influence the human immunodeficiency virus (HIV) antibody response produced during natural infection, leading to responses that can vary in specificity, strength, and breadth. People who inject drugs identified as recently infected with HIV (n = 23) were analyzed for clustering of their viral sequences (genetic distance, <2%). Longitudinal antibody responses were identified for neutralizing antibody (Nab) potential, and differences in antibody subclass, specificity, and Fc receptor ligation using pseudovirus entry and multiplexed Fc array assays, respectively. Responses were analyzed for differences between subject groups, defined by similarity in the sequence of the infecting virus. Viral sequences from infected individuals were grouped into 3 distinct clusters with 7 unclustered individuals. Subjects in cluster 1 generally had lower antibody response magnitudes, except for antibodies targeting the V1/V2 region. Subjects in clusters 2 and 3 typically had higher antibody response magnitudes, with the Fv specificity of cluster 2 favoring gp140 recognition. NAb responses differed significantly between clusters for 3 of 18 pseudoviruses examined (P < .05), but there were no differences in overall NAb breadth (P = .62). These data demonstrate that individuals infected with similar viral strains can generate partially similar antibody responses, but these do not drastically differ from those in individuals infected with relatively unrelated strains.


Ongoing and stimulus-evoked activity of sympathetically correlated neurons in the intermediate zone and dorsal horn of acutely spinalized rats.
We have shown previously that in the acutely spinalized anesthetized rat the activities of many dorsal horn interneurons (DHN) at the T(10) level are correlated positively with both ongoing and stimulus-evoked renal sympathetic nerve activity (RSNA) and therefore may belong to networks generating RSNA after acute, cervical, spinal transection. In the present study, we recorded from both DHN and interneurons in the intermediate zone (IZN) of the T(10) spinal segment in acutely C(1)-transected, chloralose-anesthetized, artificially respired rats. The activities of a similar percentage of IZN and DHN were correlated positively with ongoing RSNA, but the peaks of spike-triggered averages of RSNA based on the activity of IZN were larger, relative to dummy averages, than spike-triggered averages of RSNA based on the activity of DHN. Sympathetically correlated DHN and IZN differed in their responses to noxious somatic stimuli. Most correlated DHN had relatively simple somatic fields; they were excited by noxious stimulation of the T(10) and nearby dermatomes and inhibited by stimulation of more distal dermatomes. As we have shown previously, the excitatory and inhibitory fields of these neurons were very similar to fields that, respectively, excited and inhibited RSNA. On the other hand, the somatic fields of 50% of sympathetically correlated IZN were significantly more complex, indicating a difference between either the inputs or the processing properties of IZN and DHN. Sympathetically correlated IZN and DHN also differed in their responses to colorectal distension (CRD), a noxious visceral stimulus. CRD increased RSNA in 11/15 rats and increased the activity of most sympathetically correlated T(10) IZN. On the other hand, CRD decreased the activity of a majority of sympathetically correlated T(10) DHN. These observations suggest that the same stimulus may differentially affect separate, putative, sympathoexcitatory pathways, exciting one and inhibiting the other. Thus the magnitude and even the polarity of responses to a given stimulus may be determined by the modality and location of the stimulus, the degree to which multiple pathways are affected by the stimulus, and the ongoing activity of presympathetic neurons, at multiple rostrocaudal levels, before stimulation. A multipathway system may explain the variability in autonomic responses to visceral and somatic stimuli exhibited in spinally injured patients.


A novel promiscuous class of camelid single-domain antibody contributes to the antigen-binding repertoire.
It is well established that, in addition to conventional Abs, camelids (such as Camelus dromedarius and Lama glama) possess unique homodimeric H chain Abs (HCAbs) devoid of L chains. The Ag-binding site of these HCAbs consists of a single variable domain, referred to as VHH. It is widely accepted that these VHHs, with distinct framework-2 imprints evolved within the V(H) clan III-family 3, are exclusively present on HCAbs. In this study, we report the finding of a distinct leader signal sequence linked to variable genes displaying a high degree of homology to the clan II, human VH(4) family that contributes to the HCAb Ag-binding diversity. Although the VHH framework-2 imprints are clearly absent, their VH(4)-D-JH recombination products can be rearranged to the H chains of both classical and HCAbs. This suggests that for these V domains the presence of a L chain to constitute the Ag-binding site is entirely optional. As such, the capacity of this promiscuous VH(4) family to participate in two distinct Ab formats significantly contributes to the breadth of the camelid Ag-binding repertoire. This was illustrated by the isolation of stable, dendritic cell-specific VH(4) single domains from a VH(4)-HCAb phage display library. The high degree of homology with human VH(4) sequences is promising in that it may circumvent the need for "humanization" of such single-domain Abs in therapeutic applications.


Seasonal Influenza and Avian Influenza A(H5N1) Virus Surveillance among Inpatients and Outpatients, East Jakarta, Indonesia, 2011-2014.
During October 2011-September 2014, we screened respiratory specimens for seasonal and avian influenza A(H5N1) virus infections among outpatients with influenza-like illness and inpatients with severe acute respiratory infection (SARI) in East Jakarta, an Indonesia district with high incidence of H5N1 virus infection among poultry. In total, 31% (1,875/6,008) of influenza-like illness case-patients and 15% (571/3,811) of SARI case-patients tested positive for influenza virus. Influenza A(H1N1)pdm09, influenza A(H3N2), and influenza B virus infections were detected in all 3 years, and the epidemic season extended from November through May. Although 28% (2,810/10,135) of case-patients reported exposure to poultry, only 1 SARI case-patient with an H5N1 virus infection was detected. Therefore, targeted screening among case-patients with high-risk poultry exposures (e.g., a recent visit to a live bird market or close proximity to sick or dead poultry) may be a more efficient routine surveillance strategy for H5N1 virus in these types of settings.


Allopurinol improves endothelial dysfunction in chronic heart failure.
Increased oxidative stress in chronic heart failure is thought to contribute to endothelial dysfunction. Xanthine oxidase produces oxidative stress and therefore we examined whether allopurinol improved endothelial dysfunction in chronic heart failure. We performed a randomized, placebo-controlled, double-blind crossover study on 11 patients with New York Heart Association class II-III chronic heart failure, comparing 300 mg allopurinol daily (1 month) versus placebo. Endothelial function was assessed by standard forearm venous occlusion plethysmography with acetylcholine, nitroprusside, and verapamil. Plasma malondialdehyde levels were also compared to assess significant changes in oxidative stress. Allopurinol significantly increased the forearm blood flow response to acetylcholine (percentage change in forearm blood flow [mean+/-SEM]: 181+/-19% versus 120+/-22% allopurinol versus placebo; P=0.003). There were no significant differences in the forearm blood flow changes between the placebo and allopurinol treatment arms with regard to sodium nitroprusside or verapamil. Plasma malondialdehyde was significantly reduced with allopurinol treatment (346+/-128 nmol/L versus 461+/-101 nmol/L, allopurinol versus placebo; P=0.03), consistent with reduced oxidative stress with allopurinol therapy. We have shown that allopurinol improves endothelial dysfunction in chronic heart failure. This raises the distinct possibility that allopurinol might reduce cardiovascular events and even improve exercise capacity in chronic heart failure.


Assessment of Soiling on Highly Touched Clinical Surfaces in Intensive Care Units.
The aim of this study is to evaluate highly touched clinical surfaces using visual inspection methods and adenosine triphosphate by bioluminescence to identify soiling in intensive care units. Descriptive, cross-sectional study carried out in three intensive care units located in Belo Horizonte, MG, Brazil. Data collection included 142 assessments of environmental surfaces. For data analysis, the Pareto diagram and descriptive statistics were used through measures of central tendency. The visual inspection identified dirtiness in the infusion pump, alcohol dispenser, and telephone. The surface that showed a high level of contamination by organic matter identified by the adenosine triphosphate bioluminescence test was the telephone, with a median of 1012 RLU/cm2 (±348.8). The surface evaluation methods used in the intensive care units made it possible to identify dirt on surfaces highly touched by hands, reinforcing the need for investments in training and audits in the process of cleaning and disinfecting surfaces.


[A method of measuring cell orientation].
A method is described for measuring cell nuclei orientation in culture. The nuclear orientation in the experiment was compared with that obtained in the model experiment with electronic computer. The method developed allows to compare nuclear orientation in parts of culture which differ both by area and number of nuclei. The method can be modified for measuring cell nuclei orientation with reference to the substrate relief. Examples are given of the method's application for comparing orientation of mouse embryonic fibroblasts and cells of the strain L.


Cerebrolysin treatment attenuates heat shock protein overexpression in the brain following heat stress: an experimental study using immunohistochemistry at light and electron microscopy in the rat.
The possibility that overexpression of heat shock proteins (HSPs) in the CNS represents a neurodestructive signal following hyperthermia was examined in a rat model using a potent neuroprotective drug, Cerebrolysin (Ebewe Pharma, Austria). Rats subjected to four hours of heat stress in a biological oxygen demand incubator at 38 degrees C developed profound hyperthermia (41.23 +/- 0.14 degrees C) and overexpressed HSP 72 kD in several brain regions: cerebral cortex, hippocampus, cerebellum, thalamus, hypothalamus, brain stem, and spinal cord compared to controls. This HSP overexpression closely correlated with the leakage of blood-brain barrier permeability and vasogenic edema formation in these brain areas. HSP positive cells are largely confined in the edematous brain regions showing Evans blue leakage. Pretreatment with Cerebrolysin (5 mL/kg, i.v.) 30 minutes before heat stress markedly attenuated hyperthermia (39.48 +/- 0.23 degrees C, P < 0.01) and the induction of HSP to all the brain regions examined. Leakage of Evans blue albumin and increase in brain water content in these brain areas are also markedly reduced with Cerebrolysin pretreatment. These results are the first to show that Cerebrolysin, if administered before heat stress, attenuates hyperthermia induced stress reaction and HSP 72 kD induction. Taken together, these novel observations suggest that upregulation of HSP 72 kD in brain represents neurodestructive signals and a reduction in cellular stress mechanisms leading to decline in HSP expression is neuroprotective in nature.


The effects of aging and HIV disease on employment status and functioning.
As the prevalence of older adults living with HIV disease increases, questions are emerging regarding the extent to which older age amplifies the adverse effects of HIV on employment status and functioning. This cross-sectional study sought to (1) investigate the combined effects of HIV and older age on employment status, (2) identify clinicodemographic correlates of employment status among older HIV+ persons, and (3) examine the combined effects of HIV and age on workplace performance among employed participants. The sample was 358 HIV+ (163 older, 195 younger) and 193 HIV- (94 older, 99 younger) adults, who completed a comprehensive neurocognitive research assessment that included measures of employment status and current workplace functioning. We observed main effects of HIV and age on employment status, but no interaction. The older HIV+ sample demonstrated particularly high rates of disability, rather than elective retirement or unemployment. Among older HIV+ adults significant predictors of employment status included age, global neurocognitive functioning, combination antiretroviral therapy status, age at HIV infection, and hepatitis C coinfection. Finally, self-reported work functioning of older HIV+ adults differed only from the younger HIV- group. Findings suggest that older age and HIV disease have additive adverse effects on employment status, but not work functioning, and that employment status is associated with both neurocognitive and medical risk factors among older HIV+ adults. Further longitudinal research is needed to elucidate specific disease and demographic characteristics that may operate as protective factors for retaining gainful employment among older HIV+ adults. (PsycINFO Database Record


Localization, not important in all tumor-suppressing properties: a lesson learnt from scribble.
Aberrant localization of proteins is increasingly being suggested as a causal player in epithelial cancers. Despite this, few studies have investigated how mislocalization of a protein can alter individual biological processes that contribute to cancer progression. Using Ras as a model of transformation, we investigate how localization of the polarity protein Scribble contributes to its tumor-suppressive properties. Wild-type Scribble has been shown to modulate Ras-mitogen-activated protein kinase (MAPK) transformation both in vitro and in vivo. By utilizing a construct that carries a mutation in the LRR domain of Scribble (Scribble P305L) resulting in a cytosolic rather than the usual membrane-bound localization, we report that discrete tumor suppressive properties of Scribble are differentially sensitive to the localization of Scribble. We find that although the Scribble P305L mislocalization mutant can no longer suppress Ras-MAPK-induced invasion or epithelial to mesenchymal transition phenotypes, mislocalized Scribble can still suppress anchorage-independent cell growth. This study illustrates that the manner in which protein mislocalization contributes to cancer is likely complex and highlights the need for careful interrogation as to how cell polarity protein mislocalization, its secondary consequences, and the mutations that give rise to their mislocalization may contribute to specific aspects of cancer progression.


Carcinogenesis in relation to the stem-cell-mutation hypothesis.
From reports on fish, mice, rats, and humans, it can be concluded that at early developmental stages, especially stages before organogenesis, vertebrates are resistant to the induction of tumors by carcinogens. This conclusion and results on the molecular biology of chemical carcinogenesis in mice support the hypothesis that carcinogenesis of an organ is initiated by mutation of its stem cells formed during organogenesis. Convincing support for the existence of mutations that cause development of tumors is that heritable tumors are induced in mice and Drosophila by exposure of germ cells to radiation and chemicals. Various lines of evidence support the notion that tumor genes, which increase the predisposition of their carriers to develop tumors, are at least partly regulatory mutations. In this paper, the interrelation of tumorigenesis and teratogenesis, the high susceptibility of growing or regenerating organs to induction of tumors by carcinogens, and the latent period of induced neoplasms are discussed in relation to the stem-cell-mutation hypothesis.


Community-based health information technology alliances: potential predictors of early sustainability.
To determine potential predictors of sustainability among community-based organizations that are implementing health information technology (HIT) with health information exchange, in a state with significant funding of such organizations. A longitudinal cohort study of community-based organizations funded through the first phase of the $440 million Healthcare Efficiency and Affordability Law for New Yorkers program. We administered a baseline telephone survey in January and February 2007, using a novel instrument with open-ended questions, and collected follow-up data from the New York State Department of Health regarding subsequent funding awarded in March 2008. We used logistic regression to determine associations between 18 organizational characteristics and subsequent funding. All 26 organizations (100%) responded. Having the alliance led by a health information organization (odds ratio [OR] 11.4, P = .01) and having performed a community-based needs assessment (OR 5.1, P = .08) increased the unadjusted odds of subsequent funding. Having the intervention target the long-term care setting (OR 0.14, P = .03) decreased the unadjusted odds of subsequent funding. In the multivariate model, having the alliance led by a health information organization, rather than a healthcare organization, increased the odds of subsequent funding (adjusted OR 6.4; 95% confidence interval 0.8, 52.6; P = .08). Results from this longitudinal study suggest that both health information organizations and healthcare organizations are needed for sustainable HIT transformation.


Early combination of bromocriptine and levodopa in Parkinson's disease: a prospective randomized study of two parallel groups over a total follow-up period of 44 months including an initial 8-month double-blind stage.
To determine if the combination of levodopa (LD) plus bromocriptine (Br) in the early stages of Parkinson's disease (PD) permits reduction of LD dosage and consequently results in fewer motor fluctuations and dyskinesias, a double-blind, multicenter prospective study in 50 PD patients who had responded favorably to LD while under treatment with that drug for < or = 6 months was undertaken. Patients were randomized into two parallel groups (LD alone and LD plus Br). During the first placebo-controlled stage of the study lasting 8 months, association of a fixed dose of Br (15 mg/day) in the LD regimen did not allow a significant reduction in the daily LD dose. Still, in patients on combined LD plus Br, there was a tendency toward smaller daily requirements of LD as compared with those on LD alone, and the difference in LD dose between the two groups was significantly different (515.4 +/- 240 vs. 725.6 +/- 230 mg/day; p < 0.01) after 44 months of continuous treatment in the 40 patients still enrolled in the open-label stage. At that point in time, the mean dose of Br had been increased by 9.2 mg in the combined treatment group, and the mean dose of LD was 40.7% lower than in the group receiving LD alone. On subsequent evaluations, the number of patients with dyskinesias or describing wearing-off fluctuations severe enough to require changes in treatment was lower than in the group under combined therapy, the differences being significant after 20 and 44 months, respectively (36.8 vs. 9.5 and 47.3 vs. 14.2%). Our results support early combined LD-Br therapy in PD, but no conclusions can be drawn as to whether this dopamine agonist exerts a preventive effect on the late side effects of LD or has another mechanism of action.


Inhibitory dysfunction in frontotemporal dementia: a review.
Failure of inhibitory control is an early and consistent feature in patients suffering from frontotemporal dementia (FTD). This appears because of their pervasive ventromedial prefrontal atrophy-particularly in the orbitofrontal cortex-which has been linked to inhibitory dysfunction in studies on human and monkey lesions. However, the range of measures currently available to assess inhibitory processes in FTD is limited, and, as such, inhibitory dysfunction in FTD remains relatively underexplored. Subjective caregiver questionnaires are useful for defining disinhibition as it manifests behaviorally; however, endorsement of symptoms can vary largely across patients as it is contingent on the perceptiveness of the caregiver. The few objective neuropsychological tasks that tap directly into inhibitory functioning have potential, although they mostly rely on intact language and semantics, which can confound performance in FTD patients. An emergent possibility is to explore inhibitory functioning in FTD through nonverbal experimental tasks. Adaptation of such experimental tasks into clinical tools is a promising avenue for exploring one of the earliest behavioral features in FTD patients and concomitantly tap into their prevalent orbitofrontal cortex dysfunction. We suggest that improved characterization of early inhibitory dysfunction may facilitate more accurate diagnosis of FTD.


Kinetics of the Na+-H+ antiporter as assessed by the change in intracellular pH in MDCK cells.
The Na+-H+ antiporter regulates both H+ secretion and cell pH in renal epithelia. The present study was designed to further define the Na+ dependency and kinetics of proton efflux in MDCK cells. Intracellular pH (pHi) was determined with a pH-sensitive fluorescent probe, 2,7-bis-carboxyethyl-5,6-carboxyfluorescein (BCECF). Data were obtained from confluent monolayers grown on plastic cover slips and studied in media free of added CO2 and HCO-3, pH = 7.2 (pHo). Monolayers in NaCl maintain a pHi of 7.48 +/- 0.03 (n = 13). When cells were acidified with NH4Cl, pHi decreased to 6.73 +/- 0.07 (n = 10) and remained stable in Na+-free choline chloride. When monolayers were subsequently exposed to NaCl, pHi increased 0.28 +/- 0.04 pH units/min. Amiloride (2.5 mM) inhibited this Na+-dependent rise in pHi by more than 75%. The rate of pHi recovery after exposure to Na+ exhibited saturation kinetics; the apparent Km(Na) was 30.4 +/- 4.2 mM and maximum velocity was 107.1 +/- 17.1 delta [H+]i nmol X l-1 X min-1. We conclude that pHi regulation in the MDCK cell is in part mediated by a Na+-H+ antiporter, and the kinetics of this process can be reliably assessed by the pH-sensitive fluorometric probe, BCECF.


The relationship between motor performance and peer relations in 9- to 12-year-old children.
Poor motor skills have been associated with peer relationship difficulties, with lower peer preference and greater likelihood of suffering from withdrawal and low self-worth. Most research into these relationships has focused upon children with motor problems and on activities involving physical skills (play/sport). The current study examined the link between motor performance and peer relations in 9- to 12-year-old children in both physical and non-physical (schoolwork) settings using a community sample. Participants were 192 school children whose motor performance was tested using the Movement Assessment Battery for Children. Peer acceptance was assessed using the Peer Rating Scale and teachers completed the Peer Exclusion subscale of the Child Behaviour Scale to indicate each child's peer status. Children were also asked to indicate their level of physical activity and their perceived freedom in leisure using self-report questionnaires. Children with poor motor performance had lower levels of physical activity, and freedom in leisure and were less preferred by their peers in both play and classroom settings. These effects were stronger for boys than for girls. Teacher indicated that children with poorer motor skills experienced higher levels of peer rejection in the classroom setting. When motor performance was separated into fine- and gross-motor performance it was found that only the latter was significantly correlated with peer acceptance in the play context but that fine-motor skills contributed significantly to variance in teacher ratings of peer exclusion in the classroom setting. The results support and extend earlier findings that children with poor motor performance are less accepted by their peers in play settings and provide some support for this extending to settings involving low levels of physical activity (classroom settings). The results similarly support previous findings that motor performance is associated with perceived freedom in leisure and with the likelihood of participating in active pursuits.


Reconstruction of the regulatory network of Lactobacillus plantarum WCFS1 on basis of correlated gene expression and conserved regulatory motifs.
Gene regulatory networks can be reconstructed by combining transcriptome data from many different experiments to elucidate relations between the activity of certain transcription factors and the genes they control. To obtain insight in the regulatory network of Lactobacillus plantarum, microarray transcriptome data from more than 70 different experimental conditions were combined and the expression profiles of the transcriptional units (TUs) were compared. The TUs that displayed correlated expression were used to identify putative cis-regulatory elements by searching the upstream regions of the TUs for conserved motifs. Predicted motifs were extended and refined by searching for motifs in the upstream regions of additional TUs with correlated expression. In this way, cis-acting elements were identified for 41 regulons consisting of at least four TUs (correlation > 0.7). This set of regulons included the known regulons of CtsR and LexA, but also several novel ones encompassing genes with coherent biological functions. Visualization of the regulons and their connections revealed a highly interconnected regulatory network. This network contains several subnetworks that encompass genes of correlated biological function, such as sugar and energy metabolism, nitrogen metabolism and stress response.


LOX-1-Targeted Iron Oxide Nanoparticles Detect Early Diabetic Nephropathy in db/db Mice.
Activation of the low-density lipoprotein receptor 1 (LOX-1) contributes to pervasive inflammation in early diabetic nephropathy (DN). This study determined the feasibility of anti-LOX-1-ultrasmall superparamagnetic iron oxide nanoparticles (USPIOs) for noninvasive detection of inflammatory renal lesions in early DN. Anti-mouse LOX-1 antibody was conjugated to polyethyleneglycol-coated USPIOs. In vitro analysis of USPIOs uptake was performed in RAW264.7 macrophages. DN and control mice were imaged by MRI prior to and 24 h after contrast treatment. Anti-LOX-1 USPIOs were selectively taken up by macrophages, and kidney T2* MRI showed a lower signal intensity in the cortex of DN mice after 24 h administration of anti-LOX-1 USPIOs. Positive Perl's staining in DN lesions, indicating the presence of iron oxide, was consistent with immunohistochemistry indicating the presence of LOX-1 and CD68. This report shows that anti-LOX-1 USPIOs detect LOX-1-enriched inflammatory renal lesions in early DN mice. Our study provides important information for characterizing and monitoring early DN.


Recurrent toxocariasis due to chronic urticaria and successful treatment with prolonged albendazole therapy.
Toxocariasis is a worldwide human helminthiasis, especially seen in temperate and tropical climate regions around the world. The diagnosis of this disease is performed on the basis of clinical symptoms and laboratory findings. Albendazole is one of the treatment choices for toxocariasis, with a currently recommended regimen of 10 mg/kg/day in two doses (400 mg twice daily) for 5 days. However, there is no precise consensus about the duration of the treatment. In this article, we report a case of toxocariasis; the patient visited our infectious disease polyclinic with complaints of long-term itching and urticarial skin lesions that were resistant to routine treatment and that recurred. Then, recurrent disease was resolved and skin lesions were diminished after prolonged albendazole therapy.


Confronting AIDS in older adults.
A 57-year-old corporate executive, married with three grown children, began suffering from severe flu-like symptoms and weight loss. Hospitalized for a week, he was tested for chronic fatigue syndrome and mononucleosis. Finally, with no change in his symptoms, his physician recommended an HIV test. The results were positive.


Dexamethasone modulation of gestation length and parturition in rats.
Dexamethasone blocks aromatase and phospholipase A2 enzyme activities that are essentially involved in the formation of oestrogens and prostaglandins, the key chemicals to initiate parturition. The present study was undertaken to determine whether dexamethasone, a potent glucocorticoid, could prolong gestation and/or delay parturition in rats. Dexamethasone at 0.5 mg/rat/day from Day 19 through Day 21 of pregnancy consistently prolonged gestation. Only 36% of the pregnant rats had labour with an extended parturition time. Foetal mortality rate was also high. The remaining 64% pregnant rats that did not deliver showed intrauterine foetal death and resorption. Concomitant injection of oestradiol cyclopentylpropionate or prostaglandin F2 alpha on Day 19 effectively reversed the deleterious effects of dexamethasone. 100% of the pregnant rats had successful labour at term. The parturition time and foetal mortality rate were not different from controls. The results, therefore, indicate that an excess glucocorticoid that initiates parturition in sheep conversely prolongs gestation and delays parturition in rats.


Agnogene deletion in a novel pathogenic JC virus isolate impairs VP1 expression and virion production.
Infection of glial cells by the human polyomavirus JC (JCV) causes progressive multifocal leukoencephalopathy (PML). JCV Encephalopathy (JCVE) is a newly identified disease characterized by JCV infection of cortical pyramidal neurons. The virus JCVCPN associated with JCVE contains a unique 143 base pair deletion in the agnogene. Contrary to most JCV brain isolates, JCVCPN has an archetype-like regulatory region (RR) usually found in kidney strains. This provided us with the unique opportunity to determine for the first time how each of these regions contributed to the phenotype of JCVCPN. We characterized the replication of JCVCPN compared to the prototype virus JCVMad-1 in kidney, glial and neuronal cell lines. We found that JCVCPN is capable of replicating viral DNA in all cell lines tested, but is unable to establish persistent infection seen with JCVMad-1. JCVCPN does not have an increased ability to replicate in the neuronal cell line tested. To determine whether this phenotype results from the archetype-like RR or the agnogene deletion, we generated chimeric viruses between JCVCPN of JCVMad-1. We found that the deletion in the agnogene is the predominant cause of the inability of the virus to maintain a persistent infection, with the introduction of a full length agnogene, either with or without agnoprotein expression, rescues the replication of JCVCPN. Studying this naturally occurring pathogenic variant of JCV provides a valuable tool for understanding the functions of the agnogene and RR form in JCV replication.


Is heparin a placental anticoagulant in high-risk pregnancies?
Randomized control trials show beneficial effects of heparin in high-risk pregnancies to prevent preeclampsia and intrauterine growth restriction. However, the lack of placental pathology data in these trials challenges the assumption that heparin is a placental anticoagulant. Recent data show that placental infarction is probably associated with abnormalities in development of the placenta, characterized by poor maternal perfusion and an abnormal villous trophoblast compartment in contact with maternal blood, than with maternal thrombophilia. At-risk pregnancies may therefore be predicted by noninvasive prenatal testing of placental function in mid-pregnancy. Heparin has diverse cellular functions that include direct actions on the trophoblast. Dissecting the non-anticoagulant actions of heparin may indicate novel and safer therapeutic targets to prevent the major placental complications of pregnancy.


Lack of humoral immune protection against Treponema denticola virulence in a murine model.
This study investigated the characteristics of humoral immune responses to Treponema denticola following primary infection, reinfection, and active immunization, as well as immune protection in mice. Primary infection with T. denticola induced a significant (400-fold) serum immunoglobulin G (IgG) response compared to that in control uninfected mice. The IgG response to reinfection was 20, 000-fold higher than that for control mice and 10-fold higher than that for primary infection. Mice actively immunized with formalin-killed treponemes developed serum antibody levels seven- to eightfold greater than those in animals after primary infection. Nevertheless, mice with this acquired antibody following primary infection or active immunization demonstrated no significant alterations of lesion induction or decreased size of the abscesses following a challenge infection. Mice with primary infection developed increased levels of IgG3, IgG2b, and IgG2a antibodies, with IgG1 being lower than the other subclasses. Reinfected mice developed enhanced IgG2b, IgG2a, and IgG3 and less IgG1. In contrast, immunized mice developed higher IgG1 and lower IgG3 antibody responses to infection. These IgG subclass distributions indicate a stimulation of both Th1 and Th2 activities in development of the humoral immune response to infection and immunization. Our findings also demonstrated a broad antigen reactivity of the serum antibody, which was significantly increased with reinfection and active immunization. Furthermore, serum antibody was effective in vitro in immobilizing and clumping the bacteria but did not inhibit growth or passively prevent the treponemal infection. These observations suggest that humoral immune responses, as manifested by antibody levels, isotype, and antigenic specificity, were not capable of resolving a T. denticola infection.


A Robust Observer-Based Control Strategy for n-DOF Uncertain Robot Manipulators with Fixed-Time Stability.
In this paper, a robust observer-based control strategy for n-DOF uncertain robot manipulators with fixed-time stability was developed. The novel fixed-time nonsingular sliding mode surface enables control errors to converge to the equilibrium point quickly within fixed time without singularity. The development of the novel fixed-time disturbance observer based on a uniform robust exact differentiator also allows uncertain terms and exterior disturbances to be proactively addressed. The designed observer can accurately approximate uncertain terms within a fixed time and contribute to significant chattering reduction in the traditional sliding mode control. A robust observer-based control strategy was formulated, according to a combination of the fixed-time nonsingular terminal sliding mode control method and the designed observer, to yield global fixed time stability for n-DOF uncertain robot manipulators. The proposed controller proved definitively that it was able to obtain global stabilization in fixed time. The approximation capability of the proposed observer, the convergence of the proposed sliding surface, and the effectiveness of the proposed control strategy in fixed time were fully confirmed by simulation performance on an industrial robot manipulator.


Curved reconstruction along the anterior optic pathway.
Curved reconstruction of a three-dimensional data set along the anterior optic pathway improves visibility of the optic nerves and chiasm and facilitates comparison between the two nerves. Curved reconstruction reveals three patterns in patients with masses of the anterior optic pathway. Retrobulbar buckling of the optic nerve into a "periscope" configuration is observed in some patients.


Particle-assisted semidirect breath figure method: a facile way to endow the honeycomb-structured petri dish with molecular recognition capability.
Recently, we have developed a semidirect breath figure (sDBF) method for direct fabrication of large-area and ordered honeycomb structures on commercial polystyrene (PS) Petri dishes without the use of an external polymer solution. In this work, we showed that both the pore size and the pore uniformity of the breath figure patterns were controllable by solvent amount. The cross-sectional image shows that only one layer of pores was formed on the BF figure patterns. By combing the sDBF method and Pickering emulsion and using the modular building blocks, we endowed the honeycomb-structured Petri dish with molecular recognition capability via the decoration of molecularly imprinted polymer (MIP) nanoparticles into the honeycomb pores. The radioligand binding experiments show that the MIP nanoparticles on the resultant honeycomb structures maintained high molecular binding selectivity. The reusability study indicates that MIP-BF patterns had excellent mechanical stability during the radioligand binding process. We believe that the modular approach demonstrated in this work will open up further opportunities for honeycomb structure-based chemical sensors for drug analysis, substrates for catalysts, and scaffold for cell growth.


Identification of positionally distinct astrocyte subtypes whose identities are specified by a homeodomain code.
Astrocytes constitute the most abundant cell type in the central nervous system (CNS) and play diverse functional roles, but the ontogenetic origins of this phenotypic diversity are poorly understood. We have investigated whether positional identity, a fundamental organizing principle governing the generation of neuronal subtype diversity, is also relevant to astrocyte diversification. We identified three positionally distinct subtypes of white-matter astrocytes (WMA) in the spinal cord, which can be distinguished by the combinatorial expression of Reelin and Slit1. These astrocyte subtypes derive from progenitor domains expressing the homeodomain transcription factors Pax6 and Nkx6.1, respectively. Loss- and gain-of-function experiments indicate that the positional identity of these astrocyte subtypes is controlled by Pax6 and Nkx6.1 in a combinatorial manner. Thus, positional identity is an organizing principle underlying astrocyte, as well as neuronal, subtype diversification and is controlled by a homeodomain transcriptional code whose elements are reutilized following the specification of neuronal identity earlier in development.


Interactive MR imaging-guided biopsy and aspiration with a modified clinical C-arm system.
This investigation was performed to test the hypotheses that interactive guidance of MR image acquisition during needle-directed procedures using a clinical 0.2-T C-arm open MR imaging system integrated with a frameless optically linked stereotaxy system is feasible, and that procedure times can be sufficiently short to be well tolerated by the patient. One hundred six MR-guided procedures were performed in 86 patients (ranging in age from 5 months to 88 years) using a clinical C-arm imaging system supplemented with an in-room RF-shielded liquid crystal display monitor, a frameless stereotaxy system, rapid gradient-echo sequences for needle guidance, and MR-compatible monitoring and surgical lighting equipment. We performed 50 biopsies and aspirations of the head and neck in 37 patients, 23 biopsies of musculoskeletal lesions in 22 patients, 16 biopsies of abdominal sites in 10 patients, six biopsies of the thoracolumbar spine or sacrum in six patients, and 11 shoulder joint injections for MR arthrography in 11 patients, in addition to 38 MR arthrographic injections on the same imaging system described in a previous report. Tissue sampling included fine-needle aspiration (n = 90) and cutting needle core biopsy (n = 41). Thirty-five patients underwent both procedures. Procedures were evaluated for success of needle placement, procedure time, and complications. Needle placement was successful in all cases, and no complications occurred. Tissue was sufficient for pathologic diagnosis for all but eight patients. Passes per patient averaged 2.1. For fine-needle aspiration, instrument time averaged 7 min 42 sec per pass, cutting needle core biopsy averaged 6 min 24 sec, and shoulder injection averaged 8 min. MR imaging guidance for needle procedures on a clinical 0.2-T C-arm system with supplemental interventional accessories is feasible, with relatively rapid needle placement.


Somatic antigens of Streptococcus group E. I. Comparison of extraction techniques.
Eleven Streptococcus group E strains, representing serotypes I, II, III, IV, V, and "untypable" isolates, were extracted by formamide, trichloroacetic acid, and hydrochloric acid under various conditions in an effort to determine the best method for recovering maximum amounts of group and type antigens. The group antigen was found to be relatively stable, and adequate amounts for identification purposes were recovered by a wide spectrum of conditions. Type-specific antigens were relatively labile, and were destroyed at low pH in acid hydrolysis or by prolonged heating in formamide hydrolysis. The best single procedure for recovering both type and group antigens from Streptococcus group E was formamide hydrolysis for 30 min at 180 C.


Structures, thermodynamics and dynamics of topological defects in Gay-Berne nematic liquid crystals.
Topological defects are a ubiquitous phenomenon across different physical systems. A better understanding of defects can be helpful in elucidating the physical behaviors of many real materials systems. In nematic liquid crystals, defects exhibit unique optical signatures and can segregate impurities, showing their promise as molecular carriers and nano-reactors. Continuum theory and simulations have been successfully applied to link static and dynamical behaviors of topological defects to the material constants of the underlying nematic. However, further evidence and molecular details are still lacking. Here we perform molecular dynamics simulations of Gay-Berne particles, a model nematic, to examine the molecular structures and dynamics of +1/2 defects in a thin-film nematic. Specifically, we measure the bend-to-splay ratio K3/K1 using two independent, indirect measurements, showing good agreement. Next, we study the annihilation event of a pair of ±1/2 defects, of which the trajectories are consistent with experiments and hydrodynamic simulations. We further examine the thermodynamics of defect annihilation in an NVE ensemble, leading us to correctly estimate the elastic modulus by using the energy conservation law. Finally, we explore effects of defect annihilation in regions of nonuniform temperature within these coarse-grained molecular models which cannot be analysed by existing continuum level simulations. We find that +1/2 defects tend to move toward hotter areas and their change of speed in a temperature gradient can be quantitatively understood through a term derived from the temperature dependence of the elastic modulus. As such, our work has provided molecular insights into structures and dynamics of topological defects, presented unique and accessible methods to measure elastic constants by inspecting defects, and proposed an alternative control parameter of defects using temperature gradient.


Measurement of mie scattering intensities from monodispersed spherical particles as a function of wavelength.
Mie scattering intensities as a function of the size parameter are measured by use of a tunable dye laser and monodispersed spherical particles. The experimental results are compared with the Mie single scattering theory; a discrepancy in the exact position of the maxima and minima was detected. Agreement between experiment and theory was improved by applying a correction to the manufacturer's index of refraction function for the particles.


Treatment of spontaneous esophageal rupture (Boerhaave syndrome) using thoracoscopic surgery and sivelestat sodium hydrate.
The mortality rate of spontaneous esophageal rupture remains 20% to 40% due to severe respiratory failure. We have performed thoracoscopic surgery for esophageal disease at our department since 1994. Sivelestat sodium hydrate reportedly improves the pulmonary outcome in the patients with acute lung injury (ALI). We retrospectively evaluated the usefulness of thoracoscopic surgery and perioperative administration of sivelestat sodium hydrate for spontaneous esophageal rupture in 12 patients who underwent thoracoscopy at our department between 2002 and 2014. The patient cohort included 11 males and one female (median age, 61 years). The lower left esophageal wall was perforated in all patients. Surgical procedures consisted of thoracoscopic suture and thoracic drainage in six patients, transhiatal suture and thoracoscopic thoracic drainage in five, and thoracoscopic esophagectomy and thoracic drainage in one. The median time from onset to surgery was 8 hours with a surgical duration of 210 minutes, blood loss 260 mL, postoperative ventilator management 1 day, intensive care unit (ICU) stay 5 days, and interval to restoration of oral ingestion 13 days. Postoperative complications included respiratory failure in four patients, pyothorax in three, and leakage in one. There was no instance of perioperative mortality. Regarding perioperative administration of sivelestat sodium hydrate, the postoperative arterial oxygen partial pressure-to-fractional inspired oxygen ratio (P/F) and C-reactive protein (CRP) levels in the administration group were significantly better than those in the non-administration group on postoperative days 4 (P=0.035) and 5 (P=0.037), respectively. In contrast, there was no significant difference between the groups in median time of ventilator management, ICU stay, oral ingestion following surgery, or hospital stay. Thoracoscopic surgery obtained acceptable results in all patients, including two with a significant time elapse from onset to treatment. Furthermore, sivelestat sodium hydrate was suggested to help improve postoperative respiration and inflammatory response.


Enzyme mediated site-specific surface modification.
Stable tethering of bioactive peptides like RGD to surfaces can be achieved via chemical bonding, biotin streptavidin interaction, or photocross-linking. More challenging is the immobilization of proteins, since methods applied to immobilize peptides are either not specific or versatile enough or might even compromise the protein's bioactivity. To overcome this limitation, we have employed a scheme that by enzymatic (transglutaminase) reaction allows the site-directed and site-specific coupling of growth factors and other molecules to nonfouling poly(L-lysine)-graft-poly(ethylene glycol) (PLL-g-PEG) coated surfaces under physiological conditions. By our modular and flexible design principle, we are able to functionalize these surfaces directly with peptides and growth factors or precisely position poly(ethylene glycol) (PEG)-like hydrogels for the presentation of growth factors as exemplified with vascular endothelial growth factor (VEGF).


Mammalian cytochrome b.
Digestion of a preparation of cytochromes b and c(1) with pancreatic protease followed by ammonium sulfate precipitation resulted in a soluble cytochrome b uncontaminated by cytochrome C(l). This preparation, which was free of succinic dehydrogenase and cytochrome oxidase activity, had an estimated deltaE(1 cm)(1g/ml) of 102 for its alpha-peak. In the reduced form absorption maxima were found at 560 to 562, 530 to 532, and 427 to 428 mmicro, and in the oxidized form, at 413 mmicro.


Pilot Study Measuring the Novel Satiety Hormone, Pro-Uroguanylin, in Adolescents With and Without Obesity.
Disruption of satiety signaling may lead to increased caloric intake and obesity. Uroguanylin, the intestinal hormone, travels as a precursor to the central nervous system where it activates guanylyl cyclase C and stimulates pro-satiety neurons. Rodent studies have demonstrated that guanylyl cyclase C-knockout mice overeat and have increased weight gain versus wild-type mice and hyper-caloric obesity diminishes uroguanylin expression. We measured circulating plasma pro-uroguanylin, along with other gastrointestinal peptides and inflammatory markers, in human adolescents with and without obesity, as a pilot study. We hypothesized that adolescents with obesity would have less circulating pro-uroguanylin than adolescents without obesity have. We recruited 24 adolescents (age 14-17 years) with and without obesity (body mass index >95% or body mass index <95%) and measured plasma pro-uroguanylin at fasting and successive time points after a meal. We measured 3 other satiety hormones and 2 inflammatory markers to characterize overall satiety signaling and highlight any link between uroguanylin and inflammation. Female adolescents with obesity had lower circulating pro-uroguanylin levels than female adolescents without obesity; we observed no difference in males. Other measured gastrointestinal peptides varied in their differences between cohorts. Inflammatory markers were higher in female participants with obesity. In adolescents with and without obesity, we can measure circulating pro-uroguanylin levels. In female adolescents without obesity, levels are particularly higher. Pro-uroguanylin secretion patterns differ from other circulating gastrointestinal peptides. In female adolescents with obesity, inflammation correlates with decreased pro-uroguanylin levels.


Disruption of the CD40-CD40 ligand system prevents an oxygen-induced respiratory distress syndrome.
Oxygen therapy is a mainstay treatment for infants and adults with poor lung function. Unfortunately, oxygen itself is toxic and incites respiratory cell damage and inflammation. Therapies for oxygen-induced lung damage are nonexistent. Employing a mouse model of hyperoxic lung injury, a monoclonal anti-CD40 ligand (L) antibody (MR1), which disrupts CD40-CD40L interactions, was tested for the ability to reduce pulmonary injury. Intraperitoneal administration of MR1, either before or after oxygen exposure, was remarkably effective in reducing and in many cases preventing lung injury. The pro-inflammatory enzyme cyclooxygenase-2 (Cox-2), responsible for prostaglandin production, is massively up-regulated in the lungs after hyperoxic exposure. Immunohistochemical staining for Cox-2 revealed that MR1 greatly reduces the oxygen-induced induction of Cox-2. The remarkable effectiveness of MR1 in blunting hyperoxic lung injury in this preclinical model may be relevant to the hundreds of thousands of patients who require treatment with high oxygen and who are at risk for developing severe pulmonary inflammation and consequent fibrosis. Strategies to disrupt CD40-CD40L interactions may offer a new mode of intervention for oxygen-induced acute respiratory distress syndrome and other inflammatory lung disorders.


Odontohypophosphatasia: report of two cases.
Reports of a mild form of hypophosphatasia have been presented in which the oral findings were the only clinical and radiographic manifestations of the disease. It is important to support the clinical interpretations with laboratory findings in order to make a differential diagnosis from such diseases as Papillon-LeFevre Syndrome and cyclic diseases and noncyclic neutropenia. The term odontohypophosphatasia is suggested in those cases where the dental findings are the predominant manifestations of the disease.


A simple thermodilution technique to assess coronary endothelium-dependent microvascular function in humans: validation and comparison with coronary flow reserve.
To validate a novel method for assessment of coronary endothelium-dependent microvascular function and compare this index with the adenosine-derived coronary flow reserve (CFR). We validated use of intra-coronary pressure wire-derived thermodilution to assess changes in coronary flow compared to Doppler flow-wire/quantitative coronary angiography- (QCA) derived data in response to the endothelial agonist substance-P (endothelium-dependent response). There was a close correlation between Doppler/QCA- and thermodilution-derived assessment of endothelium-dependent microvascular function (r = 0.76; P < 0.001). Next, pressure wire-based thermodilution was employed to sequentially compare CFR (hyperaemia achieved with adenosine-140 microg/kg/mL) with changes in coronary flow in response to substance-P (20 pmol/min intra-coronary infusion; 2 min) in 65 unobstructed coronary arteries. There was no correlation between CFR and coronary endothelium-dependent microvascular response (r = 0.08; P = 0.50). Both indices were in turn compared with clinical markers of endothelial dysfunction, namely Framingham risk score (FRS-a marker for cardiovascular risk factor clustering, hence an indirect clinical measure of endothelial dysfunction) and presence/absence of diabetes. Patient's FRS correlated with coronary endothelium-dependent microvascular response (r = -0.48; P < 0.001), but not with CFR (r = 0.14; P = 0.25). Diabetic patients had greater endothelial dysfunction than non-diabetics (P < 0.001) whereas CFR was not influenced by diabetes (P = 0.10). A simple pressure wire-based thermodilution technique can be used to assess coronary endothelium-dependent microvascular function. Adenosine-derived CFR does not adequately interrogate the endothelium-dependent component of coronary microvascular function.


Wild mouse variants of envelope genes of xenotropic/polytropic mouse gammaretroviruses and their XPR1 receptors elucidate receptor determinants of virus entry.
Mouse xenotropic and polytropic leukemia viruses (XMVs and PMVs) are closely related gammaretroviruses that use the XPR1 receptor for entry. To identify amino acid residues in XPR1 important for virus entry, we tested mouse cells derived from evolutionarily divergent species for susceptibility to prototypical PMVs, XMVs, and the wild mouse isolate CasE#1. CasE#1 has a variant XMV/PMV host range, and sequence analysis of the CasE#1 env gene identifies segments related to PMVs and XMVs. Cells from the Asian mouse species Mus pahari show a unique pattern of susceptibility to these three viruses; these cells are susceptible to XMVs and CasE#1 but are resistant to PMVs, whereas NIH 3T3 cells show the reciprocal pattern, susceptibility to only PMVs. The M. pahari XPR1 gene differs from that of NIH 3T3 in the two extracellular loops (ECLs) previously shown to mediate virus entry (M. Marin, C. S. Tailor, A. Nouri, S. L. Kozak, and D. Kabat, J. Virol. 73:9362-9368, 1999, and N. S. Van Hoeven and A. D. Miller, Retrovirology 2:76, 2005). Using transfected hamster cells expressing chimeric and mutated XPR1s, we demonstrated that the susceptibility differences between NIH 3T3 and M. pahari cells are receptor mediated, that PMV entry requires residues in ECL3, that the CasE#1 entry determinant is in ECL4, and that determinants for XMV entry are in both ECL3 and ECL4. Additional substitutions in ECL3 and ECL4 modulate virus susceptibility and suggest that ECL3 and ECL4 may contribute to the formation of a single virus receptor site. The position of M. pahari at the base of the Mus phylogenetic tree indicates that XPR1-mediated susceptibility to XMVs is the ancestral type in this genus and that the phenotypic variants of mouse XPR1 likely arose in conjunction with exposure to gammaretrovirus infections and coevolutionary adaptations in the viral envelope.


Evaluation of the olfactory bulb volume and morphology in patients with coronavirus disease 2019: can differences create predisposition to anosmia?
This study aimed to investigate whether the volume and morphology of the olfactory bulb are effective in the occurrence of anosmia in patients after COVID-19 infection. The olfactory bulbus volume was calculated by examining the brain magnetic resonance imaging of cases with positive (+) COVID-19 polymerase chain reaction test with and without anosmia. Evaluated magnetic resonance imaging images were the scans of patients before they were infected with COVID-19. The olfactory bulbus and olfactory nerve morphology of these patients were examined. The brain magnetic resonance imaging of 59 patients with anosmia and 64 controls without anosmia was evaluated. The olfactory bulb volumes of both groups were calculated. The olfactory bulb morphology and olfactory nerve types were examined and compared between the two groups. The left and right olfactory bulb volumes were calculated for the anosmia group and control group as 47.8±15/49.3±14.3 and 50.5±9.9/50.9±9.6, respectively. There was no statistically significant difference between the two groups. When the olfactory bulb morphology was compared between the two groups, it was observed that types D and R were dominant in the anosmia group (p<0.05). Concerning olfactory nerve morphology, type N was significantly more common in the control group (p<0.05). According to our results, the olfactory bulb volume does not affect the development of anosmia after COVID-19. However, it is striking that the bulb morphology significantly differs between the patients with and without anosmia. It is clear that the evaluation of COVID-19-associated smell disorders requires studies with a larger number of patients and a clinicoradiological approach.


How does theory compare to experiment for oscillator strengths in electronic spectra? Proposing range-separated hybrids with reliable accountability.
As an important quantity in atomic and molecular spectroscopy, oscillator strength should be mentioned. Oscillator strength is linked to the transition dipole moment and consequently to the transition probability between two states, where its magnitude is directly connected to the intensity of the peaks in ultraviolet-visible spectra. However, accurately accounting for oscillator strengths still remains one of the greatest challenges in theory and experiment. Given previous efforts in the context of investigations into oscillator strengths, the related theoretical treatments are relatively limited and have proven to be challenging. In this work, the oscillator strengths in the electronic spectra of organic compounds have thoroughly been investigated with the help of optimally tuned range-separated hybrids (OT-RSHs). In particular, variants of the OT-RSHs combined with the polarizable continuum model (PCM), OT-RSHs-PCM, as well as their screened versions accounting for the screening effects by the electron correlation through the dielectric constant, OT-SRSHs-PCM, are proposed for reliable prediction of the oscillator strengths. The role of the involved ingredients in the proposed methods, namely the underlying density functional approximations, short-range and long-range Hartree-Fock (HF) exchange, as well as the range-separation parameter, has been examined in detail. It is shown that any combination of the parameters in the proposed approximations does not render the reliable oscillator strengths, but a particular compromise among them is needed to describe the experimental data well. Perusing all the results of our developed methods, the best ones are found to be the generalized gradient approximation-based OT-RSHs-PCM, coupled with the linear response theory in the non-equilibrium solvation regime, with the correct asymptotic behavior and incorporating no (low) HF exchange contributions in the short-range part. The best proposed approximations also reveal superior performances not only with respect to their standard counterparts with the default parameters but also as compared to earlier range-separated functionals. Finally, the applicability of the best approximation is also put into broader perspective, where it is used for predicting the oscillator strengths in other sets of compounds not included in the process of developing the approximations. Hopefully, our proposed method can function as an affordable alternative to the expensive wave function-based methods for both theoretical modeling and confirming the experimental observations in the field of electronic spectroscopy.


Potential of milk-derived bioactive peptides as antidiabetic, antihypertensive, and xanthine oxidase inhibitors: a comprehensive bibliometric analysis and updated review.
Bioactive peptides consist of small protein fragments, which are inactive in their original conformation, and they become active when released from these through enzymatic hydrolysis or fermentation processes. The bioactivity of such peptides has been extensively reported in the literature as contributors to organic homeostasis processes, as well as in immunomodulation, organism defense against oxidative processes, among others. In this study, reports of the activity of BPs isolated from milk with the potential glycemic control, antihypertensive activity, and inhibitors of uric acid formation were compiled. A systematic literature review and bibliometric analysis were conducted, using the PICO strategy for the research. The temporal analysis of publications revealed a growing interest in the investigation of bioactive peptides with potential antidiabetic, antihypertensive, and xanthine oxidase inhibitory activities, using dairy sources as products for their extraction. The literature analysis also revealed an increase in research involving non-bovine dairy products for bioactive peptide extraction. The collaboration network among authors exhibited weaknesses in scientific cooperation. Regarding the analysis of keywords, the usage of terms such as "bioactive peptides", "antioxidant", "antihypertensive", and "diabetes" was evident, constituting the main research clusters. Peptides with low molecular weight, typically < 10 kDa, of hydrophobic nature with aliphatic and aromatic chains, have significant implications in molecular interactions for the required activities. Although there is a growing interest in the industry regarding the utilization of bioactive peptides as potential drugs, there is a need to address gaps related to elucidating their interactions with cellular targets and their use in human therapy.


Combined oral and enema treatment with Pentasa (mesalazine) is superior to oral therapy alone in patients with extensive mild/moderate active ulcerative colitis: a randomised, double blind, placebo controlled study.
Oral aminosalicylates are well established in the treatment of active mild/moderate ulcerative colitis (UC) when the disease is extensive (that is, beyond the splenic flexure). The majority of clinical symptoms relate to disease activity in the distal part of the colon and therefore this study was designed to investigate if adding a mesalazine enema to oral mesalazine has additional benefit for patients with extensive mild/moderate active UC. A randomised double blind study was performed in 127 ambulatory patients. All received 4 g/day (twice daily dosing) oral mesalazine for eight weeks. During the initial four weeks, they additionally received an enema at bedtime containing 1 g of mesalazine or placebo. Disease activity was assessed using the ulcerative colitis disease activity index, with clinical and endoscopic signs at four and eight weeks. Remission was obtained in 44% (95% confidence interval (CI) 31%, 58%) of the mesalazine enema group (Me) and in 34% (95% CI 21%, 49%) of the placebo enema group (Pl) at four weeks (p = 0.31) and in 64% (95% CI 50%, 76%) of the Me group versus 43% (95% CI 28%, 58%) of the Pl group at eight weeks (p = 0.03). Improvement was obtained in 89% (95% CI 78%, 96%) of the Me group versus 62% (95% CI 46%, 75%) of the Pl group at four weeks (p = 0.0008) and in 86% (95% CI 75%, 94%) of the Me group versus 68% (95% CI 53%, 81%) of the Pl group at eight weeks (p = 0.026). In patients with extensive mild/moderate active UC, the combination therapy is superior to oral therapy. It is safe, well accepted, and may be regarded as firstline treatment.