Influence of ambient temperature and drug treatments on brain oedema induced by impact injury on skull in rats.
The progression and persistence of oedema development following impact-injury on closed skull was studied in anaesthetised as well as in unanaesthetised rats. The degree and rate of oedema development, following trauma, was aggravated in anaesthetised hypothermic animals but was reduced/or delayed by maintenance of body temperature at euthermic level. In general, the unanaesthetised animals showed a greater accumulation of oedema fluid than the corresponding anaesthetised group. The development of oedema corresponded more or less with the accumulation of 5-HT level in plasma and brain. This development of oedema was completely prevented following pretreatment with p-CPA, indomethacin paracetamol and aminophylline in unanaesthetised animals; whereas these drugs were able only to partially reduce the oedema development in euthermic anaesthetised animals. On the other hand the cyproheptadine pretreatment aggravated the oedema development which was more pronounced in unanaesthetised animals. The probable mechanism of the action of these drugs has been discussed.


Development and Degeneration of Retinal Ganglion Cell Axons in Xenopus tropicalis.
Neurons make long-distance connections via their axons, and the accuracy and stability of these connections are crucial for brain function. Research using various animal models showed that the molecular and cellular mechanisms underlying the assembly and maintenance of neuronal circuitry are highly conserved in vertebrates. Therefore, to gain a deeper understanding of brain development and maintenance, an efficient vertebrate model is required, where the axons of a defined neuronal cell type can be genetically manipulated and selectively visualized in vivo. Placental mammals pose an experimental challenge, as time-consuming breeding of genetically modified animals is required due to their in utero development. Xenopus laevis, the most commonly used amphibian model, offers comparative advantages, since their embryos ex utero during which embryological manipulations can be performed. However, the tetraploidy of the X. laevis genome makes them not ideal for genetic studies. Here, we use Xenopus tropicalis, a diploid amphibian species, to visualize axonal pathfinding and degeneration of a single central nervous system neuronal cell type, the retinal ganglion cell (RGC). First, we show that RGC axons follow the developmental trajectory previously described in X. laevis with a slightly different timeline. Second, we demonstrate that co-electroporation of DNA and/or oligonucleotides enables the visualization of gene function-altered RGC axons in an intact brain. Finally, using this method, we show that the axon-autonomous, Sarm1-dependent axon destruction program operates in X. tropicalis. Taken together, the present study demonstrates that the visual system of X. tropicalis is a highly efficient model to identify new molecular mechanisms underlying axon guidance and survival.


The Genetic Basis of Natural Variation in Kernel Size and Related Traits Using a Four-Way Cross Population in Maize.
Kernel size is an important component of grain yield in maize breeding programs. To extend the understanding on the genetic basis of kernel size traits (i.e., kernel length, kernel width and kernel thickness), we developed a set of four-way cross mapping population derived from four maize inbred lines with varied kernel sizes. In the present study, we investigated the genetic basis of natural variation in seed size and other components of maize yield (e.g., hundred kernel weight, number of rows per ear, number of kernels per row). In total, ten QTL affecting kernel size were identified, three of which (two for kernel length and one for kernel width) had stable expression in other components of maize yield. The possible genetic mechanism behind the trade-off of kernel size and yield components was discussed.


Use of glycosylated hemoglobins in the long-term management of diabetes.
Glycosylated hemoglobin levels are a reflection of a patient's average blood sugar for the two preceding months. Knowing a patient's glycosylated hemoglobin levels better equips a health care practitioner to manage the patient's diabetes and thus helps forestall diabetic complications. This test gives an estimation of what the patient has been eating for the past several weeks and how well the patient has been adhering to the medication regimen, not just how well the patient has prepared for the office visit. The use of glycosylated hemoglobins should motivate patients with diabetes to maintain higher degrees of control and help practitioners work with patients on their treatment programs. Advantages to using glycosylated hemoglobin levels include the patient need not fast prior to the test; the test is not affected by recent physical and/or emotional fluctuations; and the test may be performed on anyone at any time without prior instructions. Nurse practitioners in primary health care roles are in excellent positions to use glycosylated hemoglobin levels and evaluate their effectiveness in managing diabetes.


Selection for weaning weight in Targhee sheep in two environments. I. Direct response.
In 1961, selection for 120-d weight was initiated in two flocks from a common base population of grade Targhee sheep. At Davis, sheep were maintained on a good plane of nutrition, on irrigated pasture or in drylot. At Hopland, sheep grazed annual grassland range, with supplementary feeding only at mating and lambing. Selected (DW) and control (DC) lines were maintained at Davis from 1961 through 1977. A selected (HW) line, replicate control (HC1 and HC2) lines and a line (DH) mated to the Davis DW rams were maintained at Hopland from 1961 through 1980, with the exception that HC2 was terminated in 1977. Multiplicative factors were used to adjust weights for effects of age of dam, sex and type of birth and rearing. Response to selection was estimated as the difference between selected and control line linear regression coefficients of adjusted line means on year. The Hopland replicate controls did not differ significantly from each other (HC1 - HC2 = .004 +/- .056 kg/yr), and the control line data were pooled (HC). The overall control line mean 120-d weights on a female, single, mature-dam basis were 33.2 and 30.4 kg at Davis and Hopland, respectively. Direct response was greater at Davis than at Hopland: DW - DC = .524 +/- .073 kg/yr (P less than .001); HW - HC = .151 +/- .034 kg/yr (P less than .001). Corresponding realized heritabilities were .17 and .06. Direct response for the DH line was DH - HC = .226 +/- .036 (P less than .001); realized heritability was .08. Response in the DH line was greater (P less than .05) than that in the HW line: HW - DH = -.075 +/- .037 kg/yr. This indicates that: (1) genetic improvement made on a higher plane of nutrition was expressed, but to a lesser degree, under range conditions and (2) selection under better feed conditions resulted in at least as much improvement in growth rate in a range environment as did selection under range conditions.


Anomalous magnetotransport properties of R2Mo2O7 near the magnetic phase boundary
The magnetic and transport properties of pyrochlore R2Mo2O7 have been studied with variation of the rare earth ( R). The change of the mean ionic radius of R, which induces change of the lattice structure, determines the magnetic ground state (ferromagnetic or spin glass), and the magnetic phase boundary is correlated with the metal-insulator crossover. Furthermore, we found enhanced magnetoresistance and unusual residual anomalous Hall effect at low temperatures near the phase boundary, which can be attributed to the coexistence of both phases.


Patterns of drug consumption and reported morbidity in Salamanca (Spain).
Health authorities need to have knowledge of the use of health services in order to be able to adopt suitable measures that will ensure a more rational use of pharmaceutical products. The information relative to drug consumption and expenditures can be obtained from different sources. In the present study a survey was carried out by interviewing Salamanca families in order to discover their degree of drug consumption and the expenses incurred therein. The drugs consumed by most families were analgesics-antiinflammatory agents and cardiovascular agents. Most families were found to spend less than 1000 pesetas per month. The expenses incurred were seen to depend on the family characteristics: age, educational status and income.


Erectile dysfunction in young patients is a proxy of overall men's health status.
This article summarizes current findings supporting the role of erectile dysfunction as a proxy of general health status, with a focus on the young population. Erectile dysfunction has been historically associated to increased cardiovascular risk and mortality. Several studies supported the role of erectile dysfunction as a predictive factor of subsequent cardiovascular events, acquiring significant importance even in young men. Similarly, erectile dysfunction emerged as a potential marker for metabolic alterations including diabetes mellitus and metabolic syndrome, eventually presenting as the initial manifestation of a dysmetabolic condition in young patients. Moreover, current epidemiologic data demonstrated a significant association of erectile dysfunction with several conditions including vascular, respiratory, gastrointestinal disorders, and endocrine with chronic-sustained inflammation representing the common pathophysiological link between erectile dysfunction and comorbidities. Interestingly, longitudinal studies demonstrated a higher risk of overall mortality in patients complaining of erectile dysfunction, even irrespective of cardiovascular risk. Erectile dysfunction does not represent an uncommon condition among young men. Considering the amount of data demonstrating a strong correlation between several life-risky comorbidities and erectile dysfunction, a careful and comprehensive general health assessment of patients complaining of erectile dysfunction should be carried out, regardless of patient's age. The identification of erectile dysfunction as an early sign of a major comorbidity would allow the implementation of therapeutic measures aimed at improving the overall health status and life expectancy across the entire aging process.


Effects of copper and zinc source on performance and humoral immune response of newly received, lightweight beef heifers.
Two experiments were conducted to evaluate the effects of Cu and Zn source on performance, morbidity, and humoral immune response in lightweight, newly received beef heifers. A 2 x 2 factorial arrangement of treatments was used in both experiments, with either a sulfate or a polysaccharide mineral complex (SQM) source of both Cu and Zn as the factors. Supplemental Cu and Zn were included in the receiving diet at concentrations designed to provide 10 mg of Cu/kg and 75 mg of Zn/kg (DM basis). In Exp. 1, 219 newly received beef heifers (British x Continental, average initial BW = 208 kg) were given ad libitum access to a 65% concentrate diet for 35 d to determine treatment effects on DMI, ADG, G:F, and bovine respiratory disease (BRD) morbidity. In Exp. 2, 24 heifers (average initial BW = 272 kg) were fed a diet with no supplemental Cu or Zn for 35 d, followed by fasting-refeeding-fasting stress, after which the same treatment diets used in Exp. 1 were fed for 21 d to examine the effects on humoral immune response (plasma IgG titer determined by ELISA on d 7, 14, and 21) to an ovalbumin (OVA) vaccine given on d 0 and 14. Copper source x Zn source interactions were not detected in either experiment. In Exp. 1, neither Cu nor Zn source affected (P > 0.10) DMI, ADG, G:F, or BRD morbidity. In Exp. 2, d 14 (P = 0.02) and 21 (P = 0.06) OVA titers were greater for heifers that received SQM Zn compared with heifers receiving ZnSO4, but heifers receiving CuSO4 had greater OVA titers than did heifers on the SQM Cu treatment on d 14 (P = 0.01) and 21 (P = 0.001). In summary, neither supplemental Cu nor Zn source affected performance or morbidity of lightweight, newly received heifers; however, source of both Cu or Zn affected the humoral immune response to OVA, although source effects were not consistent for the two minerals.


Creating a knowledge translation trainee collaborative: from conceptualization to lessons learned in the first year.
Trainees (e.g., graduate students, residents, fellows) are increasingly identifying knowledge translation as their research discipline. In Canada, a group of trainees have created a trainee-initiated and trainee-led national collaborative to provide a vehicle for trainees to examine the diversity of knowledge translation research and practice, and to link trainees from diverse geographical areas and disciplines. The aim of this paper is to describe our experience and lessons learned in creating the Knowledge Translation Trainee Collaborative. In this meeting report, we outline the process, challenges, and opportunities in planning and experiencing the collaborative's inaugural meeting as participant organizers, and present outcomes and learnings to date.


The Role of Extra-Articular Tenodesis in Combined ACL and Anterolateral Capsular Injury.
The "gold standard" treatment of anterolateral capsular injuries in anterior cruciate ligament (ACL)-deficient knees has not been determined. The purpose of this study was to determine the effects of ACL reconstruction and extra-articular reconstruction on joint motion in the ACL-deficient knee and in the combined ACL and anterolateral capsule-deficient knee. An anterior tibial load of 134 N and internal tibial torque of 7 Nm were applied to 7 fresh-frozen cadaveric knees using a robotic testing system continuously throughout the range of flexion. The resulting joint motion was recorded for 6 knee states: intact, ACL-deficient, ACL-reconstructed, combined ACL and anterolateral capsule-deficient, ACL-reconstructed + anterolateral capsule-deficient, and ACL-reconstructed + extra-articular tenodesis. Anterior tibial translation of the ACL-reconstructed + anterolateral capsule-deficient knee in response to an anterior tibial load was restored to that of the intact knee at all knee-flexion angles (p > 0.05). However, for this knee state, internal tibial rotation in response to internal tibial torque was not restored to that of the intact knee at 60° or 90° of knee flexion (p < 0.05). For the knee state of ACL-reconstructed + extra-articular tenodesis, internal rotation in response to internal tibial torque was restored to the motion of the intact knee at each of the tested knee-flexion angles (p > 0.05). Compared with the intact knee, 2 of 7 specimens showed decreased internal tibial rotation with ACL reconstruction + extra-articular tenodesis. In this study, an extra-articular tenodesis was necessary to restore rotatory knee stability in response to internal tibial torque in a combined ACL and anterolateral capsule-deficient knee. The amount of rotatory knee instability should be carefully assessed to avoid over-constraint of the knee in these combined ligament-reconstruction procedures. On the basis of our findings, the surgical procedure needs to be personalized depending on the amount of rotatory knee instability in the injured knee and the amount of rotation in the contralateral knee.


A new HPLC-ELSD method to quantify indican in Polygonum tinctorium L. and to evaluate beta-glucosidase hydrolysis of indican for indigo production.
A method to quantify the indigo precursor indican (indoxyl-beta-D-glucoside) in Polygonum tinctorium L. has been developed. Plant material was extracted in deionized water, and indican was identified and quantified using high performance liquid chromatography (HPLC) coupled to an evaporative light scattering detector (ELSD). Results confirmed that with this method it is possible to measure indican content in a short time, obtaining reliable and reproducible data. Using this method, leaf indican content was quantified every 15 days during the growing season (from May to October) in P. tinctorium crops grown in a field experiment in Central Italy. Results showed that indican increased along the growing season until flowering and was positively affected by photosynthetic active radiation (PAR). Indican is naturally hydrolyzed by native beta-glucosidase to indoxyl and glucose, the indoxyl yielding indigo. The activity of two enzymes, sweet almond beta-glucosidase and Novarom G preparation, were compared with P. tinctorium native beta-glucosidase to evaluate indigo production. Results showed that the ability to promote indigo formation increased as follows: almond beta-glucosidase <or= Novarom G.


Umbilical cord blood banking: public good or private benefit?
Haematopoietic stem cell transplantation (HSCT) is an accepted curative therapy for many malignant and non-malignant conditions affecting children and adults. Where possible, stem cells for HSCT are provided by human leukocyte antigen (HLA)-matched, related donors. Only 30% of patients have a suitable matched donor; for other patients, donors are sought from bone marrow registries or public umbilical cord blood (UCB) banks. While public UCB banks have been established to support transplant programs in Australia and internationally, parents also have the option of storing their child's UCB in a private commercial UCB bank for personal or family use. In contrast with public UCB banks, there is little social or medical justification for private UCB banking, as it provides no benefit to the community and little benefit to parents (other than reassurance and amelioration of regret), due to the very low likelihood of requiring autologous UCB later in life. Should UCB prove to be beneficial for tissue repair or replacement in the management of degenerative disorders, such as diabetes and Parkinson's disease, then a stronger case may be made in support of commercial banking of UCB for personal use. This may have a major impact on public UCB programs.


Jostra Rota Flow RF-30 pump system: a new centrifugal blood pump for cardiopulmonary bypass.
The Rota Flow pump is a fully integrated centrifugal pump system in the Jostra heart-lung machine HL-20 with features such as a less friction mono-pivot bearing system, sealless pump housing, and spiral housing. To evaluate its biocompatibility, antithrombogenesity, and hemolysis, we used it as a main pump of cardiopulmonary bypass (CPB) in coronary artery bypass grafting (CABG) cases and compared it with the BioMedicus pump. From February 1999 to May 1999, 30 consecutive patients underwent CABG under conventional CPB. Fifteen cases were supported by the Rota Flow RF-32 (Group R), and the remaining 15 were pumped by the BioMedicus BP-80 (Group B). In both groups, the flow rate was controlled in an equivalent value. Blood sampling was as follows: preoperative, 60 min after, postoperative Days (POD) 0, 1, and 2. We evaluated the plasma free hemoglobin (fHb) as the hemolysis parameter, beta-thromboglobulin (beta-TG) and platelet factor IV (PF-4) as the platelet deterioration index, C3, C4, and CH50 as complement activation, coagulation function, fibrinolytic factor and thrombomodulin, nitric oxide (NO), and endothelin as endothelial deterioration. This system was very easily and simply controlled and had excellent response. Perioperative laboratory data were not markedly changed in either group. The Rota Flow demonstrated equivalent value of biocompatibility and hemolysis as compared with the BioMedicus BP-80, which is a standard centrifugal pump. After pumping, no thrombus formation or pivot wear was observed inside the pump. This atraumatic, small centrifugal pump is suitable not only for CPB but also for long-term circulatory support.


Physical activity and sedentary behaviour: applying lessons to chronic obstructive pulmonary disease.
In health and disease, the benefits of regular participation in moderate to vigorous intensity physical activity are well documented. However, individuals with chronic conditions, such as those with chronic obstructive pulmonary disease (COPD), typically do very little activity at a moderate or vigorous intensity. Much of their day is instead spent in sedentary behaviour, such as sitting or reclining, which requires very little energy expenditure. This high level of time spent in sedentary behaviour can have serious health consequences, including increased risk of diabetes, cardiovascular disease and premature mortality. There is emerging evidence to suggest that participation in light intensity physical activities (e.g. standing or slow walking) may have benefits for cardio-metabolic health. Given the low aerobic capacity of individuals with moderate to severe COPD, increasing light intensity activity (through reducing sedentary time) may be a feasible additional strategy to improve health in this population, alongside traditional recommendations to increase the time spent in moderate to vigorous intensity physical activity. This review provides an overview of physical activity and sedentary behaviour, with a particular emphasis on these behaviours for people with COPD. It provides suggestions for the measurement of these behaviours within the clinical setting, as well as for interventions that may be effective at increasing physical activity and reducing sedentary behaviour in this population.


Together We Stand, Divided We Fall: A Multidisciplinary Approach in Complicated Acute Pancreatitis.
Acute pancreatitis (AP) is an inflammatory condition with a mild course in most patients, but 20-30% evolve to single or multiple organ dysfunction and pancreatic/peripancreatic necrosis, with potentially infected collections. In the first weeks of disease, a systemic inflammatory syndrome (SIRS) dominates the clinical setting, and early management decisions in this precocious phase can change the course of the disease. Imaging is crucial in the diagnosis, and since the adoption of the revised Atlanta classification, four different types of pancreatic/peripancreatic collections have been defined. The management of the complicated forms of AP has been defined by several treatment guidelines, and the main indication for intervention is local infection, preferably in walled-off necrosis. Open surgery necrosectomy is associated with a very high rate of morbimortality, giving a place to different multidisciplinary methodologies, emphasizing drainage and necrosectomy techniques in a "step-up" approach starting from mini-invasive endoscopic drainage and moving, if needed, to progressively more invasive techniques, including interventional radiology and mini-invasive surgery. With the advent of several new technologies in the specialties involved, the complicated AP cases which need drainage and necrosectomy benefit from a new era of multidisciplinary cooperation, permitting higher efficacy with lower levels of morbimortality and reducing hospital stay and costs.


Origin of Unusual Excitonic Absorption and Emission from Colloidal Ag2S Nanocrystals: Ultrafast Photophysics and Solar Cell.
Colloidal Ag2S nanocrystals (NCs) typically do not exhibit sharp excitonic absorption and emission. We first elucidate the reason behind this problem by preparing Ag2S NCs from nearly monodisperse CdS NCs employing cation exchange reaction. It was found that the defect-related midgap transitions overlap with excitonic transition, blurring the absorption spectrum. On the basis of this observation, we prepared nearly defect-free Ag2S NCs using molecular precursors. These defect-free Ag2S NCs exhibit sharp excitonic absorption, emission (quantum yield 20%) in near-infrared (853 nm) region, and improved performance of Ag2S quantum-dot-sensitized solar cells (QDSSCs). Samples with lower defects exhibit photoconversion efficiencies >1% and open circuit voltage of ∼0.3 V, which are better compared with prior reports of Ag2S QDSSCs. Femtosecond transient absorption shows pump-probe two-photon absorption above 630 nm and slow-decaying excited state absorption below 600 nm. Concomitantly, open-aperture z-scan shows strong two-photon absorption at 532 nm (coefficient 55 ± 3 cm/GW).


[Test of pituitary adrenal restraining with IV dexamethasone in the diagnosis of Cushing's syndrome (author's transl)].
The authors report a pituitary adrenal retraining test, using a 4 h IV infusion of dexamethasone phosphate (4 mg). Plasma cortisol is measured before and at the end of the infusion. The results allow a good discrimination between Cushing's disease (bilateral adrenal hyperplasia : 9 cases) and Cushing's syndrome of tumorous origin (adrenal tumors 7 cases, ectopic ACTH syndrome 3 cases, hypophyseal adrenomas 2 cases), only bilateral adrenal hyperplasia cases are lowering significantly.


The acute effect of a single dose of green tea on the quality and quantity of tears in normal eye subjects.
The study aimed to investigate the acute effect of a single dose of green tea on the quality and quantity of tears in normal eye subjects. Forty normal eye subjects (22 men and 18 women) aged 19-39 years were enrolled in the study. Also, an age matching control group (20 males and 20 females) was enrolled for comparison. McMonnies dry eye symptoms questionnaire and slit lamp were used for the exclusion criteria determination. Phenol red thread (PRT) test was performed on both eyes of each subject. A tear sample was collected from the lower tear meniscus of the right eye of each subject for the tear ferning (TF) test, which was performed before (30 minutes) and after (60 minutes) drinking green tea. The median PRT measurement after green tea consumption was lower (median [IQR]=23.50 [8.00] mm) compared to that before consumption (median [IQR]=27.00 [8.75] mm). In contrast, the median TF grade was significantly higher following green tea consumption than that before consumption (median [IQR]=2.65 [1.23] vs 1.50 [0.88] mm, respectively). The results show that TF grades increased in 97.5%, and the red phenol thread scores decreased in 80% of the subjects after green tea consumption compared to those before consumption. The PRT readings and TF grades were significantly different (P<0.05) before and after green tea consumption. Drinking green tea could have a significant effect on the eye tear film quality. Tear quality appeared to decrease after green tea consumption.


Chronic inactive pulmonary tuberculosis and treatment sequelae: chest radiographic features.
The chest radiograph (CXR) is a key initial tool in the diagnosis of many lung conditions, including pulmonary tuberculosis (TB). With proper use of anti-tuberculosis drugs, TB can be treated effectively and many CXR changes are limited. However, anti-tuberculosis drugs have not always been available, and in some cases they have not been started early in the disease process. The infection has then been able to take hold and cause significant radiologically visible damage, such as calcification and fibrosis. Before the use of anti-tuberculosis drugs, a variety of surgical techniques were employed to control pulmonary infection, including plombage, oleothorax, phrenic nerve crush and thoracoplasty. Each of these led to distinctive CXR features. This article sets out to describe the CXR features of chronic disease and surgical treatments, as their increasing rarity with the passage of time has meant that they can be misinterpreted. However, with increasing life expectancy and the revival of surgery due to the development of anti-tuberculosis drug resistance, the correct interpretation of these CXR changes is still of importance.


Molecular docking and ¬in-silico study of natural antagonists of ER-alpha receptor: Potential candidates against breast cancer.
Breast cancer is affecting the women in both developing and non-developing countries in a dangerous ratio. Estrogen receptor alpha (ER-α) controls a number of physiological processes. Its over expression is seen in breast cancer. Estrogen positive breast cancer can be treated by hormone therapy, that's why we focused on anti-estrogen natural molecules. A library of 5022 phytochemicals was searched, and selected top molecules based on their drug scoring. Fulvestrant was used as the reference drug. 4 molecules showed more drug scoring than the standard and these include Kushenol K, Flavobin, Kushenol N and CHEMBL66996 in descending order. All these molecules were further assessed for their other biological activities and found better than the standard. Therefore, these compounds may be used effectively as antagonists of ER-alpha receptor and as potential candidates against breast cancer.


Zebrafish genomic library in yeast artificial chromosomes.
We have constructed a zebrafish yeast artificial chromosome (YAC) library using genomic DNA isolated from the inbred AB zebrafish strain. The average insert size is 470 kb, estimated from analysis of 155 random selected YACs. The library consists of 17,000 clones, providing about a 4.7-fold coverage of zebrafish genome. The YAC clones have been arrayed in individual wells of 96-well microplates and also pooled to permit rapid polymerase chain reaction screening of the entire library. We have also found that the YAC ends can be easily rescued and sequenced from pRML1/pRML2-based mini-YAC clones.


Aberrant cerebral blood flow responses during cognition: Implications for the understanding of cognitive deficits in fibromyalgia.
There is ample evidence for cognitive deficits in fibromyalgia syndrome (FMS). The present study investigated cerebral blood flow responses during arithmetic processing in FMS patients and its relationship with performance. The influence of clinical factors on performance and blood flow responses were also analyzed. Forty-five FMS patients and 32 matched healthy controls completed a mental arithmetic task while cerebral blood flow velocities in the middle (MCA) and anterior (ACA) cerebral arteries were measured bilaterally using functional transcranial Doppler sonography (fTCD). Patients' cognitive processing speeds were slower versus healthy controls. In contrast to patients, healthy controls showed a pronounced early blood flow response (during seconds 4-6 after the warning signal) in all assessed arteries. MCA blood flow modulation during this period was correlated with task performance. This early blood flow response component was markedly less pronounced in FMS patients in both MCAs. Furthermore, patients displayed an aberrant pattern of lateralization, with right hemispheric dominance especially observed in the ACA. Severity of clinical pain in FMS patients was correlated with cognitive performance and cerebral blood flow responses. Cognitive impairment in FMS is associated with alterations in cerebral blood flow responses during cognitive processing. These results suggest a potential physiological pathway through which psychosocial and clinical factors may affect cognition.


Does 18F-FDG positron emission tomography-computed tomography have a role in initial staging of hepatocellular carcinoma?
The utility of fluorine-18 fluorodeoxyglucose ((18)F-FDG) positron emission tomography-computed tomography (PET/CT) in initial staging of hepatocellular carcinoma (HCC) has yet to be fully explored. We assessed the usefulness of (18)F-FDG PET/CT in initial staging of HCC. A total of 457 consecutive patients initially diagnosed with HCC at Seoul National University Hospital between 2006 and 2012 were evaluated retrospectively to assess the impact of (18)F-FDG PET/CT on staging and compliancy with Milan criteria, relative to dynamic CT of liver and chest x-ray. Seven among the 457 patients studied showed a shift in Barcelona Clinic Liver Cancer [BCLC] stage (A → C: 6 patients; B → C: 1 patient) and 5 patients who had originally met Milan criteria no longer qualified. (18)F-FDG PET/CT had value in initial staging of early (stage A) or intermediate (stage B) HCC, as determined by dynamic CT of liver and BCLC or AJCC classifications, whereas BCLC stage 0 and stage C tumors were unchanged (P<0.001). (18)F-FDG PET/CT disclosed additional metastases in patients with American Joint Committee on Cancer [AJCC] T2 (2.7%), T3a (5.3%), and T3b (4.8%) classifications. In initial staging of HCC, (18)F-FDG PET/CT provided additional information, impacting the patients with BCLC (stages A and B) and AJCC (T2 and T3) classifications. Its use might be thus appropriate for these patient subsets, especially if hepatic resection or liver transplantation is planned.


Poliovirus morphogenesis. I. Identification of 80S dissociable particles and evidence for the artifactual production of procapsids.
The current model of poliovirus morphogenesis postulates a fundamental role for procapsid, 80S shells that, upon interaction with viral RNA and subsequent proteolytic cleavage, give rise to complete virus particles. Although 80S sedimenting particles can, indeed, be isolated from cytoplasmic extracts of infected cells, their physical properties differ from those reported for procapsids. Far from being stable structures, they can be dissociated by pH 8.5 and 0.1% sodium dodecyl sulfate into slower-sedimenting subunits. The reasons for this discrepancy were investigated, and two main modalities leading to the appearance of procapsids in vitro were identified. The first involves a temperature-mediated conversion of dissociable 80S particles into stable 80S procapsids, and the second involves the self-assembly of endogenous 14S subunits, also primed by an increase in the temperature of cytoplasmic extracts.


Eukaryotic DNA polymerase amino acid sequence required for 3'----5' exonuclease activity.
We have identified an amino-proximal sequence motif, Phe-Asp-Ile-Glu-Thr, in Saccharomyces cerevisiae DNA polymerase II that is almost identical to a sequence comprising part of the 3'----5' exonuclease active site of Escherichia coli DNA polymerase I. Similar motifs were identified by amino acid sequence alignment in related, aphidicolin-sensitive DNA polymerases possessing 3'----5' proofreading exonuclease activity. Substitution of Ala for the Asp and Glu residues in the motif reduced the exonuclease activity of partially purified DNA polymerase II at least 100-fold while preserving the polymerase activity. Yeast strains expressing the exonuclease-deficient DNA polymerase II had on average about a 22-fold increase in spontaneous mutation rate, consistent with a presumed proofreading role in vivo. In multiple amino acid sequence alignments of this and two other conserved motifs described previously, five residues of the 3'----5' exonuclease active site of E. coli DNA polymerase I appeared to be invariant in aphidicolin-sensitive DNA polymerases known to possess 3'----5' proofreading exonuclease activity. None of these residues, however, appeared to be identifiable in the catalytic subunits of human, yeast, or Drosophila alpha DNA polymerases.


Muscle-specific expression of insulin-like growth factor I counters muscle decline in mdx mice.
Duchenne muscular dystrophy is an X-linked degenerative disorder of muscle caused by the absence of the protein dystrophin. A major consequence of muscular dystrophy is that the normal regenerative capacity of skeletal muscle cannot compensate for increased susceptibility to damage, leading to repetitive cycles of degeneration-regeneration and ultimately resulting in the replacement of muscle fibers with fibrotic tissue. Because insulin-like growth factor I (IGF-I) has been shown to enhance muscle regeneration and protein synthetic pathways, we asked whether high levels of muscle-specific expression of IGF-I in mdx muscle could preserve muscle function in the diseased state. In transgenic mdx mice expressing mIgf-I (mdx:mIgf+/+), we showed that muscle mass increased by at least 40% leading to similar increases in force generation in extensor digitorum longus muscles compared with those from mdx mice. Diaphragms of transgenic mdx:mIgf+/+ exhibited significant hypertrophy and hyperplasia at all ages observed. Furthermore, the IGF-I expression significantly reduced the amount of fibrosis normally observed in diaphragms from aged mdx mice. Decreased myonecrosis was also observed in diaphragms and quadriceps from mdx:mIgf+/+ mice when compared with age-matched mdx animals. Finally, signaling pathways associated with muscle regeneration and protection against apoptosis were significantly elevated. These results suggest that a combination of promoting muscle regenerative capacity and preventing muscle necrosis could be an effective treatment for the secondary symptoms caused by the primary loss of dystrophin.


New far UV detector calibration facility at the National Bureau of Standards.
A description is given of a new facility, located at the NBS (Gaithersburg) Synchrotron Ultraviolet Radiation Facility (SURF-II), in which the absolute calibration of working standard detectors for the 5-50-nm spectral region, and the subsequent calibration of outgoing transfer standard detectors is performed. A dual toroidal grating monochromator, with diffraction gratings optimized for 3-13 and 12-52 nm, disperses synchrotron radiation from the electron storage ring into tandem experimental chambers in which a rare gas ionization chamber determines the absolute magnitude of the incident radiant flux and hence the efficiency of the photoemissive photodiodes.


[Changes in calcium-dependent potassium channels of isolated smooth muscle cells of the bladder in rats with experimental diabetes].
Activation of large conductance Ca2+-dependent potassium channels (BK channels) influences repolarization of the action potential and the level of the resting potential of detrusor smooth muscle cells (SMC). Overactive bladder syndrome (OBS) is one of the complications of diabetes. Here using whole-cell patch clamp technique we show sizable reduction of depolarization-evoked BK current (lBK) and decrease in the amplitude and frequency of spontaneous transient outward currents (STOCs) in isolated SMC from detrusor of rats with streptozocin-induced diabetes compared to control animals. Under the diabetes IBK density at step depolarization to +50 mV decreased from control value of 15.0+/-0.4 pA/pF to 10.0+/-0.5 pA/pF, whereas the mean values of the STOCs' frequency and amplitude at holding potential -20 mV were reduced from 12.0+/-1.5 Hz to 2.4+/-0.6 Hz and from 0.9+/-0.1 pA/pF to 0.510.1 pA/pF, respectively. Using real time RT-PCR it was found that the expression of mRNA for the BK-channel primary pore-forming KCa1.1-subunit increases under the diabetes, whilst that for the auxiliary BKCabeta1-subunit decreases. It is concluded that the observed changes in the BK-channel currents can enhance excitability of the detrusor SMCs thereby promoting myogenic OBS. However, further studies are needed to determine how the decrease in BKCabeta1 expression under the diabetes impairs functional properties of BK channels and to establish possible changes in calcium signals that modulate channel activation.


Short-term adaptation of postprandial lipoprotein secretion and intestinal gene expression to a high-fat diet.
Western diet is characterized by a hypercaloric and hyperlipidic intake, enriched in saturated fats, that is associated with the increased occurrence of metabolic diseases. To cope with this overload of dietary lipids, the intestine, which delivers dietary lipids to the body, has to adapt its capacity in lipid absorption and lipoprotein synthesis. We have studied the early effects of a high-fat diet (HFD) on intestinal lipid metabolism in mice. After 7 days of HFD, mice displayed normal fasting triglyceridemia but postprandial hypertriglyceridemia. HFD induced a decreased number of secreted chylomicrons with increased associated triglycerides. Secretion of larger chylomicrons was correlated with increased intestinal microsomal triglyceride transfer protein (MTP) content and activity. Seven days of HFD induced a repression of genes involved in fatty acid synthesis (FAS, ACC) and an increased expression of genes involved in lipoprotein assembly (apoB, MTP, and apoA-IV), suggesting a coordinated control of intestinal lipid metabolism to manage a high-fat loading. Of note, the mature form of the transcription factor SREBP-1c was increased and translocated to the nucleus, suggesting that it could be involved in the coordinated control of gene transcription. Activation of SREBP-1c was partly independent of LXR. Moreover, HFD induced hepatic insulin resistance whereas intestine remained insulin sensitive. Altogether, these results demonstrate that a short-term HFD is sufficient to impact intestinal lipid metabolism, which might participate in the development of dyslipidemia and metabolic diseases.


Living evidence of a fossil survival strategy raises hope for warming-affected corals.
Climate change is affecting reef-building corals worldwide, with little hope for recovery. However, coral fossils hint at the existence of environmental stress-triggered survival strategies unreported in extant colonial corals. We document the living evidence and long-term ecological role of such a survival strategy in which isolated polyps from coral colonies affected by warming adopt a transitory resistance phase, in turn expressing a high recovery capacity in dead colony areas. Such processes have been described in fossil corals as rejuvenescence but were previously unknown in extant reef-builder corals. Our results based on 16 years of monitoring show the significance of this process for unexpected recoveries of coral colonies severely affected by warming. These findings provide a link between rejuvenescence in fossil and extant corals and reveal that beyond adaptation and acclimatization processes, modern scleractinian corals show yet undiscovered and highly effective survival strategies that help them withstand and recover from rapid environmental changes.


[Effect of prostaglandin E2, dexamethasone, and exertion on adrenocortical and sympathetic adrenal activity in dogs].
Influence of dexamethasone, prostaglandin E2 (PGE2) and physical load on activity of corticotropin, 11-oxycorticosteroids (11-OHCS), adrenaline, noradrenaline, glucose in arterial blood was studied in chronic experiment on dogs. A comparison with intact dog responses to exogenous PGE2 revealed an increase of corticotropin and 11-OHCS and a decrease of noradrenaline in arterial blood. Dexamethasone prevented adrenocortical activity in response to PGE2; it helped, however, to increase activity of noradrenaline.


Depression in Alzheimer's disease: epidemiology, mechanisms, and management.
Depression occurs with a high prevalence of up to 50% in patients with Alzheimer's disease (AD) and increases the caregivers' burden. Depression symptoms can precede clinical diagnosis of AD for years or occurs around the onset of AD, although the etiology and pathologic mechanism of depression in AD pathogenesis remain unclear. Here, we provide an overview on recent studies, indicating that genetic factors, neuroanatomic changes, vascular risk factors, and the imbalance of neurotransmitters might contribute to depressive symptoms in AD. Tau pathology and amyloid-β accumulation also correlate with depression in AD. In addition, the alteration of hypothalamic-pituitary-adrenal axis, inflammatory pathway, and neurotrophin deficiency are the possible biological mechanisms linking depression and AD, and might become the potential targets for AD treatment. Current data support that antidepressants are promising to alleviate the symptom, though the efficacy is controversial. Moreover, antidementia medication and non-pharmacological interventions can be potential choices. In this review, we describe the prevalence and clinical course of depression in AD, analyze the underlying mechanisms, and discuss the possible management strategies for depression in patients with AD.


A circularly focused and scanned acoustic scanner.
This paper describes a new type of electronically scanned and focused acoustic imaging device called the cylindrical grating acoustic scanner. With this device, a new transducer called the circular-edge-bonded transducer (CEBT) is devised that is bonded on one end of a cylindrical substrate and can generate a surface acoustic wave propagating along the cylindrical surface of the substrate. An array of grooves is fabricated on the cylindrical surface of the substrate to serve as a scattering grating. The periodical grooves scatter a chirped surface-wave pulse coherently into a focused bulk-wave "ring" that scans at the surface-wave velocity. The focal length and resolution can be adjusted by changing the chirp rate and time-bandwidth product of the chirp, respectively. A 2.3-MHz circular scanner with 25-cm field of view and 2.6-mm resolution has been constructed and studied. Acoustic image of an artificial defect in an aluminum pipe is obtained.


Multijoint movement control: the importance of interactive torques.
The underlying mechanisms of the neural control of movement have long been explored, with a focus primarily on central control aspects and often overlooking the intrinsic mechanical properties of the motor system. To fully understand the control and regulation of movements, the biomechanical properties of the moving subject, specifically interactive torques, must be considered in the design, evaluation, and interpretation of empirical data. We first discuss the difficulty of extrapolating information from a wide variety of tasks due to their varying inherent task constraints. Examples are subsequently given where a biomechanical perspective provides a more informative interpretation of existing data. Finally, we focus on research examining the role of interactive torques with a discussion of how discoordinated movements may be explained by an inability to modulate interactive torques. Inclusion of biomechanical considerations in motor control research is a step toward incorporating multilevel methodologies and interpretations into the field, and providing a more comprehensive understanding of the neural control and regulation of movement.


Effects of inhibition of thromboxane A2 synthesis in aspirin-induced asthma.
Since inhibition of cyclooxygenase precipitates asthmatic attacks in patients with aspirin idiosyncrasy, we have evaluated the effects of pharmacologic inhibition of thromboxane A2 (TXA2) synthetase, next to cyclooxygenase enzyme in arachidonic acid cascade. Sixteen patients with aspirin-induced asthma received increasing doses on 3 days (25 to 400 mg) of an imidazole derivative, OKY-046, which specifically blocks TXA2 synthetase. Twenty-three healthy control subjects received a single dose of 400 mg of OKY-046. In both patients and control subjects, the inhibitor at a dose of 400 mg produced (1) a pronounced fall in thromboxane B2 serum levels, (2) a rise in serum 6-keto-prostaglandin F1 alpha, and (3) a depression in platelet aggregability to arachidonic acid and adenosine diphosphate. The drug, however, neither precipitated attacks of asthma nor impaired pulmonary function tests throughout a 24-hour observation period. Five patients, but none of the control subjects, developed transient nasal congestion about 1 hour after taking the drug. Thus, inhibition of TXA2 synthetase, contrary to inhibition of cyclooxygenase, does not affect bronchopulmonary function in patients with asthma and aspirin intolerance.


Temporal intraspecific trait variability drives responses of functional diversity to interannual aridity variation in grasslands.
Interannual climate variation alters functional diversity through intraspecific trait variability and species turnover. We examined these diversity elements in three types of grasslands in northern China, including two temperate steppes and an alpine meadow. We evaluated the differences in community-weighted means (CWM) of plant traits and functional dispersion (FDis) between 2 years with contrasting aridity in the growing season. Four traits were measured: specific leaf area (SLA), leaf dry matter content (LDMC), leaf nitrogen concentration (LNC), and the maximum plant height (H). CWM for SLA of the alpine meadow increased in the dry year while that of the temperate steppe in Qinghai showed opposing trends. CWM of LDMC in two temperate steppes became higher and CWM of LNC in all grasslands became lower in the dry year. Compared with the wet year, FDis of LDMC in the alpine meadow and FDis of LNC in the temperate steppe in Qinghai decreased in the dry year. FDis of H was higher in the dry year for two temperate steppes. Only in the temperate steppe in Qinghai did the multi-FDis of all traits experience a significant increase in the dry year. Most of the changes in CWM and FDis between 2 years were explained by intraspecific trait variation rather than shifts in species composition. This study highlights that temporal intraspecific trait variation contributes to functional responses to environmental changes. Our results also suggest it would be necessary to consider habitat types when modeling ecosystem responses to climate changes, as different grasslands showed different response patterns.


"The obesity paradox" in disease--is the protective effect of obesity true?
Although obesity and the associated metabolic syndrome negatively impact on health outcomes, a paradoxical relationship between obesity and mortality has been reported for specific patient populations - the "obesity paradox". However, underlying mechanisms remain unclear and several possible explanations are being discussed. First, a true protective effect of obesity is possible, mediated through differences in the immune response and more metabolic reserves. Although there is a growing body of evidence supporting this hypothesis, the influence of obesity on immune function is complex and not completely understood. Second, a statistical bias is possible, owing to confounding, selection bias, performance bias and measurement bias of most observational studies reporting the obesity paradox. Within this article, we summarise current concepts regarding the underlying pathophysiology and possible explanation for the obesity paradox, and discuss open questions such as whether age is an effect modifier on the relationship of obesity and mortality.


Redberry juniper as a roughage source in lamb feedlot rations: performance and serum nonesterified fatty acids, urea nitrogen, and insulin-like growth factor-1 concentrations.
Effects of replacing cottonseed hulls with dry redberry juniper leaves on performance and serum NEFA, urea N, and IGF-1 were investigated in Rambouillet lambs (n = 24, initial BW = 28.6 +/- 4.94 kg). In a study with 2 feeding periods (period 1 = 65% concentrate ration, 28 d; period 2 = 85% concentrate ration, 49 d), lambs were individually fed ad libitum treatment diets containing cottonseed hulls (control; CSH), one-half of the cottonseed hulls replaced by dry juniper leaves (CSHJ), or all the cottonseed hulls replaced by dry juniper leaves (JUN). Lamb BW was similar on d 0 and 14, but increasing juniper in the diet linearly reduced (P = 0.04) BW on d 28. Differences in BW during period 1 are attributed to ADG and average daily DMI linearly decreasing (P < 0.001) with increasing concentrations of juniper, with lambs fed CSH, CSHJ, or JUN diets having ADG of 0.34, 0.30, and 0.14 kg, respectively. Differences in average daily DMI are attributed to secondary compounds in the cottonseed hulls and juniper and nutrient-toxin interactions. Lambs fed CSHJ diets had the greatest (P = 0.04) G:F compared with lambs fed CSH and JUN during period 1. Lambs fed JUN diets tended to have the greatest (P = 0.09) NEFA concentrations during period 1, and increasing juniper in the diet linearly reduced (P = 0.006) serum urea N and IGF-1 on d 14 and 28, respectively. During period 2, intake and growth of lambs fed JUN diet rapidly increased, resulting in all lambs having similar ADG, DMI, G:F, and BW. When period 2 began (d 33), serum NEFA and urea N were similar (P > 0.12) among lambs, but serum IGF-1 tended to be linearly reduced (P = 0.09) by increasing juniper in the diet. At times during period 2, lambs fed CSHJ had the greatest (P < 0.02) serum urea N (d 40 and 82) and IGF-1 (d 54) concentrations. Results were interpreted to indicate that air-dried redberry juniper leaves can replace all of the cottonseed hulls in lamb feedlot rations. Feeding 30% juniper in the diet for a longer period of time during the initial feeding period probably would have further reduced growth performance.


High Oxide-Ion Conductivity in a Hexagonal Perovskite-Related Oxide Ba7 Ta3.7 Mo1.3 O20.15 with Cation Site Preference and Interstitial Oxide Ions.
Solid oxide-ion conductors are crucial for enabling clean and efficient energy devices such as solid oxide fuel cells. Hexagonal perovskite-related oxides have been placed at the forefront of high-performance oxide-ion conductors, with Ba7 Nb4- x Mo1+ x O20+ x /2 (x = 0-0.1) being an archetypal example. Herein, high oxide-ion conductivity and stability under reducing conditions in Ba7 Ta3.7 Mo1.3 O20.15 are reported by investigating the solid solutions Ba7 Ta4- x Mo1+ x O20+ x /2 (x = 0.2-0.7). Neutron diffraction indicates a large number of interstitial oxide ions in Ba7 Ta3.7 Mo1.3 O20.15 , leading to a high level of oxide-ion conductivity (e.g., 1.08 × 10-3 S cm-1 at 377 °C). The conductivity of Ba7 Ta3.7 Mo1.3 O20.15 is higher than that of Ba7 Nb4 MoO20 and conventional yttria-stabilized zirconia. In contrast to Ba7 Nb4- x Mo1+ x O20+ x /2 (x = 0-0.1), the oxide-ion conduction in Ba7 Ta3.7 Mo1.3 O20.15 is dominant even in highly reducing atmospheres (e.g., oxygen partial pressure of 1.6 × 10-24 atm at 909 °C). From structural analyses of the synchrotron X-ray diffraction data for Ba7 Ta3.7 Mo1.3 O20.15 , contrasting X-ray scattering powers of Ta5+ and Mo6+ allow identification of the preferential occupation of Mo6+ adjacent to the intrinsically oxygen-deficient layers, as supported by DFT calculations. The high conductivity and chemical and electrical stability in Ba7 Ta3.7 Mo1.3 O20.15 provide a strategy for the development of solid electrolytes based on hexagonal perovskite-related oxides.


Insulin degludec in the first trimester of pregnancy: Report of two cases.
Insulin degludec is an extra-long-acting insulin analog that allows for enhanced efficacy and flexibility in the injection time. However, it is not approved for use during pregnancy. We report the pregnancy outcome and newborn conditions in two women with type 1 diabetes who continued preconception degludec treatment during embryogenesis. No pregnancy complication or congenital neonatal malformation was observed. Both babies presented with hypoglycemia and required neonatal intensive care unit admission. Degludec treatment did not cause adverse effects in the mothers or malformations in the newborns. The observed neonatal complications were probably independent of early pregnancy degludec treatment.


The afferent input to the magnocellular division of the mediodorsal thalamic nucleus in the monkey, Macaca fascicularis.
The origin and termination of fibers to the mediodorsal thalamic nucleus, especially those to the medial, magnocellular part of the nucleus (MDm), have been studied using anterograde and retrograde axonal tracing methods, as well as electrophysiological recording. The results indicate that in addition to its well-known connections to and from the prefrontal cortex, MDm receives fibers from many parts of the basal forebrain, including the ventral pallidum and other parts of the substantia innominata, the amygdaloid complex, the primary olfactory cortex, entorhinal and perirhinal cortex, and the cortex at the pole of the temporal lobe. Lighter projections arise in the subiculum, the ventral insula, and the superior and inferior temporal gyri. The cells that project to MDm tend to be large, polymorphic neurons. Throughout most of the basal forebrain they are diffusely distributed through several nuclei or cortical layers, without obvious relation to nuclear or laminar boundaries. The major exception to this is in the ventral pallidum, where there is a dense concentration of cells that project to MDm. The lateral part of the mediodorsal nucleus (MDl) receives few if any fibers from the basal forebrain and temporal lobe, but is innervated by several brainstem structures, especially the superior colliculus, the substantia nigra, the medial vestibular nucleus, and the midbrain tegmental fields. In MDm, the fibers are distributed in irregular patches. Three-dimensional analysis indicates that these patches are often clustered into separate bands or columns at different anteroposterior levels. In addition, the strongest projections from the three major regions that innervate MDm are organized in a complex three-dimensional pattern. First, the fibers from the amygdaloid nuclei terminate most heavily (but not exclusively) in the rostral third of MDm. The parvicellular accessory basal amygdaloid nucleus and the amygdalohippocampal area project principally to the dorsal part of the nucleus. The parvicellular basal nucleus and the periamygdaloid cortex project to the ventromedial quadrant of MDm; and the magnocellular basal nucleus, the magnocellular accessory basal nucleus, and the lateral nucleus all project to the ventrolateral quadrant. Second, the substantia innominata projects preferentially to the caudal part of MDm. The medial part of the substantia innominata, especially the ventral pallidum, innervates the dorsomedial quadrant, while more caudal and lateral areas of this region project ventrolaterally. Third, the projections arising from the entorhinal and other temporal cortical areas terminate primarily in the mid-rostrocaudal level of MDm.(ABSTRACT TRUNCATED AT 400 WORDS)


Preliminary molecular genetic analysis of the Receptor Interacting Protein 140 (RIP140) in women affected by endometriosis.
Endometriosis is a complex disease affecting 10-15% of women at reproductive age. Very few genes are known to be altered in this pathology. RIP140 protein is an important cofactor of oestrogen receptor and many other nuclear receptors. Targeting disruption experiments of nrip1 gene in mice have demonstrated that nuclear receptor interacting protein 1 gene (nrip1), the gene encoding for rip140 protein, is essential for female fertility. Specifically, mice null for nrip1 gene are viable, but females are infertile because of complete failure of mature follicles to release oocytes at ovulation stage. The ovarian phenotype observed in mice devoid of rip140 closely resembles the luteinized unruptured follicle (LUF) syndrome that is observed in a high proportion of women affected of endometriosis or idiopathic infertility. Here we present a preliminary work that analyses the role of NRIP1 gene in humans. We have sequenced the complete coding region of NRIP1 gene in 20 unrelated patients affected by endometriosis. We have performed genetic association studies by using the DNA variants identified during the sequencing process. We identified six DNA variants within the coding sequence of NRIP1 gene, and five of them generated amino acid changes in the protein. We observed that three of twenty sequenced patients have specific combinations of amino-acid variants within the RIP140 protein that are poorly represented in the control population (p = 0.006). Moreover, we found that Arg448Gly, a common polymorphism located within NRIP1 gene, is associated with endometriosis in a case-control study (59 cases and 141 controls, Pallele positivity test = 0.027). Our results suggest that NRIP1 gene variants, separately or in combinations, might act as predisposing factors for human endometriosis.


Inversion of the 11Bu and 21Ag electronic states of all-trans-1,6-diphenyl-1,3,5-hexatriene in carbon disulfide.
From the analysis of UV/Vis absorption spectra, emission and excitation emission spectra of solutions of all-trans-1,6-diphenyl-1,3,5-hexatriene (DPH) in carbon disulfide (CS2) within a wide range of temperatures, we can conclude that these spectra do not support the inversion of excited electronic states in DPH by an increased polarizability of the solvent as proposed by Kohler and Itoh. The proposal by Kohler and Itoh is widely accepted as an elegant demonstration of the inversion of the 11Bu and 21Ag states in the polyene DPH by a mere increase in the solvent polarizability. The evidence provided in this paper confirms, as has recently been proposed, that a ghost state as the first electronic state, 21Ag, is not necessary to explain the photophysics of DPH. The photophysics of DPH is plausibly explicable with the 11Bu state, which is directly excitable by photonic absorption from the fundamental electronic state of the compound. In this paper, we provide evidence that the UV/Vis spectra of DPH in CS2 at 77 K are most likely generated from a molecular structure of DPH constrained by solid CS2, which is clearly distinct from that present in liquid CS2.


Mobility, mortality, and the middle ages: identification of migrant individuals in a 14th century black death cemetery population.
Mobility and migration patterns of groups and individuals have long been a topic of interest to archaeologists, used for broad explanatory models of cultural change as well as illustrations of historical particularism. The 14th century AD was a tumultuous period of history in Britain, with severely erratic weather patterns, the Great Famine of 1315-1322, the Scottish Wars of Independence, and the Hundred Years' War providing additional migration pressures to the ordinary economic issues drawing individuals to their capital under more stable conditions. East Smithfield Black Death Cemetery (Royal Mint) had a documented use period of only 2 years (AD 1348-1350), providing a precise historical context (∼50 years) for data. Adults (n = 30) from the East Smithfield site were sampled for strontium and oxygen stable isotope analyses of tooth enamel. Five individuals were demonstrated to be statistical outliers through the combined strontium and oxygen isotope data. Potential origins for migrants ranged from London's surrounding hinterlands to distant portions of northern and western Britain. Historic food sourcing practices for London were found to be an important factor for consideration in a broader than expected (87) Sr/(86) Sr range reflected in a comparison of enamel samples from three London datasets. The pooled dataset demonstrated a high level of consistency between site data, divergent from the geologically predicted range. We argue that this supports the premise that isotope data in human populations must be approached as a complex interaction between behavior and environment and thus should be interpreted cautiously with the aid of alternate lines of evidence.


On the nature of the stimulation of the lipoxygenase from rabbit reticulocytes by biological membranes.
The oxygenation of concentrated emulsions (about 260 microM) of arachidonic acid or linoleic acid catalyzed by the purified lipoxygenase from rabbit reticulocytes is strongly stimulated in the presence of low concentrations of beef heart submitochondrial particles or other membrane preparations. Maximal stimulation was observed at a proportion of about 5 mumoles polyenoic acid per mg of membrane protein. Whereas at a constant ratio of arachidonic acid and membranes the reaction rate obeyed the Michaelis-Menten kinetics with an apparent Km value of 75 microM for arachidonic acid, sigmoid kinetics was observed under conditions of constant concentration of membranes and, consequently, varying proportions of arachidonate and membranes. Under conditions of maximal stimulation binding of reticulocyte lipoxygenase to the membranes was insignificant. Moreover, one-third of the arachidonic acid sedimented during ultracentrifugation of the membranes as judged from experiments with [14C] arachidonic acid. From other sedimentation experiments and from the comparison with soybean lipoxygenase which is not stimulated by membranes it is concluded that the emulsion droplets interacting with the membranes are the substrate of the stimulated reaction. The stimulation may be brought about by facilitating the susceptibility of the fatty acids to reticulocyte lipoxygenase. The membrane-stimulated reaction of reticulocyte lipoxygenase was not inhibited by the antioxidant 2,6-di-t-butyl-4-hydroxytoluene (BHT) excluding the participation of free radicals. The stimulatory effect of membranes seems not to be related to their susceptibility towards lipoxygenase attack which varied strongly in order mitochondrialmembranes greater than endoplasmic membranes greater than erythrocyte ghosts. The stimulation by membranes resembles that produced by the detergent sodium cholate at concentrations near to the critical micellar concentration. Moreover, the stimulations by membranes and by cholate do not behave synergistically or abolish each other. The stimulatory effect of membranes did not occur at a proportion of 200 nmoles per mg of membrane protein.


Fungicidal activity of lysozyme is inhibited in vitro by commercial sinus irrigation solutions.
Lysozyme is an innate immune peptide with bactericidal and fungicidal activity (FA). Despite increased expression of lysozyme protein in chronic rhinosinusitis (CRS) sinus mucosa, CRS patients experience repeated bacterial and/or fungal infections. Commercial sinus irrigation solutions are often used to provide symptomatic relief. However, one of the mechanisms of action of lysozyme involves ionic interactions with the microbial cell wall, which may be inhibited by ionic solutions such as commercial sinus irrigation solutions. Determine if the FA of lysozyme is reduced in the presence of solutions with increasing ionic strength and inhibited in the presence of commercial sinus irrigation solutions. Using an in vitro colony-forming unit (CFU) assay, the FA of lysozyme (5 μM) was tested against a fungi commonly isolated from CRS patients, Aspergillus fumigatus, in solutions of increasing ionic strength or commercial sinus irrigation solutions. FA was presented as percent of control. FA of lysozyme against A. fumigatus was 95% in a 21-mM ionic strength solution. However, with increasing ionic strength, FA decreased and was abolished in a 46-mM ionic strength solution. Commercial sinus irrigation solutions abolished the FA of lysozyme against A. fumigatus. The in vitro FA of lysozyme is dependent on the ionic strength of the solution. The use of sinus irrigation solutions should be further evaluated with regard to maintaining functional activity of cationic antimicrobial peptides involved in sinonasal innate immunity.


Quality, risk management and governance in mental health: an overview.
To consider the origin, current emphasis and relevance of the concepts of quality, risk management and clinical governance in mental health. Increasingly, health service boards and management teams are required to give attention to clinical governance rather than corporate governance alone. Clinical governance is a unifying quality concept that aims to produce a structure and systems to assure and improve the quality of clinical services by promoting an integrated and organization-wide approach towards continuous quality improvement. Many psychiatrists will find the reduction in clinical autonomy, the need to consider the welfare of the whole population as well as the individual patient for whom they are responsible, and the requirement that they play a part in a complex systems approach to quality improvement to be a challenge. Avoiding or ignoring this challenge will potentially lead to conflict with modern management approaches and increased loss of influence on future developments in mental health services.


Utilisation of malaria preventive measures during pregnancy and birth outcomes in Ibadan, Nigeria.
Malaria remains a major public health problem in sub Saharan Africa and the extent of utilisation of malaria preventive measures may impact on the burden of malaria in pregnancy. This study sought to determine the association between malaria preventive measures utilized during pregnancy and the birth outcomes of birth weight and preterm delivery. This cross sectional survey involved 800 mothers who delivered at the University College Hospital, and Adeoyo Maternity Hospital, Ibadan. Data obtained included obstetric information, gestational age, birth weight and self reported use of malaria prevention strategies in index pregnancy. Most (95.6%) mothers used one or more malaria control measures. The most commonly used vector control measures were window net (84.0%), insecticide spray (71.5%) and insecticide treated bed nets (20.1%), while chemoprophylactic agents were pyrimethamine (23.5%), Intermittent Preventive Treatments with Sulphadoxine-Pyrimethamine (IPTsp) (18.5%) and intermittent chloroquine (9.5%) and 21.7% used herbal medications. The mean ± SD birthweight and gestational age of the babies were 3.02 kg ± 0.56 and 37.9 weeks ± 2.5 respectively. Preterm delivery rate was 19.4% and 9% had low birth weight. Comparing babies whose mothers had IPTsp with those who did not, mean birth weight was 3.13 kg ± 0.52 versus 3.0 kg ± 0.56 (p = 0.016) and mean gestational age was 38.5 weeks ± 2.1 versus 37.8 weeks ± 2.5 (p = 0.002). The non-use of IPTsp was associated with increased risk of having low birth weight babies (AOR: 2.27, 95% CI: 0.98; 5.28) and preterm birth (AOR: 1.93, 95% CI: 1.08, 3.44). The non use of herbal preparations (AOR: 0.55, 95% CI: 0.36, 0.85) was associated with reduced risk of preterm birth. The mean ± SD birth weight and gestational ages of babies born to mothers who slept under ITNs were not significantly different from those who did not (p = 0.07 and 0.09 respectively). There is a need for improved utilisation of IPTsp as well as discouraging the use of herbal medications in pregnancy in order to reduce pregnancy outcome measures of low birth weight and preterm deliveries in this environment.


Identification of 14 kDa auxin-binding proteins in a tobacco plasma membrane subfraction responsive to auxin.
Auxin binding by tobacco plasma membrane proteins was investigated. After photolabeling with [3H]IAA, 350 polypeptides were resolved on 2D gels and analyzed. Thirteen polypeptides were selected according to physico-chemical criteria. The labeling of three of them was further shown to increase, after treatment of cells with auxin, specifically in that plasma membrane subfraction where the sensitivity to the hormone of the H(+)-ATPase is enhanced by the treatment of cells. These polypeptides were those that exhibited the more specific labeling features according to physico-chemical criteria. They had similar apparent molecular weight (ca 14 kDa) that distinguished them from other auxin-binding proteins described up to now, and exhibited similar amino acid compositions. These 14 kDa polypeptides are proposed to constitute a group of new auxin-binding proteins, potentially involved, within specialized plasma membrane domains, in the stimulation of the proton pump by the hormone.


Conjugated polyelectrolytes with guanidinium side groups. Synthesis, photophysics and pyrophosphate sensing.
Two cationic poly(phenylene ethynylene) conjugated polyelectrolytes (CPEs) featuring guanidinium side groups were the subject of investigation. Two polymers were examined, one is an alternating co-polymer (P1) in which the guanidinium groups are on every other repeat unit and the second is a homopolymer with the guanidinium groups on every repeat unit. The photophysical properties of the CPEs were investigated in CH3OH and H2O solution by absorption, steady-state fluorescence and fluorescence lifetime spectroscopy. The results indicate that P1 and P2 are molecularly dissolved in CH3OH solution; however, in water the polymers aggregate as evidenced by a substantial reduction in the fluorescence yield. Addition of the non-ionic surfactant (Triton X-100) into the weakly fluorescent aqueous solution of P1 increased the fluorescence by forming a polymer/surfactant complex. The fluorescence of the polymer/surfactant complex in aqueous solution was effectively quenched by the addition of pyrophosphate (PPi) with Stern-Volmer quenching constants (K(sv)) ∼ 1.7 × 10(5) M(-1); the quenching occurs because PPi binds to the guanidinium groups and induces the aggregation of the polymer/surfactant complex. In addition, by using fluorescence correlation spectroscopy it was found that the diffusion time of the aggregated complex is increased 9-fold in comparison with the free CPE/surfactant complex. A sensor is developed utilizing the significant changes in fluorescence induced by the addition of PPi.


Presynaptic GABAB receptors functionally uncouple somatostatin interneurons from the active hippocampal network.
Information processing in cortical neuronal networks relies on properly balanced excitatory and inhibitory neurotransmission. A ubiquitous motif for maintaining this balance is the somatostatin interneuron (SOM-IN) feedback microcircuit. Here, we investigated the modulation of this microcircuit by presynaptic GABAB receptors (GABABRs) in the rodent hippocampus. Whole-cell recordings from SOM-INs revealed that both excitatory and inhibitory synaptic inputs are strongly inhibited by GABABRs, while optogenetic activation of the interneurons shows that their inhibitory output is also strongly suppressed. Electron microscopic analysis of immunogold-labelled freeze-fracture replicas confirms that GABABRs are highly expressed presynaptically at both input and output synapses of SOM-INs. Activation of GABABRs selectively suppresses the recruitment of SOM-INs during gamma oscillations induced in vitro. Thus, axonal GABABRs are positioned to efficiently control the input and output synapses of SOM-INs and can functionally uncouple them from local network with implications for rhythmogenesis and the balance of entorhinal versus intrahippocampal afferents.


A clinical prediction rule for identifying patients with patellofemoral pain who are likely to benefit from foot orthoses: a preliminary determination.
To develop a clinical prediction rule to identify patients with patellofemoral pain (PFP) who are more likely to benefit from foot orthoses. Posthoc analysis of one treatment arm of a randomised clinical trial. Single-centre trial in a community setting in Brisbane, Australia. 42 participants (mean age 27.9 years) with a clinical diagnosis of PFP (median duration 36 months). Foot orthoses fitted by a physiotherapist. Five-point global improvement scale at 12-week follow-up, dichotomised with marked improvement equalling success. Potential predictor variables identified by univariate analyses were age, height, pain severity, anterior knee pain scale score, functional index questionnaire score, foot morphometry (arch height ratio, mid-foot width difference from non-weight bearing to weight bearing) and overall orthoses comfort. Parsimonious fitting of these variables to a model that explained success with orthoses identified the following: age (>25 years), height (<165 cm), worst pain visual analogue scale (<53.25 mm) and a difference in mid-foot width from non-weight bearing to weight bearing (>10.96 mm). The pretest success rate of 40% increased to 86% if the patient exhibited three of these variables (positive likelihood ratio 8.8; 95% CI 1.2 to 66.9). Post-hoc analysis identified age, height, pain severity and mid-foot morphometry as possible predictors of successful treatment of PFP with foot orthoses, thereby providing practitioners with information for prescribing foot orthoses in PFP and stimulating further research.


A Review of Gelatin Source Authentication Methods.
Gelatin is a very popular pharmaceutical and food ingredient and the most studied ingredient in Halal researches. Interest in source gelatin authentication is based on religious and cultural beliefs, food fraud prevention and health issues. Seven gelatin authentication methods that have been developed include: nucleic acid based, immunochemical, electrophoretic analysis, spectroscopic, mass-spectrometric, chromatographic-chemometric and chemisorption methods. These methods are time consuming, and require capital intensive equipment with huge running cost. Reliability of gelatin authentication methods is challenged mostly by transformation of gelatin during processing and close similarities among gelatin structures. This review concisely presents findings and challenges in this research area and suggests needs for more researches on development of rapid authentication method and process-transformed gelatins.


Toward Prevention of Mild Cognitive Impairment in Older Adults With Depression: An Observational Study of Potentially Modifiable Risk Factors.
Late-life depression has been associated with increased risk of mild cognitive impairment (MCI) and dementia. Predictors of increased risk are incompletely understood. Identification of potentially modifiable risk factors could facilitate prevention of MCI and dementia. This study aimed to determine which clinical characteristics are associated with increased risk of MCI among older adults with depression and normal cognition at baseline. Data from the National Alzheimer's Coordinating Center dataset were used. Study participants who attended a participating Alzheimer's Disease Center from September 2005 through September 2017 with normal cognition and a history of clinically defined depression (broadly based on DSM criteria) were followed until first diagnosis of MCI (or dementia when MCI was not diagnosed). A total of 2,655 study participants were followed for a median duration of 41.8 months. Of these, 586 (22.1%) developed either MCI (n = 509, 19.2%) or dementia (n = 77, 2.9%). In survival analyses, cognitive decline was associated with age, sex, education, baseline cognition, and several potentially modifiable risk factors including vascular risk factors, hearing impairment, vitamin B₁₂ deficiency, active depression within the last 2 years, and increased severity of depression. In an adjusted survival analysis, the only variables that remained significantly associated with development of MCI or dementia were female sex (HR = 0.72; 95% CI, 0.59-0.88), higher education (HR = 0.96; 95% CI, 0.93-0.99), and higher baseline cognition (HR = 0.87; 95% CI, 0.82-0.93), which were associated with reduced risk, and older age (HR = 1.07; 95% CI, 1.05-1.08), active depression within the last 2 years (HR = 1.41; 95% CI, 1.15-1.74), and increased severity of depression (HR = 1.05; 95% CI, 1.02-1.09), which were associated with increased risk. Development of MCI is associated with several potentially modifiable risk factors in older adults with depression. Future studies should determine whether active management of risk factors could reduce incidence of MCI in this vulnerable population.


In situ dividing and phagocytosing retinal microglia express nestin, vimentin, and NG2 in vivo.
Following injury, microglia become activated with subsets expressing nestin as well as other neural markers. Moreover, cerebral microglia can give rise to neurons in vitro. In a previous study, we analysed the proliferation potential and nestin re-expression of retinal macroglial cells such as astrocytes and Müller cells after optic nerve (ON) lesion. However, we were unable to identify the majority of proliferative nestin(+) cells. Thus, the present study evaluates expression of nestin and other neural markers in quiescent and proliferating microglia in naïve retina and following ON transection in adult rats in vivo. For analysis of cell proliferation and cells fates, rats received BrdU injections. Microglia in retinal sections or isolated cells were characterized using immunofluorescence labeling with markers for microglia (e.g., Iba1, CD11b), cell proliferation, and neural cells (e.g., nestin, vimentin, NG2, GFAP, Doublecortin etc.). Cellular analyses were performed using confocal laser scanning microscopy. In the naïve adult rat retina, about 60% of resting ramified microglia expressed nestin. After ON transection, numbers of nestin(+) microglia peaked to a maximum at 7 days, primarily due to in situ cell proliferation of exclusively nestin(+) microglia. After 8 weeks, microglia numbers re-attained control levels, but 20% were still BrdU(+) and nestin(+), although no further local cell proliferation occurred. In addition, nestin(+) microglia co-expressed vimentin and NG2, but not GFAP or neuronal markers. Fourteen days after injury and following retrograde labeling of retinal ganglion cells (RGCs) with Fluorogold (FG), nestin(+)NG2(+) microglia were positive for the dye indicating an active involvement of a proliferating cell population in phagocytosing apoptotic retinal neurons. The current study provides evidence that in adult rat retina, a specific resident population of microglia expresses proteins of immature neural cells that are involved in injury-induced cell proliferation and phagocytosis while transdifferentiation was not observed.


Cardiovascular complications of cocaine: imaging findings.
Cocaine is the second most commonly abused illicit drug in the US and the most common one involved in emergency department visits, the majority of which are related to the cardiovascular system. Cardiovascular complications related with cocaine abuse include myocardial ischemia and infarction, myocarditis, hypertrophic cardiomyopathy, dilated cardiomyopathy, aortic dissection, thrombosis, stroke and cerebral hemorrhage, and different forms of visceral ischemia, among others. In an era where cocaine use has reached epidemic proportions, it is necessary for the radiologist to understand the pathophysiology, clinical presentation, and imaging characteristics of its cardiovascular complications.


Personalized cancer medicine: molecular diagnostics, predictive biomarkers, and drug resistance.
The progressive elucidation of the molecular pathogenesis of cancer has fueled the rational development of targeted drugs for patient populations stratified by genetic characteristics. Here we discuss general challenges relating to molecular diagnostics and describe predictive biomarkers for personalized cancer medicine. We also highlight resistance mechanisms for epidermal growth factor receptor (EGFR) kinase inhibitors in lung cancer. We envisage a future requiring the use of longitudinal genome sequencing and other omics technologies alongside combinatorial treatment to overcome cellular and molecular heterogeneity and prevent resistance caused by clonal evolution.


On the high frequency transfer of mechanical stimuli from the surface of the head to the macular neuroepithelium of the mouse.
Vestibular macular sensors are activated by a shearing motion between the otoconial membrane and underlying receptor epithelium. Shearing motion and sensory activation in response to an externally induced head motion do not occur instantaneously. The mechanically reactive elastic and inertial properties of the intervening tissue introduce temporal constraints on the transfer of the stimulus to sensors. Treating the otoconial sensory apparatus as an overdamped second-order mechanical system, we measured the governing long time constant (Τ(L)) for stimulus transfer from the head surface to epithelium. This provided the basis to estimate the corresponding upper cutoff for the frequency response curve for mouse otoconial organs. A velocity step excitation was used as the forcing function. Hypothetically, the onset of the mechanical response to a step excitation follows an exponential rise having the form Vel(shear) = U(1-e(-t/TL)), where U is the applied shearing velocity step amplitude. The response time of the otoconial apparatus was estimated based on the activation threshold of macular neural responses to step stimuli having durations between 0.1 and 2.0 ms. Twenty adult C57BL/6 J mice were evaluated. Animals were anesthetized. The head was secured to a shaker platform using a non-invasive head clip or implanted skull screws. The shaker was driven to produce a theoretical forcing step velocity excitation at the otoconial organ. Vestibular sensory evoked potentials (VsEPs) were recorded to measure the threshold for macular neural activation. The duration of the applied step motion was reduced systematically from 2 to 0.1 ms and response threshold determined for each duration (nine durations). Hypothetically, the threshold of activation will increase according to the decrease in velocity transfer occurring at shorter step durations. The relationship between neural threshold and stimulus step duration was characterized. Activation threshold increased exponentially as velocity step duration decreased below 1.0 ms. The time constants associated with the exponential curve were Τ(L) = 0.50 ms for the head clip coupling and T(L) = 0.79 ms for skull screw preparation. These corresponded to upper -3 dB frequency cutoff points of approximately 318 and 201 Hz, respectively. T(L) ranged from 224 to 379 across individual animals using the head clip coupling. The findings were consistent with a second-order mass-spring mechanical system. Threshold data were also fitted to underdamped models post hoc. The underdamped fits suggested natural resonance frequencies on the order of 278 to 448 Hz as well as the idea that macular systems in mammals are less damped than generally acknowledged. Although estimated indirectly, it is argued that these time constants reflect largely if not entirely the mechanics of transfer to the sensory apparatus. The estimated governing time constant of 0.50 ms for composite data predicts high frequency cutoffs of at least 318 Hz for the intact otoconial apparatus of the mouse.


Investigation of complex canopies with a functional-structural plant model as exemplified by leaf inclination effect on the functioning of pure and mixed stands of wheat during grain filling.
Because functional-structural plant models (FSPMs) take plant architecture explicitly into consideration, they constitute a promising approach for unravelling plant-plant interactions in complex canopies. However, existing FSPMs mainly address competition for light. The aim of the present work was to develop a comprehensive FSPM accounting for the interactions between plant architecture, environmental factors and the metabolism of carbon (C) and nitrogen (N). We developed an original FSPM by coupling models of (1) 3-D wheat architecture, (2) light distribution within canopies and (3) C and N metabolism. Model behaviour was evaluated by simulating the functioning of theoretical canopies consisting of wheat plants of contrasting leaf inclination, arranged in pure and mixed stands and considering four culm densities and three sky conditions. As an emergent property of the detailed description of metabolism, the model predicted a linear relationship between absorbed light and C assimilation, and a curvilinear relationship between grain mass and C assimilation, applying to both pure stands and each component of mixtures. Over the whole post-anthesis period, planophile plants tended to absorb more light than erectophile plants, resulting in a slightly higher grain mass. This difference was enhanced at low plant density and in mixtures, where the erectophile behaviour resulted in a loss of competitiveness. The present work demonstrates that FSPMs provide a framework allowing the analysis of complex canopies such as studying the impact of particular plant traits, which would hardly be feasible experimentally. The present FSPM can help in interpreting complex interactions by providing access to critical variables such as resource acquisition and allocation, internal metabolic concentrations, leaf life span and grain filling. Simulations were based on canopies identically initialized at flowering; extending the model to the whole cycle is thus required so that all consequences of a trait can be evaluated.


Effect of delapril/manidipine vs olmesartan/ hydrochlorothiazide combination on insulin sensitivity and fibrinogen in obese hypertensive patients.
To compare the effect of delapril/manidipine vs olmesartan/hydrochlorothiazide (HCTZ) combination on insulin sensitivity and plasma fibrinogen in obese hypertensive patients. After a 4-week placebo period, 88 obese, hypertensive (DBP >95 and <110 mmHg) outpatients were randomized to delapril 30 mg/manidipine 10 mg combination or to olmesartan 20 mg/HCTZ 12.5 mg combination for 24 weeks according to a prospective, randomized, open-label, blinded endpoint, parallel group design. At the end of the placebo period and treatment period, clinical BP, fasting plasma glucose (FPG), plasma insulin, insulin sensitivity (by euglycemic hyperinsulinemic clamp) and plasma fibrinogen were evaluated. Insulin sensitivity was expressed as the amount of glucose infused during the last 30 minutes (glucose infusion rate, GIR) in mg/Kg/min. The total glucose requirement (TGR) to maintain a steady-state blood glucose level in response to a defined increase in plasma insulin concentration was also evaluated. Both combinations significantly reduced SBP/DBP values (-22.3/16.4 mmHg and -22.6/17.2 mmHg, respectively, all p <0.001 vs placebo). GIR was significantly increased only by delapril/manidipine (+3.01 mg/min/Kg, p=0.038 vs placebo), the difference between treatments being significant (p <0.05). TGR was significantly increased by delapril/manidipine (+9.7 g, p=0.034), while it was unaffected by olmesartan/HCTZ. Plasma insulin as well as fibrinogen were significantly reduced by delapril/manidipine (-17.8 pmol/l, p=0.047 and -67.5 mg/dl, p=0.021, respectively), but not by olmesartan/HCTZ, the difference between the two treatments being statistically significant (p <0.05). In obese hypertensive patients the delapril/manidipine combination but not the olmesartan/HCTZ combination significantly decreased insulin resistance and plasma fibrinogen levels, despite the similar BP lowering efficacy.


Radiotherapy for patients with stage IV classical Hodgkin lymphoma: a propensity-matched analysis of the surveillance, epidemiology, and end results database.
Background The survival advantage of radiotherapy for patients with stage IV classic Hodgkin lymphoma (HL) has not been adequately evaluated. Methods We analyzed patients with stage IV HL enrolled from the Surveillance, Epidemiology, and End Results (SEER) registry from January 2000 to December 2012. Propensity score (PS) analysis with 1:2 matching was performed to ensure well-balanced characteristics of the comparison groups. Kaplan-Meier and Cox proportional hazardous model were used to evaluate the overall survival (OS), cancer-specific survival (CSS), the hazards ratio (HR) and corresponding 95% confidence intervals (95% CI). Results Overall, for all patients with stage IV HL, receiving radiotherapy was associated with both significantly improved OS and CSS. Radiotherapy to any lesions could independently improve the OS and CSS by 30% to 36% in the multivariate analyses before and after PS matching (PSM), with the best improvement of 33% to 40% observed for patients with nodular sclerosis (P < 0.05) among all HL pathological types. In particular, radiotherapy, most likely to the residual site, was more pronouncedly associated with the improvement in survival for patients with stage IV HL who were young (age<45, P < .05) or without B symptoms (PInteraction for OS = 0.099, PInteraction for CSS = 0.255). For those patients without B symptoms, after PSM, the OS was improved by 65% (P = .021). Conclusions The large SEER results support that radiotherapy is associated with better survival of patients with stage IV HL.


New species and records of Trichoderma isolated as mycoparasites and endophytes from cultivated and wild coffee in Africa.
A survey for species of the genus Trichoderma occurring as endophytes of Coffea, and as mycoparasites of coffee rusts (Hemileia), was undertaken in Africa; concentrating on Cameroon and Ethiopia. Ninety-four isolates of Trichoderma were obtained during this study: 76 as endophytes of healthy leaves, stems and berries and, 18 directly from colonized rust pustules. A phylogenetic analysis of all isolates used a combination of three genes: translation elongation factor-1α (tef1), rpb2 and cal for selected isolates. GCPSR criteria were used for the recognition of species; supported by morphological and cultural characters. The results reveal a previously unrecorded diversity of Trichoderma species endophytic in both wild and cultivated Coffea, and mycoparasitic on Hemileia rusts. Sixteen species were delimited, including four novel taxa which are described herein: T. botryosum, T. caeruloviride, T. lentissimum and T. pseudopyramidale. Two of these new species, T. botryosum and T. pseudopyramidale, constituted over 60% of the total isolations, predominantly from wild C. arabica in Ethiopian cloud forest. In sharp contrast, not a single isolate of Trichoderma was obtained using the same isolation protocol during a survey of coffee in four Brazilian states, suggesting the existence of a 'Trichoderma void' in the endophyte mycobiota of coffee outside of Africa. The potential use of these African Trichoderma isolates in classical biological control, either as endophytic bodyguards-to protect coffee plants from Hemileia vastatrix, the fungus causing coffee leaf rust (CLR)-or to reduce its impact through mycoparasitism, is discussed, with reference to the on-going CLR crisis in Central America.


NFAT expression in human osteoclasts.
Nuclear factor of activated T-cells cytoplasmic (NFATc) is a family of transcription factors originally identified in T-cells. The gene family is currently known to have four members (NFATc1 through NFATc4) which have roles both within and outside the immune system. We show that NFATc1 is the major induced NFAT in human osteoclasts, with expression greatly exceeding that of NFATc2 through NFATc4. In macrophage-like cells in culture, NFATc1 through NFATc4 are expressed at similar low levels. NFATc1 is comprised of five mRNA transcript variants known to encode three different protein isoforms. The mRNA encoding isoform C (mRNA variant 3) was the most expressed with 38 copies per nanogram followed by isoform B (mRNA variant 5) with 17 copies per nanogram of total RNA. Isoform A (mRNA variant 1) and mRNA variants 2 and 4 made up less than 1% of the total NFATc1 expressed. NFATc1 is activated by calcineurin after calcium-calmodulin signalling. The induction of NFATc1 in osteoclasts was not altered in the presence of cyclosporin A, an inhibitor of calcineurin, suggesting that NFATc1 does not participate in autoregulatory activation of its own promoter. The NFATc1 variants expressed by human osteoclasts are not those normally expressed by effector T-cells but are similar to those seen in naïve T-cells.


USP2 inhibition prevents infection with ACE2-dependent coronaviruses in vitro and is protective against SARS-CoV-2 in mice.
Targeting angiotensin-converting enzyme 2 (ACE2) represents a promising and effective approach to combat not only the COVID-19 pandemic but also potential future pandemics arising from coronaviruses that depend on ACE2 for infection. Here, we report ubiquitin specific peptidase 2 (USP2) as a host-directed antiviral target; we further describe the development of MS102, an orally available USP2 inhibitor with viable antiviral activity against ACE2-dependent coronaviruses. Mechanistically, USP2 serves as a physiological deubiquitinase of ACE2, and targeted inhibition with specific small-molecule inhibitor ML364 leads to a marked and reversible reduction in ACE2 protein abundance, thereby blocking various ACE2-dependent coronaviruses tested. Using human ACE2 transgenic mouse models, we further demonstrate that ML364 efficiently controls disease caused by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), as evidenced by reduced viral loads and ameliorated lung inflammation. Furthermore, we improved the in vivo performance of ML364 in terms of both pharmacokinetics and antiviral activity. The resulting lead compound, MS102, holds promise as an oral therapeutic option for treating infections with coronaviruses that are reliant on ACE2.


[Non-steady state kinetics for action of a multienzyme cellulase system toward insoluble cellulose].
A kinetic theory for multienzyme cellulase systems in non-steady state conditions (in relation to intermediate metabolites) of hydrolysis of insoluble cellulose has been developed. To verify the kinetic regularities obtained the action of 12 different cellulases from the fungi Trichoderma, Geotrichum and Aspergillus as well as from bacterial cells Thermomonospora sp. and Rapidase preparation has been studied with respect to ball milled cotton linters and microcrystalline cellulose. The experimental data were discussed in the framework of mechanism of enzymatic hydrolysis of cellulose suggest by us recently and the main routes for glucose and cellobiose formation from insoluble cellulose have been elucidated. The effects of concentrations of cellulase preparations and the initial substrate on (i) time lags for glucose formation, (ii) stationary rate of glucose formation, and (iii) kinetics of cellulose conversion to glucose at low and high conversion degrees, were studied. A theoretical analysis of maxima and inflection points on the kinetic curves for intermediates (oligosaccharides and cellobiose) was performed. The effects and intensity of stirring on the time lag values for glucose formation were studied and the relative role of kinetic and diffusional factors in this process was evaluated. The data obtained are unequivocally indicative of the common mechanism of conversion of cellulose to glucose by cellulase complexes irrespective of their source and composition.


High-Resolution Metalens Imaging with Sequential Artificial Intelligence Models.
An analysis of the optical response of a GaN-based metalens was conducted alongside the utilization of two sequential artificial intelligence (AI) models in addressing the occasional issues of blurriness and color cast in captured images. The optical loss of the metalens in the blue spectral range was found to have resulted in the color cast of images. Autoencoder and CodeFormer sequential models were employed in order to correct the color cast and reconstruct image details, respectively. Said sequential models successfully addressed the color cast and reconstructed details for all of the allocated face image categories. Subsequently, the CIE 1931 chromaticity diagrams and peak signal-to-noise ratio analysis provided numerical evidence of the AI models' effectiveness in image reconstruction. Furthermore, the AI models can still repair the image without blue information. Overall, the integration of metalens and artificial intelligence models marks a breakthrough in enhancing the performance of full-color metalens-based imaging systems.